The Great Resignation — Managing the Impact on Research Teams
Among other things, 2021 will be known as the year of The Great Resignation, or in many sectors, the great retirement. Record numbers of employees left their jobs. Nearly four and a half million Americans left their jobs in September 2021, the highest number on record since the Bureau of Labor Statistics began collecting data 20 years ago. The numbers show a 40 percent increase over the same period in 2020.
The healthcare sector has not been spared. According to the report, 589,000 U.S. workers resigned or retired from health care and social assistance positions. A children’s hospital in Ohio recently put out a call for clinical volunteers to help support staffing shortages. A study in Utah in April that tested the sentiments of nearly 28,000 University of Utah Health system clinical and non-clinical faculty, staff and trainees found that 20 percent of respondents, 1 in 5, are considering leaving their professions.
Economists and pundits are untangling the possible reasons for this massive change in the labor market. Some suggest The Great Resignation is driven by massive burnout among workers. Others point to stagnant wages, lack of career growth opportunities, and challenging work conditions. Yet others suggest that employees who have been working from home simply do not want to return to the office and prefer the flexibility offered during the pandemic.
The trend may continue. A recent Gallup survey found that 48 percent of the working population in the United States is actively job searching. Studies show that the trend is driven by mid-career employees — those between 30 and 45 years old as well as those close to retirement age that decided to retire after the height of the pandemic. This can suggest a loss of critical experience and expertise, in addition to the drop in engagement and productivity.
Recruiting, hiring, and training new research staff is expensive and time-consuming. This effort may impact the ability of research sites’ to manage current clinical trials or even start new trials in 2022. The disruption in staffing also may pose risks, since much of the work requires a fine-tuned attention to detail that may be lost as staff including coordinators, research nurses, and principal investigators transition to roles outside of research or move to other organizations.
To mitigate these risks, leaders must address employee disengagement on multiple fronts — long-term and short-term. In the long term, research leaders need to evaluate how to retain and engage experienced workers to minimize turnover. In the short term, workers must be protected from overwork and potential burnout, and offered the opportunity to engage in meaningful work with flexibility.
To achieve this, research administrators and leaders can consider these strategies:
- Increase learning opportunities — Beyond the required training and certifications for clinical research coordinators and other staff, leaders should provide additional online learning opportunities. A June 2021 survey with Amazon, Gallup found that 57 percent of U.S. workers want to update their skills and 48 percent would consider switching jobs to do it.
Advanced training and “upskilling” can include courses in project management for clinical trials; preventing and identifying misconduct and noncompliance; financial management of clinical trials; subject recruitment and retention; statistics and data management of clinical trials; and specialty areas including regulatory compliance.
- Cultivate career development — The same Gallup study showed that the primary reason people change jobs is for career growth opportunities. Training can position early-career staff for additional responsibilities, which then provides research sites with a deeper bench of talent for advancement.
Managing clinical trials requires many administrative tasks that, while important, may be less professionally fulfilling. Having a clearly communicated path for career growth and advancement can incentivize employees to stay.
- Create flexible work environments — Starting and running clinical trials requires a high degree of staffing flexibility as workloads shift. Outsourcing the administrative burden can enable site staff to focus on strategic needs while filling in short-term gaps. The result can be more efficient resource management and consistency in research infrastructure.
The Great Resignation of 2021 shows no signs of slowing in the new year. Research sites must create and nurture environments for employee career growth and engagement to remain competitive.
The Future of Work and the Impact on Research Institutions
International organizations such as the World Economic Forum have been researching and analyzing the “future of work” and its implications for economies. Likewise, consulting firms have been predicting the important training needed to prepare workforces for new labor markets. Surveys of company leaders indicate an increasing need for employee upskilling and retraining.
The COVID pandemic and dizzying changes to our work environments accelerated the already-occurring changes in how we work. For research professionals, the changes have impacted how we start-up and manage clinical trials. The breakneck speed with which pharmaceutical companies developed, tested, and deployed COVID vaccines may have been a preview. The clinical trial community should understand the lessons learned from these expedited processes and consider how to prepare for “the next time.”
It remains to be seen which changes will remain for the long term. But some experts say that some permanent changes are inevitable, whether it’s remote patient visits, online collaboration, or remote digital monitoring.
Studies about the future of work tend to focus on the use of artificial intelligence and increased dependency on automation. There are human factors to consider, as well. Managers must define how to run hybrid teams and encourage resilience among workers. The World Economic Forum identifies major changes in three categories:
- Technology in the form of machine learning, artificial intelligence, and automation
- Ongoing learning and skill acquisition
- Talent mobility
This was supported by a report by McKinsey & Company, published in October 2020, that said workers in the life sciences had to double their efforts to focus on patients, leverage technology, and cultivate workplace agility.
Flexible work force
The ability to accommodate the ebb and flow of clinical research activities, or rapid redeployment based on shifting priorities, means that leaders need flexible staffing.
Hybrid work situations will require the need for cross-training among staff and the increased use of external resources to supplement internal staff. Highly responsive teams, augmented by expert hands-on external staff, can ensure sustainability of existing research projects even when new or urgent needs emerge.
Improving patient communication
The requirement to obtain informed consent of individuals before involving them in research is one of the central protections provided for under the HHS regulations at 45 CFR part 46 and 21 CFR 50.
The Revised Common Rule introduced new informed consent standards that focus on providing prospective research participants with information that a reasonable person would want to have in order to make an informed decision about participation in a research study. Additionally, the presentation of information to the participant must be organized and include sufficient detail to facilitate the participants understanding of why they may or may not want to join the research study.
These requirements, along with the shift to e-consent and other technologies, have changed not only the language of consent forms but also the process and workflow in obtaining consent.
This is just one example of many patient-centered shifts in the paradigm of clinical research.
Beyond the required certifications in Good Clinical Practice or foundations for clinical research coordinators, research institutions must offer ongoing upskilling opportunities for staff to keep them up-to-date on the shifting technology and regulatory landscapes of clinical research.
Even prior to the pandemic, online learning was dominating the professional development field. Hiring managers who wanted to cultivate a more diverse and agile workforce were using online solutions such as CITI Program to ensure their skills were up to date.
Leveraging technology for better collaboration and improved workflow
Writing a protocol for a clinical trial has become a complex team sport requiring multidisciplinary input from various sources. Researchers are collaborating with colleagues at their own or other institutions, across clinical disciplines.
The protocol-writing process — from version management to IRB review — can be cumbersome. The use of paper-based systems, or even email, can result in confusion or delays. The result can mean incomplete IRB submissions and frustration for investigators.
Cloud-based guided applications, such as Protocol Builder, can expedite the process by fostering communication and teamwork. These systems build teaching into the writing process, which is essential for residents or new investigators. A complete and compliant protocol submission can result in a smoother IRB review process.
While no one has a crystal ball into the future, many organizations and foresight consultants are in general agreement that the workplace is undergoing a paradigm shift. Research institutions are not immune to these major changes, particularly if they focus on the key areas of change — mobility and flexibility, increased use of technology, and ongoing learning and upskilling.
NIH Announces Consortium to Streamline Gene Therapy Research
The National Institutes of Health (NIH) announced this week that they were joining forces with the Food and Drug Administration (FDA), ten pharmaceutical companies and five non-profit organizations to accelerate the development of gene therapies for rare diseases. The new public-private partnership, called the Bespoke Gene Therapy Consortium, aims to overcome obstacles and streamline the process of developing therapies that could treat diseases that collectively impact millions of people.
The consortium will fund basic and clinical research from a five-year budget of $76 million. This represents an opportunity for investigators. For institutions interested in participating in the expected clinical trials, it may be time to revisit their policies for biosafety and gene transfer. Institutional Biosafety Committees (IBC) are required at institutions that conduct NIH-funded recombinant DNA, or gene therapy, research.
An IBC is concerned for the protection of not only research subjects, but also staff and communities in which the research takes place. The committee has oversight for establishing, monitoring, and enforcing policies and procedures for handling biohazardous materials, such as recombinant DNA.
An IBC works in parallel with an Institutional Review Board (IRB), with special attention to risk assessment for areas including:
- Study agent
- Containment levels and procedures required to safely handle the study agent
- Preparedness of the facility and its personnel
- Potential impact to the environment
Activities of the IBC include:
- Review agent characteristics (e.g. virulence, pathogenicity, environmental stability)
- Determining the appropriate biosafety level for physical and biological containment, as required by the NIH Guidelines
- Inspection of facilities, procedures, and practices
- Evaluating the training and experience of the personnel involved in the research
- Confirming appropriate policies and procedures are in place for handling spills or accidents to minimize exposure to or contamination from any potentially hazardous material
- Reporting significant events or violations to regulatory authorities including NIH and institutional officials
- File an annual report with the NIH
NIH requires that an IBC have at least five members who collectively have broad experience and expertise that allows them to conduct such assessments. This may include members with technical expertise in potentially hazardous biological materials, human research protocols, regulatory requirements, and in the health and protection of the community and environment. Additionally, at least two members must be unaffiliated with the organization conducting the research, and these members should represent the interest of the surrounding community with respect to health and protection of the environment.
The establishment and funding of the Bespoke Gene Therapy Consortium will increase the opportunity for investigators to participate in basic and clinical research to address significant unmet medical needs of patients. The safe conduct of experiments involving recombinant or synthetic nucleic acid molecules depends on the individual conducting such activities, as well as having appropriate safety mechanisms at the institutional level.
BRANY offers IBC services that can help expedite the review of research that involves recombinant DNA (“rDNA”) or synthetic nucleic acid molecules, or DNA or RNA derived from recombinant or synthetic nucleic acid molecules, providing rigorous biosafety oversight so that institutions can focus their efforts on scientific research and advancement. Contact us for more information.
FDA Updates Guidance for Clinical Trials During COVID-19 Pandemic
In March 2020, as governments around the world were issuing large-scale lockdowns, health facilities shifted their efforts to addressing critical needs of patients while trying to maintain the safety of staff. Clinical trials ended or were paused, and researchers allocated their attention and resources to understanding and managing the novel coronavirus.
To assist researchers, IRBs, and sponsors, the FDA issued guidance last year on the conduct of clinical trials during the COVID-19 pandemic. The guidance aimed to help institutions protect clinical trial participants, maintain compliance with Good Clinical Practice, and ensure data integrity of the research. Among the many challenges brought on by COVID-19, some of the most vexing logistical challenges came from quarantines, site closures, travel limitations, and interruptions of the supply chain for investigational or other products. In addition, institutional leaders have had to address considerations if site personnel or trial participants became infected with COVID-19.
The FDA recently updated this guidance, in August 2021. This is a high-level review of some of the issues addressed in the guidance.
Deviations from a protocol may be necessitated by changes to public health recommendations both at the national and local levels. Also, deviations can occur in the case of exposure, a positive test, or diagnosis of a trial participant.
Deviations can include a change in how patients are monitored — from in-person to remote visits, for example. COVID-19 has increased the acceptance of these alternative methods of monitoring, reducing unnecessary travel and risk of exposure for participants. For the safety of participants, sponsors may consider options such as phone calls, virtual visits, or even remote monitoring devices.
Some changes to the protocol or investigational plan are intended to minimize or eliminate immediate hazards or to protect the life and well-being of research participants. In these urgent cases, deviations may be implemented without IRB approval or before filing an amendment to the investigational new drug (IND) or investigational device exemption (IDE) However, they are required to be reported afterwards.
Investigators should work closely with IRBs to ensure policies and regulatory requirements for reporting deviations are followed and, when needed, develop plans or procedures to prioritize reporting of deviations that may impact the safety of trial participants.
Additional Screening Procedures
Institutions may require COVID-19 screening of clinical trial participants. In these cases, the screening does not need to be reported as an amendment to the protocol, even if done during clinical study visits.
On the other hand, if the sponsor is incorporating the data collected as part of a new research objective, it should be reported as a change to the protocol. This additional protocol-driven screening should also be considered in the clinical trial budgeting process.
The Importance of Documentation
Sponsors and clinical investigators should document how restrictions related to COVID-19 led to the changes in study conduct and duration of those changes. They should indicate which trial participants were impacted, and how those trial participants were impacted.
Some changes, such as an adjustment in a study visit schedule, may lead to missing information. In those cases, it is important to capture in the case report what specific data is missing and the reason for its absence.
Other items that sponsors should document:
- Contingency measures implemented to manage disruptions due to COVID-19
- A list of all participants who were impacted by COVID-19-related study disruptions, and how they were impacted
- Analysis of how contingency measures may have impacted safety and efficacy results
Protecting Data Integrity
Sponsors that anticipate that changes to the protocol will impact data management procedures or statistical analysis plans should coordinate with their respective FDA review division. This includes situations in which the efficacy endpoints may be impacted. For example, assessments may be conducted virtually instead of in-person. Any modifications to the data management or statistical analysis plan but also receive IRB review and approval.
Questions and Answers
The guidance also contains an appendix with 28 questions along with detailed answers for each question. Some of the topics covered include:
- re-monitoring after pandemic related restrictions are lifted
- exclusion criteria for “investigational medical products”
- collecting electronic signatures and Part 11 compliance
- reviewing IND safety reports
Twenty months after the first COVID-19 case was confirmed in the United States, researchers are still trying to understand the long-term impact on non-COVID clinical trials. Researchers and clinical trial professionals have had to demonstrate resilience, flexibility, and adaptation in the face of uncertainty and a changing epidemiological landscape.
The primary guiding principle throughout the guidance is to ensure the safety of clinical trial participants.
Coverage Analysis for Investigational Device Exemption (IDE) Studies
A Medicare coverage analysis (MCA) for clinical trials evaluates which tests, procedures, and interventions will be associated with a clinical trial. This analysis results in a budget and plan for invoicing third party payers and sponsors. Clinical trials for devices differ from interventional trials for drugs in a few key ways that can impact the process of conducting a coverage analysis.
While drug trials often involve a local review by the institution to document the qualification of a clinical trial, device trials with an FDA letter dated effective January 1, 2015, are reviewed at the national level by CMS. Prior to this change, devices with an FDA letter dated prior to January 1, 2015, sponsors and sites had to wait for IRB approvals and fully executed agreements in order to submit documents to the local Medicare contractor.
Medicare authorizes payment of the routine costs of care furnished to its beneficiaries in certain categories of Investigational Device Exemption (IDE) studies. However, there are a few items that Medicare excludes. These includes costs for items:
- paid for by the sponsor
- identified as free in the informed consent document
- not ordinarily covered by Medicare
- solely to determine trial eligibility or for data collection or analysis
The CMS approval process applies to category A and B trials. The category of the device, as assigned by the FDA, determines what is reimbursed by Medicare.
- Category A devices are experimental or novel. Medicare will cover only the routine costs of care, but not the device itself.
- Category B devices are non-experimental, or a similar device may already be in the marketplace. Medicare may cover the costs of care and the device.
To identify the “routine costs of care,” it is important to understand the protocol in detail. Devices may require surgical interventions that include a hospital stay, thus complicating the billing process. Analysts must review the ICD billing codes that may be referenced, including both hospital and professional fees.
To be considered for coverage, CMS requires documentation that covers similar issues as a drug intervention trial. CMS requires the submission packet to include:
- Request letter that describes the scope and nature of the study
- Complete FDA approval letter for your Category A or B IDE
- IDE study protocol that includes descriptions CMS wants to see:
- Method and timing of release of results on all prespecified outcomes, including release of negative outcomes and that the release should be hastened if the study is terminated early
- How Medicare beneficiaries may be affected by the device under investigation
- How study results are or are not expected to be generalizable to the Medicare beneficiary population
- Institutional Review Board (IRB) approval letter
- The National Clinical Trial (NCT) number
- Any supporting materials
The sponsor may sometimes submit the packet to CMS for reimbursement. After that, the investigator or study site should be in contact with their Regional Medicare Administrator (MAC) to receive acknowledgement of receipt and receive further information on obtaining billing and coding information.
CMS does not provide detail about which clinical items are approved for reimbursement. Despite receiving CMS approval for an IDE study, sites are accountable for negotiating the contract with the sponsor and for billing appropriately. An accurate and detailed coverage analysis ensures correct billing and avoids costly financial errors. More importantly, it reduces the risk of non-compliant billing, which can have significant negative repercussions. The analysis is an essential component of a study start-up process and conducting it in a timely way can avoid start-up delays.
Medicare Coverage Related to Investigational Device Exemption (IDE) Studies (CMS)
Be Prepared for an FDA Audit
An FDA audit or inspection can occur at any time, and sometimes with very little advance warning. The FDA conducts both announced and unannounced inspections of clinical investigator sites, typically under the following circumstances:
- to verify the accuracy and reliability of data that has been submitted to the agency;
- as a result of a complaint to the agency about the conduct of the study at a particular investigational site;
- in response to sponsor concerns;
- upon termination of the clinical research site;
- during ongoing clinical trials to provide real-time assessment of the investigator’s conduct of the trial and protection of human subjects;
- at the request of an FDA review division; and
- related to certain classes of investigational products that FDA has identified as products of special interest in its current work plan (i.e., targeted inspections based on current public health concerns).
News headlines that attract the most attention tend to reflect serious allegations of fraud or negligence. The tendency may be to breathe a sigh of relief that such egregious offenses could “not happen here.” However, it’s the smaller, less obvious infraction that can slip through the cracks and cause serious headaches for investigators and their staffs. For example, if an inspector finds an issue with one clinical trial, the investigation may extend to your other trials.
FDA audits are usually just a routine procedure, but they can elevate the stress in a research office. Audits, whether in person or virtual, can last days, and questions are likely to come up.
As part of BRANY’s service to clients, a member from our quality team can work with research coordinators and investigators to organize documents for an efficient and orderly FDA review. There is much that the research site can do, however, to ease the process.
A review of research site audits we have conducted over the last several years highlights a few areas in which research staff can protect themselves before and during a trial.
Here are a few tips for being audit-ready at any moment.
Start with solid documentation. Starting on a strong foundation of detailed documentation will prepare your team for an inspection. Even if there are issues that come up during a trial, accurate and up to date documentation will outline how those issues occurred and were managed.
Organize each study topic. One of the most time-consuming efforts for research staff is organizing and properly labeling the materials. But this is an essential step in making information easily referenced and accessible.
We do not recommend relying on your electronic medical record to stand on its own. Because there are so many applications used by different institutions, regulators and auditors are not likely to want to navigate the software to find the information. The impetus is on the research office to extract and organize the information.
Refresh your memory. If the FDA does request an audit, take time review all the cases and review any issues that may have come up during the life of the trial. This will reduce your anxiety and risk of fumbling for answers should you be questioned.
Track any deviation from the protocol. Even if a sponsor approves a deviation from the study protocol, you are still required to log and report it to the IRB. Some changes can seem inconsequential. For example, a patient reschedules an appointment, so the follow-up occurs outside the defined timeframe. It must be documented and submitted. No deviation is too small for documentation and submission to the IRB. Remember to review monitoring reports for cited deviations and report to the IRB as required.
Additionally, it can also be beneficial to use a log to track concomitant medications, and adverse events.
Update credential and license information. For long-term studies, it’s important to review and update CVs and licenses in the regulatory binder. Review investigators’ medical licenses and update the documentation if they have expired.
Likewise, if your organization is using its own labs for processing specimens, it is important to update any CLIA or other certification documentation. Typically, lab certifications expire annually.
If you are packing and transporting any infectious agents, such as lab specimens, your personnel must receive training. The International Air Transport Association (IATA) has training for compliance in dangerous goods transportation. Anyone who collects, packs or ships these materials should be trained and certified; this must be documented in the regulatory binder.
Monitor your Delegation of Authority Log. If you add a new investigator to the trial, or hire a new research coordinator or study nurse, you must document the addition of any key personnel in your Delegation of Authority Log and have tasks appropriately delegated. This information must also be submitted to the IRB and confirm the key study personnel are IRB approved prior to performing key study procedures.
Conduct periodic internal reviews. With busy schedules, it can be tempting to wait for monitors to flag concerns. But it’s important to be proactive. Conducting a spot check every six months and a more detailed annual audit may protect you from panicked scrambling in the days before an announced FDA visit.
Being prepared for an audit does not mean hours of review. The secret of success is to keep regulatory binders up to date including sponsor correspondence, and IRB approval letters and correspondences, and to report changes and updates to the research to the IRB in a timely manner. If you doggedly track the seemingly small items throughout the course of a study, you will be in a good position to succeed in an FDA review.
Fair Market Value
One of the most critical first steps in preparing to launch a clinical trial is the development of a budget that covers expenses and compensates the research site. The budgeting process can be complex and requires detailed review of the protocol and a methodical line-by-line attention to detail. A properly negotiated budget ensures that a research site is reimbursed for all direct costs for conducting the study, as well as indirect administrative and overhead costs.
The challenge is in determining what is a “fair market value” (FMV) for those services. The U.S. Department of Health and Human Services’ Office of Inspector General (OIG) Guidance for Pharmaceutical Manufacturers provided initial guidelines for fair market value in 2003. The guidance stated that compensation must be “fair market value for legitimate, reasonable, and necessary services.” Since then, a variety of other federal regulatory agencies have also developed rules and laws regarding the compensation of investigators, clinicians, and medical facilities. While compliance with these standards is a mandate, the process of defining FMV may still be opaque.
Institutions at a Disadvantage
In determining the budget, research analysts or those developing the budget often rely on charge masters from each clinical department to set fees for services delivered during a clinical trial. On the other hand, sponsors use algorithms and databases to define so-called “fair market value.” The sponsors’ approach can put some institutions at an unfair disadvantage if the fair market value is determined to be below what the institution typically charges for the service.
The potential for dissonance between the two approaches can impact both large academic institutions and smaller research sites. Fair market value for one institution may not represent fair market value for another. For example, if an institution charges $2,000 for a procedure and another one charges $1,000, a sponsor may average them to $1,500. The institution that charges the higher fee may receive less than their estimated research budget on that service or procedure. On the other hand, a research site might not have access to a charge master or well-established methodologies for establishing their own fair market value and, therefore, have less insight to the real cost of conducting those services. The sponsor’s fair market value determination may well be below what the institution needs to cover its own costs, therefore they may operate the clinical trial at a financial loss.
Beyond the Budget: Ensuring Compliance
An accurate fair market value assessment also requires familiarity with federal regulatory guidelines and laws. Several regulations from a variety of agencies can influence how a research site sets a fair market value. They include:
- US Sunshine Act
- False Claims Act
- Stark Law for anti-kickback statutes
The Centers for Medicare & Medicaid Services (CMS) recently clarified key valuation terms for physician services. This may have implications for how physician-investigators approach their budgeting process. In addition to services, budgets need to account for administrative costs.
The CMS defines FMV as: “The value in arm’s‐length transactions, consistent with the general market value.” The final rule, published earlier this year, defines general market value as “compensation that would be paid at the time the parties enter into the service agreement as a result of bona fide bargaining between well-informed parties that are not otherwise in a position to generate business for each other.”
Creating Defensible Methodologies
There are several approaches to valuating compensation: based on projected income, costs, or the overall market. Each requires a careful analysis, and some approaches may not be appropriate for determining a clinical trial budget.
When evaluating budget line items, research professionals often gauge fair market value against the prevailing market rates. That means the budget reflects the analysis of recent similar transactions and may be based on industry or specialty percentile rankings. This can be problematic if the assessment is not done correctly. For example, the analyst should have a large enough sample size of comparable services against which to benchmark a cost.
Institutions should develop and adhere to a consistent and transparent methodology for evaluating fair market value. To help ensure adherence to federal guidelines, mitigate risks of non-compliance, and shore up a defensible FMV, we advise documenting the sources of information used in developing the budget. For example, what kind of database or charge masters do you use for assessing market rates for services? If you are estimating the time it takes to do a task, such as conducting an informed consent, be sure to have staff track and document their hours over a period of time so you can use this data collected to substantiate the rate utilized.
Of course, comparing your institution’s FMV against a community or regional benchmark is difficult, if not impossible, for individual research sites. At BRANY because we have worked with a multitude research sites, we are able to benchmark rates across regions and types of institutions. This positions research sites for better leverage in budget negotiations with sponsors.
Budgeting for a clinical trial is essential in ensuring fair compensation for the value of services offered by a research site. However, the field is complex and there is a large margin for error that can put the institution at risk of non-compliance. It is important for institutions to leverage the expertise of analysts with a comprehensive understanding of new guidelines, as well as standards that will ensure fair compensation and adherence to federal rules.
Proposed Cures 2.0 Act May Have Implications for Researchers
Members of the U.S. House of Representatives have introduced updates to the 21st Century Cures Act, which was signed into law in December 2016. The proposed legislation coincides with a detailed concept paper the White House published Tuesday in Science Magazine outlining their vision for the new research agency.
The 21st Century Cures Act, known as “Cures”, was initiated to modernize the U.S. healthcare system. The far-reaching law included provisions to advance precision medicine, accelerate the development of new medical products, and bring new innovations to patients more efficiently.
The new bill, called the Cures 2.0 Act would create an Advanced Research Projects Agency for Health, or ARPA-H, and would authorize more than $6.5 billion to run the agency. The mission of ARPA-H will be to speed transformational innovation in health research and speed application and implementation of health breakthroughs.
Under the terms of the lawmakers’ proposal, the new ARPA-H would be largely modeled after the military’s Defense Advanced Research Projects Agency, or DARPA, which has been responsible for successfully developing some of the most significant technological advancements of our time, including the Internet, GPS and self-driving cars. DARPA initially funded mRNA vaccine technology, which led to the development of a highly effective COVID-19 vaccine in record time that’s helped slow the spread of the virus both in the U.S. and abroad.
While the 21st Century Cures Act sought to improve how new drugs and treatments are researched and developed in the U.S., Cures 2.0 seeks to improve how those new treatments and therapies are delivered to patients.
The bill provides $25 billion to independent research institutions, public laboratories and universities throughout the country to continue their work on thousands of federally-backed projects. In addition to the funding, some of the sections of the legislation will have direct implications for researchers, specifically:
- Increase diversity in clinical trials.
- Require FDA to expand the collection and use of “real world evidence” to aid in the development of new, patient-focused treatment approaches.
- Require study sponsors to collect patient experience data in clinical trials.
- Ensure coverage for clinical trials under existing standard of care: allows Medicare to cover the costs of their beneficiaries in PCORI-funded clinical trials
- Increase access to telehealth services for patients covered under Medicare, Medicaid or the Children’s Health Insurance Program (CHIP) — possibly opening opportunities for more remote clinical trials.
- Provide grants for innovative clinical trial design and patient experience data to further build the science in these areas.
- Minimize or remove requirements for IND applications to initiate accelerated approval if sponsors meet proper criteria.
- Allow for use of evidence such as clinical evidence, patient registries, or other real-world evidence, to fulfill post approval study requirements to confirm the predicted clinical benefit of a therapy.
Reps. Diana DeGette (D-Colo.) and Fred Upton (R-Mich.) plan to hold roundtables about their proposal in June and July with the aim of releasing a final bill after Congress returns from its August break, according to reports.
ARPA-H Fact Sheet (https://upton.house.gov/uploadedfiles/final_cures_2.0_2-pager.pdf)
A section-by-section summary of the bill https://degette.house.gov/sites/degette.house.gov/files/Cures%202.0_DD%20SxS_FINAL1.pdf
Article published in Science (https://science.sciencemag.org/content/early/2021/06/22/science.abj8547)
Restarting Research Projects and Programs
The COVID-19 pandemic had significant impacts on clinical trials and research programs. According to researchers at Penn State, over 80 percent of clinical trials were suspended between March 1 and April 26, 2020, mostly due to the pandemic. The impact was more substantial for government or academic-funded studies than for sponsored trials, according to their study, which was published in March 2021. Among other concerns, researchers cited the challenges associated with recruiting and following up with patients.
Research leaders assembled task forces and started planning for the re-start of clinical and lab research as early as last summer. With unpredictable surges in cases in different states, the restart of research has not been uniform. This has required a high degree of flexibility among leaders and staff.
As vaccination programs roll out across the country, medical center campuses are updating their return-to-campus policies to accommodate the shifting landscapes. Physical distancing, use of masks and encouraging staff to continue remote meetings are still part of many campus policies. Each institution has to assess risk based on local risk factors and patient populations. Research professionals must constantly revisit processes and procedures for starting or continuing clinical trials programs, as well.
For industry sponsored studies, many trials shifted to remote monitoring and implemented telemedicine visits to minimize exposure to the coronavirus. Most institutions prohibited sponsor representatives from conducting in person site initiation visits and clinical trial monitoring. These restrictions are also beginning to be lifted.
Evaluate and Re-Allocate Resources
Campus closures were disruptive for staff as they often shifted their focus to supporting COVID activities on medical campuses. Some staff may return, others not. Turnover among clinical research coordinators was already high before the pandemic, and uncertainty about the future may have exacerbated this.
Recruiting and training new clinical research coordinators can be time-consuming and challenging under current circumstances. Research teams may need flexible staffing, or to ramp up activities quickly with limited staff. In these cases, it may be prudent to consider outsourcing much of the administrative and compliance work associated with clinical research.
Managing the many aspects of the COVID-19 pandemic this past year has also depleted financial resources at many institutions. Institutions have implemented hiring freezes because funding is scarce. Budgets for 2021/2022 are being cut all around including areas such as research administration.
Another question to consider: as restrictions are lifted to allow more clinical trials to begin again, and to open organizations for in person monitoring and site initiation visits will staff be available to support these initiatives?
Review Protocols for Deviations and Violations
It is important to understand the difference between a protocol deviation versus a violation, as there are implications for reporting requirements and IRB review.
Generally speaking, a protocol deviation occurs when, without significant consequences, the activities on a study diverge from the Institutional Review Board-approved protocol. For example, a patient may have missied a visit window because s/he is traveling.
A protocol violation is more serious. It refers to a divergence from the protocol that materially:
- reduces the quality or completeness of the data
- makes the Informed Consent Form inaccurate, or
- impacts a subject’s safety, rights, or welfare
If there are changes to the protocol, then IRBs may need to review updated patient consent forms. Additionally, some institutions are implementing e-consents and other technologies.
Communication with participates goes beyond consents. As return-to-campus protocols are modified, staff must advise research participants of any changes. For example, if a study moved to telehealth visits, and is now re-opening to in person visits, participants should receive the campus COVID guidelines prior to their next visit. Coordinators may need to communicate with participants regarding options that were implemented in response to COVID-19, and whether they will still be options as in person visits resume.
Identify Potential Budget Implications
Changes in protocols, methods of obtaining consents or conducting follow-up visits are just three ways in which a study budget can be impacted. Every change or accommodation to updated policies and procedures should be checked against the budget to ensure accuracy and appropriate reimbursement.
Experts are still debating what the future of work — and therefore, the future of clinical research — may look like post-pandemic. Regardless of the short- and long-term implications, it is essential for research staff to remain diligent and flexible in overseeing and updating procedures and policies.
Guide to Remote Audits
The United States reached the one-year anniversary of the first confirmed case of COVID-19, on January 15. Even now, as the rollout of vaccinations is underway, institutions are still facing campus and facility closures. We cannot underestimate the impact of COVID-19 on clinical trials and the research community. Institutions have had to refocus resources toward pandemic-related clinical care and research, which has caused delays, disruptions and cancelations of research in other clinical areas. Research coordinators and support staff continue to work remotely or in hybrid work situations.
Despite this, research professionals have demonstrated remarkable resilience and flexibility in adjusting to the new landscape. Over the last year, institutions have leveraged technologies to continue or start up clinical trials. Telemedicine has increased opportunities for remote consent and virtual study visits.
Restrictions on travel, in-person visits and access to research offices forced federal regulators to scale back their in-person surveillance activities, while increasing their remote audits to gauge compliance with Good Clinical Practices (GCP), Good Manufacturing Practices (GMP), and human subject protection (HSP). Investigators must be prepared for announced or unannounced inspections, particularly remote reviews.
A variety of situations can trigger an FDA inspection, from a serious adverse event (SAE) to reported violations of protocols. Just as your research team should be well prepared for in-person inspections, so should you be prepared for a remote visit. These are some of the areas where your team can prepare. In some instances, your team should coordinate with the IT department to ensure a secure, yet easily accessible, repository of information.
Gather and centralize stakeholder contact information
The names and contact information (mobile phones, pagers and email) of all key staff should be in a central place, such as a spreadsheet. This record can include:
- principal investigator (your materials should include the PI’s CV)
- clinical research coordinators
- laboratory technicians
You should also include any staff who should be notified in case of an audit, including contacts in:
- medical records
- risk management
Your contact list should include your primary contact at the study sponsor and/or CRO.
Digitize study documents
Depending on the requirements of your institution or the study sponsor, you may want to consider scanning regulatory documents and keeping them in a secure cloud-based file system. Consider including these items:
- IRB documentation, including the approval letter and amendments
- consent form (at least the latest version)
- study reference manual
- study protocol(s)
- sponsor instruction manuals
- policies and procedures
- roles and responsibilities for each of the key team members
- correspondence with the sponsor
- certifications (for example, for the laboratory)
- other essential documents as per Good Clinical Practice (GCP)
You should be prepared to upload participant documents such as signed Informed Consent Forms, Case Report Forms, and source documents to a file sharing application, following institutional requirements of redacting protected health information, if applicable. You may want to explore with IT granting auditors remote read-only access to the Electronic Medical Record for the participants selected for the remote audit.
Prepare a plan with stakeholders
The nature of remote audits may require more time to prepare requested documentation. It is important to prepare a plan and to educate your internal stakeholders on the procedures and areas of responsibilities in the event of an audit. A mock audit can test everyone’s response and identify risks and gaps. Don’t forget to include the IT department and staff in other departments who may need to play a role.
In the case of paper documents that are not scanned and uploaded in advance, you should have a plan for doing so upon request of the auditors. Identify a secure and HIPAA compliant storage platform and the mechanism by which you can obtain and upload those documents remotely that adheres to the institutional policy.
Be prepared to deliver a virtual “live” walk-through of facilities. Identify who will provide the tour and the technology necessary to do. Ensuring strong Internet connectivity in those areas, such as basement laboratories and other potential weak Wi-Fi zones can ensure a smoother experience for everyone.
It’s likely that remote work and, therefore, remote research surveillance will be part of the workflow for some time. Preparing for a remote audit can decrease stress and ensure clear communication among all the stakeholders.
The Importance of Real-time Data and Safety Monitoring
Researchers at Baylor College of Medicine Houston announced this week that they were stopping a clinical trial investigating the efficacy of convalescent plasma therapy in the treatment of patients with COVID-19. The reason, according to the principal investigator, was that statisticians had deemed the NIH-funded study to be futile. In other words, even with more patients enrolled in the study, the experts monitoring the data did not believe there was a realistic chance that convalescent plasma therapy would demonstrate efficacy.
Behind the headline is another important consideration: the importance for Institutional Review Boards (IRBs) to ensure that studies they approve have strong data and safety monitoring plans (DSMP). Data and safety monitoring functions are distinct from the requirement for study review and approval by an Institutional Review Board (IRB).
“Since IRB review occurs only at certain intervals, real-time data monitoring is typically done by a formal Data Safety Monitoring Board (DSMB) or another similar independent committee, as designated by the DSMP,” according to Linda Reuter, BRANY’s IRB Director. “As such, it is crucial for IRBs to consider the IRB approval criteria that risks to subjects are minimized and the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects by confirming that there is a plan to analyze the data at the appropriate intervals.”
“The IRB must determine that the provisions for data and safety monitoring are appropriate in order to approve a protocol,” adds Raffaella Hart, BRANY’s Sr Vice President for IRB and IBC Services. “Clinical trials should have a provision for data and safety monitoring that corresponds to the risks of the study.” The NIH has guidance on determining which studies require a Data and Safety Monitoring Board (DSMB). Multi-site clinical trials involving interventions that entail potential risk to the participants require DSMBs.
Review by an independent monitoring committee is especially important for multicenter clinical trials, as data from one site may not be enough to notice a safety signal at an early stage, but when data from multiple sites are aggregated and analyzed by the safety committee certain safety signals may become evident.
The method and degree of monitoring varies from one clinical trial to another and is based on the degree of risk involved, as well as the size and complexity of the trial. While not all clinical trials require a data and safety monitoring board, the NIH does set minimum standards for monitoring, including ensuring that monitoring is timely and effective and that those responsible for monitoring have the appropriate expertise to accomplish its mission. Monitoring plans typically include the following:
- Safety reporting requirements and procedures
- Rules for when to conduct interim analyses to assess safety and/or efficacy
- How the study will comply with any applicable regulatory requirements
- How the study will monitor site performance, including patient recruitment
- How to protect data integrity and participant confidentiality
- Statistical analysis procedures
Data and Safety Monitoring Board determines the safe and effective conduct of the trial, and establishes rules for deciding when it may be time to conclude the trial. The committee makes this important decision based on evaluating if significant benefits or risks have developed or the trial is unlikely to be concluded successfully. This was the case in the above-mentioned plasma therapy trial. DSMBs should include clinical trial experts, biostatisticians, bioethicists, and clinicians knowledgeable about the disease and treatment under study. Ideally, members should not have a vested interest in the outcome of the study, in order to avoid conflicts of interest.
“Early and ongoing data analysis is critical to the safety and protection of study participants,” says Ms. Reuter.
Is Your Institution Prepared to Identify Exempt Research?
The disruption of clinical research as a result of COVID-19 cannot be overstated. Virtually everything about developing protocols and starting clinical trials has been upturned. In some cases, trials have been closed indefinitely. Others have been delayed or streamlined. Much of the interaction, such as IRB review meetings, has been shifted online, decentralized or outsourced to free up resources in the fight against the pandemic.
Anecdotally, we have observed a change in the types of protocols submitted for IRB review, as many investigator-initiated trials have pivoted toward better understanding of COVID-19. At BRANY, we have seen an influx of exempt research — protocols that pose minimal risk and fit into pre-specified categories that are exempt from IRB review. This type of research still requires a determination that it meets criteria for exemption. The regulations do not specify who at an institution may determine that research is exempt under 45 CFR 46.101(b). However, the U.S. Office for Human Research Protection (OHRP) recommends that, because of the potential for conflict of interest, investigators not be given the authority to make an independent determination that human subjects research is exempt. The IRB is often tasked with making exempt determinations.
Institutions should develop standards and procedures for determining research is exempt. However, this can be complex and complicated as exempt categories must be interpreted for specific situations. In developing these policies, OHRP recommends the following:
• Develop standardized mechanisms for collecting sufficient information to make the determination. This can include checklists, standard operating procedures and requirements for training.
• Policies should clearly define who has authority to make these determinations and provide sufficient training for those people.
• Define categories for exemption and use them in making the determination. This is useful in case of audit, but also helps the institution to establish policies.
• Provide clear guidance to investigators about federal and institutional guidelines.
This last point is crucial, as there is no federal mandate that anyone other than investigator make the determination that a research study is exempt. Some institutions may be tempted to expedite research and avoid delays by allowing investigators to make these determinations. The provision of detailed checklists, or the use of a guided protocol writing tool such as ProtocolBuilder, may help the investigator in these cases. The OHRP, and we at BRANY, strongly advise that someone other than the investigator make this determination in order to avoid possible conflict of interest.
Research institutions and academic medical centers must continue to adjust to the rapidly shifting landscape brought on by COVID-19. Resources have focused on understanding the pandemic and have been funneled toward both interventional and observational research in this area. This has resulted in a possible increase in investigator-initiated studies that may be considered exempt. Institutions may need to review their policies and procedures for making these determinations to ensure they are both in compliance and, more importantly, continue to protect human subjects.
Trends: What We Are Watching in 2021
We know we are not alone when we say we are happy to put 2020 behind us. It was a challenging year for everyone, and we look forward to better days ahead. Despite the difficulties that the research community faced, we witnessed remarkable flexibility, resilience and creativity in dealing with significant hurdles. Last year lent new meaning to the phrase “hindsight is 2020.” In this article, we look ahead at 2021 and share the issues that we will be monitoring.
Diversity and inclusion in clinical trials
The COVID-19 pandemic highlighted serious racial and economic disparities in health care. Some racial and ethnic minority groups have been disproportionately affected by COVID-19. Conditions in the places where people live, learn, work, play, and worship affect a wide range of health risks and outcomes, such as COVID-19 infection, severe illness, and death. Long-standing inequities in social determinants of health that affect these groups, such as poverty and healthcare access, are interrelated and influence a wide range of health and quality-of-life risks and outcomes.
Likewise, racial and ethnic minorities are underrepresented in clinical trials. The research community, which includes industry sponsors and government agencies, is actively pursuing strategies that address disparities in clinical research. The FDA issued guidance in November aimed at enhancing diversity and encouraging inclusivity in medical research, specifically in the development of medical products. The industry trade group PhRMA adopted Principle 6, Commitment to Enhancing Diversity in Clinical Trial Participation, aimed at enhancing racial and ethnic diversity among clinical trial participants, with an effective date of April 14, 2021.
We will be watching how industry-sponsored and investigator-initiated trials implement strategies for increased inclusion.
Re-starting Clinical Trials
The pandemic led to the halting of hundreds of clinical trials. Lockdowns and other mandatory public health orders forced research staff to work from home and made in-person patient visits nearly impossible. Additionally, staff resources were redeployed to shore up shortages and support hospitals’ responses to the surge in COVID-19 cases in communities in the U.S. and around the world.
For some patients, particularly with end stage disease, the suspension of clinical trials had serious implications. Likewise, enrollment for new trials staggered as patients were wary of visiting any medical facilities. In an editorial in JAMA, researchers said “Mitigation efforts [against COVID-19] interfere with all aspects of a successful clinical trial: efficient accrual and randomization, intervention adherence and delivery, and outcome collection.”
Even now, research institutions are grappling with solutions to reduce the impact of fluctuating and shifting public health mandates on existing trials. Investigators continue to evaluate how to re-start trials safely.
Increase in Observational Trials
Investigators have immense opportunities to design and implement investigational trials evaluating patient outcomes and long-term effects of COVID, as well as different treatment modalities. Additionally, researchers may consider trials evaluating various aspects of the different COVID vaccines currently on the market as well as other that are in the development and approval pipeline.
Opportunities for social-behavioral-education research
Stay-at-home orders and increased isolation, negative impacts on the economy and lost jobs, not to mention a daily barrage of dramatic news and social media coverage, have led to an increase in stress and anxiety. The pandemic also led to a disruption in mental health services.
We are still learning what the long term social and behavioral impacts will be. But we expect to see an increase in studies to evaluate this.
Remote Monitoring and Decentralized Clinical Trials
Since the pandemic began, over half of all active clinical trials are using remote and virtual support, according to a study by The Tufts Center for the Study of Drug Development. We expect to see the continued use of telemedicine, remote monitoring and virtual IRB meetings and reviews.
Research professionals will continue to make adjustments to how they run research programs. Many institutions may need to make policy decisions in the absence of specific regulatory guidance.
In September 2018, the Clinical Trials Transformation Initiative https://www.ctti-clinicaltrials.org/projects/decentralized-clinical-trials defined decentralized clinical trials (DCTs) as those executed through telemedicine and mobile/local healthcare providers (HCPs), using procedures that vary from the traditional clinical trial model. For example, the investigational medical product is shipped directly to the trial participant).
The research community may need to continue to develop awareness and understanding about DCTs and/or hybrid trial designs, and what is in the best interest of patient safety as well as research integrity.
Using Digital Technology and Telemedicine in Clinical Trials
The trend toward digital technology, such as health tracking devices and virtual clinic visits, had started before COVID. The pandemic accelerated the implementation of these technologies to allow study participants to sign consents, submit vital statistics and data, and communicate with clinical research coordinators and investigators — all from the convenience of their home.
We are loath to make any predictions in this most unpredictable time. The story of COVID and its impact on research is still unfolding. With that, we plan to continue monitoring these issues and offering support to clients that are navigating these uncharted circumstances.
Happy new year from the team at BRANY.
Increasing Diversity in Clinical Trials
The FDA issued guidance in November aimed at enhancing diversity and encouraging inclusivity in medical research, specifically in the development of medical products. FDA Commissioner Stephan M. Hahn, M.D., wrote that “in order to promote public health, it is important that people who are in clinical trials represent the populations likely to use the potential medical product.”
Last week, the industry trade group PhRMA issued voluntary guidelines to members aimed at enhancing racial and ethnic diversity among clinical trial participants. Those guidelines go into effect in April 2021.
The FDA guidance discusses:
- broadening eligibility criteria and avoiding unnecessary exclusions for clinical trials;
- developing eligibility criteria and improving trial recruitment so that the participants enrolled in trials will better reflect the population most likely to use the drug, if the drug is approved, while maintaining safety and effectiveness standards; and
- applying the recommendations for broadening eligibility criteria to clinical trials of drugs intended to treat rare diseases or conditions.
The final FDA guidance addresses demographic diversity as well as non-demographic diversity, including people with co-morbidities, disabilities and wider weight ranges. Broadening inclusion eligibility for clinical trials impacts protocol design and methodological approaches.
The PhRMA guidelines specifically focus on outreach to communities of color to reduce health disparities. Activities include outreach and education, as well as the reduction of barriers to participation.
Exclusion and eligibility criteria necessarily balances risk of adverse events against the potential benefit of the research. Pregnant women, people with chronic or severe kidney disease, or complex medical conditions are often excluded from clinical trials due to risk. However, the FDA cautions against excluding certain populations out of habit or template, rather than based on strong clinical or scientific justification. Both sets of guidelines encourage broadening eligibility criteria to increase diversity when scientifically and clinically appropriate.
The FDA guidance addresses the logistics of participation and offers strategies for minimizing the burden on enrollees. For example, certain populations may find it difficult to visit research sites frequently. Researchers and sponsors are encouraged to consider alternative methods of engaging with participants, including phone or virtual visits, email, social media and digital devices.
Investigators and sponsors are encouraged to adopt enrollment and retention practices that enhance inclusiveness. Engaging patient advocacy groups in the design of protocols; increasing outreach and education through community organizations; expanding research sites to ethnic or underserved neighborhoods; hosting frequent recruitment events; and developing recruitment materials in multiple languages are just some of the suggestions.
While both the FDA and PhRMA address sponsored clinical trials, it can also influence investigator-initiated trials.
Broadening eligibility criteria and adopting more-inclusive enrollment practices should improve the quality of studies by ensuring that the study population is more representative of the population that will use the medical product if it is approved.
Critical Considerations for Remote Clinical Trials
Even as research centers and academic institutions re-open after shutdowns due to COVID-19, many researchers are looking at ways to use remote technologies in their clinical trials. In South Carolina, for example, nicotine addiction researchers are examining how to enroll smokers in their studies. They are evaluating e-consents, online surveys and questionnaires, as well as smartphone-enabled devices.
Historically, patient enrollment in clinical research has been a significant challenge. According to research by the National Institutes of Health, 80 percent of clinical trials fail to reach their enrollment goals within the prescribed timelines. Some sites fail to recruit a single participant.
Social media is a promising way to recruit potential research subjects. With its current ubiquity, social media enables researchers to reach broad populations and target subjects based on personal information. They can also reach physicians and other clinical practitioners to inform them of new trials.
However, there are important risks to manage, including privacy and transparency. Researchers who join online patient communities — for example, those focused on a particular diagnosis — should be clear of their role.
Learn more about Social Media and Research Recruitment in this webinar: Citi Program course informed consent and clinical investigations a focus on the process
Obtaining informed consent via electronic methods involves more than just video conferencing technology. E-consents require an adjustment in processes, which can be an adjustment for research coordinators or others obtaining consent. Proper training on process is critical to ensure informed consent is obtained appropriately and the rights and welfare of human subjects are continually protected.
Implementing e-consent also requires assurance that the technology platforms are in compliance with FDA requirements for electronic signatures. Institutions must consider issues such as privacy and data security.
Learn more about remote informed consent: https://www.brany.com/telehealth-clinical-research-and-informed-consent/
Virtual Patient Visits and Wearables
Investigators who are writing protocols must consider opportunities for virtual patient visits that will minimize exposure to clinical environments such as hospitals and clinics. The use of telemedicine technologies has exploded in 2020, as clinicians worked to maintain continuity of care during lockdown.
One critical element to consider for virtual patient visits is to include them in the budget. Recent news reports about insurance coverage of telemedicine visits demonstrate some shifts in reimbursement.
COVID-19 presented many challenges to clinical researchers. But it also offered many opportunities to revolutionize how investigators think about writing protocols, and how patients can enroll and participate in them. The landscape continues to shift rapidly, and requires careful monitoring to ensure both compliance and patient protection.
Telehealth, Clinical Research and Informed Consent
By most any measure, one of the biggest impacts that COVID-19 has had on the practice of medicine is the shift toward more telemedicine visits. Although the practice of delivering health services over the phone or the Internet has been around for some time, it wasn’t until the pandemic forced communities to close that clinical practices started to explore the use of technologies to continue monitoring patients remotely.
The global health crisis has forced both health care providers and regulatory agencies to pivot toward digital health services. Clinical research is no exception. Many clinical research studies were put on hold in the early days and weeks of the pandemic in the United States. Researchers and their staff were deployed to support COVID-19 efforts. Regulatory agencies had to adapt guidelines for HIPAA and other issues for the new environment. Health insurers developed policies for telemedicine and reimbursement.
Although clinical research in COVID-19 still seems to dominate at research institutions, protocols not related to COVID-19 are starting to return. Studies that were paused are also being resumed, albeit slowly and cautiously. Each institution has to assess risk based on local risk factors and patient populations. For studies that are primarily computational, or do not require in-person interventions, telemedicine may continue to dominate.
For research professionals, one critical issue is the process for consenting, or re-consenting, patients. For studies that were paused, investigators may need to re-consent patients due to necessary changes in the protocol. Participants may have to confirm their willingness to continue their participation in a trial.
These and other issues require consideration of the process of obtaining consent. Research coordinators, while familiar with the protocols, may need to adapt to the method of consent and how they explain the studies to patients via these technologies. The 2018 regulatory changes to consent forms that require a concise summary may be helpful in helping to communicate with potential participants. The remote consenting process may require more dialogue with the patient to ensure understanding.
These new processes can be an adjustment for research coordinators or others obtaining consent. Proper training on process is critical to ensure informed consents are conducted appropriately and continue to protect human subjects.
CITI Program, a division of BRANY, is hosting a webinar on informed consent on September 30, 2020 at 2PM EST.
Lessons Learned (so far) in COVID-19
Even as communities start the process of evaluating re-opening, many experts believe that a new normal will be with us for a long time. Physical distancing, face masks and ubiquitous alcohol gel will be part of daily life. The risk of recurrence spikes also looms ahead and threatens a return to stricter “stay at home” orders. Health care and higher education institutions continue to evaluate risks and will likely continue to encourage employees, including IRB and research administration staff, to work from home in order to maintain physical distancing. Research office staff have made incredibly quick adjustments in real time as the pandemic made its way through the United States.
In assisting our partners and clients make rapid changes, we learned some lessons we believe will help research institutions be more resilient in the months and even years to come.
Prepare for the unexpected
Disaster planning and business continuity are required for organizations receiving National Institutes of Health (NIH) funding. But even non-NIH funded research institutions should have robust business continuity plans in place. The elements of a disaster plan include issues such as data security and protecting human subjects.
Many organizations scrambled to get their staff up and running from impromptu home offices. From installing and learning video conference platforms to having documentation securely available online, many research professionals quickly adapted to new ways of working and collaborating despite the learning curve.
Research institutions and investigators should consider building in these technologies as a part of their daily operations:
- Web-based collaborative protocol-writing tools
- Electronic Research Protocol Management Systems and Clinical Trial Management Systems
- Online training for research staff, particularly for operations and regulatory compliance
- Secure online meeting/video conferencing applications
- Secure cloud-based document storage for regulatory materials and other essential documents
Build in flexibility
Many research institutions pivoted their resources toward COVID-19 research efforts. This means that internal resources are unavailable for ongoing work or pending projects. Being able to shift that work to external resources, including IRBs, allows for flexibility to respond quickly as situations evolve.
External IRB partners should offer processes and procedures for running IRB meetings virtually in compliance with regulatory requirements. They should also hold frequent meetings, with the ability to hold ad-hoc meetings as needed.
Other functions can be outsourced to strategic partners, particularly when rapid turnarounds are required. These include the development and management of study budgets, coverage analysis, and clinical trial agreement support.
Select the right partners
The historic scope of impact on the research community at every level demonstrates weaknesses in every system, including partnerships. As with any disaster, communication is often the first thing to fail. Tightly synchronized communication with responsive partners who act as an extension of the research team can be the difference between an inconvenience and a very costly mistake.
Research institutions have demonstrated great resilience in their response to COVID-19, and have continued to focus on human subject protection throughout their efforts. There is talk of a “new normal” in the aftermath of the pandemic. These lessons learned can help institutions retain the integrity of their research while remaining responsive to what may be a long-standing landscape in the months or years to come.
Chart Review Studies During and After a Pandemic
The current global pandemic combined with electronic medical records and data visualization technologies have resulted in unprecedented advances in real-time tracking of SARS-CoV-2, the virus that causes COVID-19, across countries, states and local communities. As the situation evolves, there will be ample opportunity and increased need for both retrospective and prospective COVID-19 research studies that involve the review of medical records.
The rapidly evolving situation in this global pandemic requires investigators to design and write protocols quickly for IRB review. A guided protocol-writing experience, as with ProtocolBuilder, streamlines the process, ensures regulatory and institutional compliance, and facilitates collaboration among researchers.
In medical record review studies, also called a “chart reviews,” a researcher may collect and analyze information that was originally collected for a different purpose, also referred to as a secondary use of data. It often involves the collection of data from medical records in order to evaluate possible relationships between different variables and specific outcomes measures. An investigator may assess biomedical, treatment or demographic variables by reviewing various elements of a medical record. These may include lab results, physician or summary notes, admission and discharge summaries, etc.
Chart review studies can also be designed to collect prospective data, meaning the patient data does not exist at the time the protocol is submitted to the IRB for initial review. While many chart review protocols may qualify for a determination of exempt status from the IRB or expedited IRB review due to the minimal risk to research subjects, these studies are still subject to IRB review and HIPAA privacy protections. A guided and structured protocol-writing experience can accelerate the process while enhancing compliance, supporting collaboration, and saving time.
A chart review study protocol will generally include the following key elements:
- A synopsis — includes the objectives and high-level summary of the study elements, including a study flow chart
- Introduction and background — includes the protocol statement of compliance
- Rationale — includes the problem statement, risks and benefits
- Literature review — a synthesis of the current literature to establish the relevance of the problem and description of the literature that supports the need for the study
- Research design and methods — includes the study population and duration of the study. For chart reviews, a date range that indicates the timeframe for which records will be queried (e.g., a review of all ER visits between 1/1/2020 and 7/1/2020)
- Data collection and handling — includes a plan for maintaining subject confidentiality and privacy, how data will be collected and stored
- Statistical analysis plan — how the data will be analyzed to achieve the objectives
Chart review protocols are emerging as an important methodology in understanding COVID-19. Given the rapidly-developing nature of the global pandemic, the need for prompt writing and review of these protocols is critical to the ongoing effort to understand the situation.
ProtocolBuilder, a cloud-based research protocol-writing tool, can help improve the quality and consistency of clinical research protocols to make internal and IRB review processes more efficient.
Research Study Design
Research and HIPAA Privacy Protections (part of Comprehensive CIP Course for Advanced Learners)
Preparing for COVID-19 Impacts on Research Institutions
The rapidly evolving federal, state and local policies regarding COVID-19 are impacting every walk of life in the United States and around the world. Companies, as well as academic and government researchers, have pivoted their focus on vaccines and possible treatments for the novel coronavirus.
Health and research institutions are trying to keep up with rapidly changing policies and procedures, while still providing patient care in real time. Resources at medical facilities are being activated and redirected to respond to the increase in testing and treating patients.
Research institutions and sponsors are evaluating protocols to determine which ones may be paused, altered, or continued. A phase three clinical trial investigating a diabetes drug has been put on hold in order to protect patients and workers, according to the sponsor. Some universities have issued “urgent ramp-down of on-site, in-person research activities” or are downright “suspending all non-critical on-campus research activities.” Investigators are encouraged to check with their institutions’ research offices and sponsors for the latest information regarding trials in which they are involved.
Institutions must address several critical issues as they develop their policies, but the most important is the health and safety of patients and staff. Institutional review boards, research offices, laboratories and environmental health and safety committees must work together to provide guidance to investigators and research teams. These are some of the considerations in developing a policy:
- Flexibility — The situation is changing rapidly, as are federal, state and local mandates regarding the mobility of the public. In communicating with staff, it is important that they recognize and acknowledge the fluidity of the situation, and that policies may be revised in response.
- Continuity plans — Policies should consider continuity or contingency plans to protect the integrity of ongoing research. In some cases, disaster plans can be consulted for guidance in this situation.
- Communication with patients — Investigators and research offices will need a plan for communicating with patients and human subjects. Some institutions are waiving IRB review of these urgent communications.
- Reporting study deviations — IRBs will likely require reporting of study deviations, or have modified policies for doing so. Check with your IRB.
- Remote work contingencies — With many non-critical staff working from home, policies should address the use of video conferencing for IRB and other meetings, remote access and security of HIPAA-protected data, and so on.
- Telemedicine — Researchers may want to consider the use of telemedicine technologies to conduct study visits.
The rapidly changing landscape, the urgency and scale of response, and the impact on health care institutions is making this an unprecedented situation for everyone. Protecting the physical and emotional health of workers and patients should be at the center of our attention as we navigate uncharted territory.
Below are some resources for investigators who are conducting NIH-funded research:
National Institutes of Health
Global Impact on Clinical Trials
Challenges and questions remain as the one year anniversary of the implementation of the Revised Common Rule approaches
One year has passed since the implementation of the Revised Common Rule, and many challenges and questions remain. While IRBs wait for promised guidance to materialize, we are left to interpret various aspects of the rule ourselves. This has resulted in variability across IRBs in how the new requirements are interpreted and operationalized.
Variability in the Key Information Summary
A significant area of confusion and variability relates to informed consent. The Revised Rule requires that “informed consent must begin with a concise and focused presentation of key information that is most likely to assist a prospective subject or legally authorized representative (LAR) in understanding the reasons why one might or might not want to participate in the research.”
Overall the response to the requirement for the Key Information section has been positive among IRB members since it provides an opportunity to highlight the most important information. However, significant challenges remain. IRBs have come up with a wide variety of approaches to meet this new requirement, ranging from brief paragraphs to lengthier, organized tables of information.
In our experience, industry sponsors have also not uniformly grasped the intent of this section, which is meant to be concise. Sponsor representatives often cut and paste long, complicated sections of risk language from the main body of the consent document (often multiple pages worth). This creates complex key information sections, resulting in more work for those who prepare consent documents, and more back and forth with sponsors.
Broad Consent Poses More Questions
Some additional informed consent issues that have been problematic relate to the provision of “clinically relevant research results” and under what circumstances they should be provided back to subjects, the statement regarding future use of research specimens, and the required element regarding whole genome sequencing.
Although the broad consent option was intended to give researchers better options for obtaining consent to use information and specimens for research, the fatal flaw seems to be the requirement to track refusals. Given the final rule’s definition of what was identifiable, and the removal of the concept that all biospecimens are identifiable, the need for a mechanism such as broad consent was diminished. As a result it seems that institutions are not utilizing the new broad consent option.
Institutions, particularly large medical centers with multiple facilities, still need guidance on how to operationalize the mechanism of broad consent. How far does the refusal to broad consent have to be tracked? What if an individual visited multiple facilities and gave conflicting answers to the request for broad consent? What if an individual changes their mind? Broad consent does not appear to be a great option for most research institutions at this point.
Navigating the Transition
For IRBs that have not transitioned studies that were approved prior to January 21, 2019 to the Revised Rule, another challenge is having two sets of rules to follow, as some studies fall under the pre-2018 requirements, and others under the 2018 requirements. An additional complicating factor is the lack of harmonization with FDA regulations. For many, their systems had to be customized to allow for labelling of studies so it is clear which regulations are applicable to a particular study. IRB reviewers also need to be particularly cognizant as they review multiple studies for one meeting, as there is no one set of rules to follow.
The transition to the revised Common Rule has been challenging to a community that worked under rules that remained largely unchanged for several decades. While the changes were definitely needed, and welcomed by most, there will be growing pains. As exemplified by some of the scenarios above, some areas will need to be refined as we gain experience in applying the new rules. While we patiently wait for guidance and harmonization, IRBs continue to do a magnificent job of sharing best practices among each other. At the end of the day IRBs seek to protect the rights and welfare of research participants, despite any hurdles that come along.
The Critical Issues You Need to Track During a Clinical Trial
Congratulations! You have gone through all the necessary steps to launch a clinical trial. Now it’s time to move on to the next one, right? Wrong! A successfully managed clinical trial requires ongoing tracking throughout its duration. Careful monitoring ensures your research institution remains compliant and that your site is compensated properly for the study.
Follow our series on the key critical issues you need to track throughout a clinical trial.
Part Two — Budgeting and Maximizing Revenue
Research sites that have a clear process for clinical trial budgeting as well as billing and collections can ensure their research efforts are feasible and sustainable.
An initial process that thoroughly accounts for every expense related to the clinical trial will result in a thoughtful budget that supports site resources. In addition to completing a Coverage Analysis to determine research procedures from standard of care procedures, research coordinators should consider costs that may be “hidden” or less obvious such as protocol specific training, or time needed for site initiation and monitoring visits. A detailed budgeting process up front will make tracking study activity and expenses much easier. Besides the expenses related to patient visits, budgets should include line items that cover time and effort of the investigator, the coordinator, and other research personnel for the various administrative tasks necessary to effectively carryout the requirements of the study. These administrative tasks can include:
- Screening for eligible participants
- Responding to sponsor queries
- Reviewing safety reports
- Preparation of regulatory documents or maintaining the regulatory binder
Throughout the study, it is important to track not only visits and procedures, but also items for which you need to invoice the study sponsor or CRO. Invoiceable fees can include procedures done outside the study visits, such additional scans, lab tests, or unscheduled visits. If patients are reimbursed for travel or other expenses, these should also be tracked.
To ensure research billing and collections are maximized it is essential to have strong systems in place to track all study visits and procedures completed throughout the study and record all the activity in comprehensive invoices. It is also important to track study payments and accounts receivables. Reconciling payments received from the sponsor/CRO to the study budget and to the actual study activities completed is critical. If you do not receive payment for all study activity your cash flow and profitability are impacted.
Careful tracking of all study activity, billable expenses, and sponsor/CRO payments help ensure that your site will have positive cash flow and cover its costs related to operating clinical trials.
The Critical Issues Sites Need to Track During a Clinical Trial
Congratulations! You have gone through all the necessary steps to launch a clinical trial. Now it’s time to move on to the next one, right? Wrong! A successfully managed clinical trial requires ongoing tracking throughout its duration. Careful tracking ensures your research organization remains compliant and that your site is compensated properly for the study.
Follow our series on the key critical issues you need to track throughout a clinical trial.
Part One — Protocol amendments
This is likely one of the most common and time-consuming of the issues that require tracking. A Tufts University study found that over half of sponsored studies have at least one significant amendment.
Protocol amendments are inevitable, and some trials undergo multiple amendments throughout their duration. But some revisions are so significant it could feel like starting all over again.
There are generally two kinds of protocol amendments — administrative updates and substantive protocol revisions. Administrative changes are typically minor, and may involve grammar, wordsmithing, punctuation or small editorial changes. Significant amendments are any changes that may impact the safety of participants, and can include any change to the design of the protocol, including:
- Change to the dosing or duration of participant exposure to a drug
- Change to the design of the protocol, such as the inclusion or exclusion criteria or the addition of treatment arms
- Addition of new tests or procedures
IRB review and approval is required in order to carry out the visits and procedures that are part of the amended protocol. IRBs often require the following information when submitting an amendment:
- A description of the differences between the original protocol and the amendment
- Revisions to the informed consent, if applicable
- Revisions to any marketing or patient recruitment materials
Protocol amendments can impact patient recruitment efforts. In fact, some protocol amendments may also affect a site’s ability to enroll if there are significant changes to inclusion or exclusion criteria. Often the consent form must also be revised to reflect the changes to the protocol. Patients may need to be re-consented with the updated, IRB approved version of the consent form so they can be made aware of changes in protocol procedures.
Depending on the scope of the protocol amendment, your research site should review the study budget, as the necessary procedures may have changed or new procedures and visits may have been added. In our experience, amendments have an impact in roughly half of all study budgets. A full review of the budget, and possibly a revised Medicare Coverage Analysis, may be necessary.
Create a checklist
The more you prepare and plan for protocol amendments, the smoother the process to implement the amended protocol. The use of a checklist or systematic approach will ensure that no steps are overlooked.
Whenever there is a protocol amendment, clinical research coordinators should make sure they update the following:
- IRB/IEC and other regulatory submissions
- Informed consent documents, including oral consent scripts
- Marketing, advertising or recruitment materials
- Sponsor contract, particularly if there is an impact to the budget, and coverage analysis, if applicable
Studies have shown that protocol amendments can impact the cost and duration of clinical trials. But with some careful preparation, clinical research coordinators can ensure a smooth administration of the changes.
News Release – BRANY Names Michael Belotto as Chairperson for Social-Behavioral IRB
BRANY (brany.com) has announced that Michael Belotto, PhD, MPH, CCRC, CCRA, will serve as chairperson for their social-behavioral IRB. The SBER IRB is comprised of a multidisciplinary group of experts in social and behavioral research, as well as human subject protection.
“Dr. Belotto has been a great contributor to BRANY IRB’s success over the past 20 years,” says Raffaella Hart, MS, CIP, Vice President, IRB and IBC Services for BRANY. “In serving as an IRB member and Quality Assurance auditor, he has been dedicated to ensuring that investigators conduct research in compliance with federal regulations and ethical guidelines. Researchers and research participants will be well-served with Michael serving as the Chairman of BRANY SBER IRB.”
BRANY started the SBER IRB in 2016 in response to an unmet need identified by social, behavioral, and education researchers. Common feedback from this group of researchers centered on the fact that most IRB processes and procedures were rooted in biomedical research which often did not align with the needs of social and behavioral researchers. The issues in social-behavioral research are distinct from biomedical research in a variety of critical ways, and need the review of experts in the relevant fields. Research protocols can include graduate student dissertations, research outside the U.S., as well as focus groups.
Dr. Belotto serves as a research compliance expert responsible for auditing sites to ensure investigators’ compliance with FDA regulations and ethical guidelines. He will continue to serve as a member of BRANY IRB in addition to chairing the SBER IRB.
Dr. Belotto worked as a paramedic in the New York City Emergency Medical Service 9-1-1 system for 10 years, with 7 years of experience in Hospital Administration.
Dr. Belotto is a graduate of New York Medical College where he completed a Master’s in Public Health with a concentration in epidemiology. He completed his doctorate in Public Health at Walden University.
The SBER IRB is part of BRANY’s Connected IRB model, which helps maintain an ongoing connection among investigators, institutions and the IRB, by promoting communication with key stakeholders. This includes email alerts for investigators and research coordinators as well as specific alerts for critical concerns such as unanticipated problems involving risks to subjects or others.
New CITI Program Courses and Webinar Help Researchers and Institutions Meet Regulatory Requirements
(Miami, FL) — The Collaborative Institutional Training Initiative (CITI Program), a division of BRANY, has announced new online courses and webinars designed to help research professionals understand and comply with regulatory requirements for clinical trials.
The three courses and webinars address critical regulatory requirements:
- Transitioning research to the Revised Common Rule
- Protocol registration and disclosure on ClinicalTrials.gov
- The role of principal investigators in meeting regulatory requirements
Transitioning Research to the Revised Common Rule: The What, How, and Why, a webinar that outlines considerations and challenges for transitioning pre-existing research to the revised Common Rule, as well as required documentation and tips for IRB review, is offered to both institutions and individual learners.
Designed for research professionals, including investigators, institutional review boards and research staff, the webinar reviews pre-2018 and 2018 versions of the Common Rule, including factors an organization may want to consider when deciding whether to transition a pre-existing study (or studies) to comply with the revised Common Rule, and strategies for the management and communication of transition decisions.
The webinar is presented by Karen Christianson, RN, BSN, a principal with HRP Consulting Group.
Recently published research demonstrates that many research institutions are not prepared to meet current requirements for registering and reporting clinical trials. A new course addresses this gap.
Protocol Registration and Results Summary Disclosure in ClinicalTrials.gov, an innovative video-enhanced course, guides learners through critical parts of the regulations and provides a step-by-step guide to data entry. This course can help organizations/investigators clearly understand protocol registration requirements to avoid the risk of significant civil monetary penalties or loss of NIH grant funding due to non-compliance with protocol registration and results reporting.
Biomedical PI focuses on key topics essential to the biomedical investigator’s role and responsibilities in conducting a clinical investigation of a product regulated by the U.S. Food and Drug Administration (FDA). This role-based course covers supervision, delegation, management, reports, and communication for investigators.
These courses, along with dozens of others available at CITIprogram.org, train investigators and research professionals to understand and meet research ethics standards and compliance requirements.
About CITI Program
The Collaborative Institutional Training Initiative (CITI Program), a division of BRANY, is dedicated to promoting the public’s trust in the research enterprise by providing high quality, peer-reviewed, web-based educational courses in research, ethics, regulatory oversight, responsible conduct of research, research administration, and other topics pertinent to the interests of member organizations and individual learners.
Four Essentials for Clinical Trial Enrollment
Clinical trial enrollment continues to be one of the most vexing challenges for research institutions and sponsors. Despite one quarter of sponsors’ clinical trial budgets being allocated to enrolling participants, half of research sites enroll only one or no patients in studies. Recruiting a diverse patient population is an even bigger challenge, with ethnic minorities, women and the elderly often underrepresented in clinical research.
Typically a contract between an investigator and the sponsor will outline the number of participants to be enrolled. The inability to enroll the required number of patients can have serious implications for the study’s success. Eighty percent of clinical trials fail to finish on time and 85 percent fail to retain enrollees, leading to canceled trials. Not meeting enrollment targets can dampen the relationship between the investigator and the sponsor and perhaps diminish future opportunities for the research site.
The vast majority of patients are willing to enroll, if only they know it’s an option. Eight-five percent of patients were either unaware or unsure that they could enroll in a trial, according to a Harris Interactive Survey of cancer patients. But 75 percent of these patients said they would have been willing to enroll had they known it was possible.
Sponsors are turning to artificial intelligence, machine learning and other technologies to provide detailed predictive analytics in an effort to improve recruitment. These technologies can comb through thousands of electronic medical records and other demographic data, and cross-reference criteria from hundreds of available trials. Microsoft just announced a chatbot designed to match patients to trials.
Sponsors must continue to work closely with research sites to coordinate the most effective methods of finding and enrolling patients, however. Even with new technologies, research coordinators and investigators play the most important roles in the successful recruitment and retention of clinical trial participants. By nurturing relationships in patient communities, a human-centered approach can yield demonstrably improved results.
Budget for recruitment. Recruitment and enrollment takes the time of the research coordinator and other staff—time that needs to be accounted for in the study budget if the research institution is to avoid working at a loss. When budgeting, consider the entire process of patient recruitment, not just the advertising budget, to ensure an accurate assessment of resources used.
Collaborate with colleagues. Investigators and research coordinators should network and collaborate with their colleagues in other specialties, and leverage these relationships to encourage patient referrals to clinical trials. Many clinical trials cross over different specialties. For example, a study may encompass both cardiology and endocrinology for heart disease and diabetes. Creating a network, even an informal one, to share ideas and proactively discuss clinical trials with their patients will raise awareness.
Understand the compliance issues. Compliance issues impact patient enrollment in a variety of ways. For example, if you will be reviewing medical records to identify potential research participants, you may need a partial HIPAA waiver for recruitment purposes from the IRB to share information.
Compliance also impacts any traditional advertising and marketing. Sponsors may sometimes run larger national awareness campaigns for certain clinical trials, but for others it’s often up to the investigators to reach out within their own community through traditional advertising methods. This can include newspapers, radio and local cable television. It can be as simple as distributing flyers in places where potential participants may see them. Whatever media you use, the IRB needs to review the material before it is released. Physician-to-physician letters may not require IRB review so check your IRB’s policies in advance. Consider advertising a step in your recruitment plan.
Monitor progress. In the course of running a busy clinical practice, it may be easy to let your recruitment efforts slip. At the beginning of the trial, schedule regular “touch base” meetings with your team to learn what you are doing to recruit participants and how successful those efforts are. If an activity is not yielding results, you can replace it with something else and not waste unnecessary time and effort.
Technologies are moving rapidly in artificial intelligence and machine learning. Staying abreast of these developments and trends can keep you ahead of the curve and aware of opportunities for your practice. However, personal relationships and human contacts are still an essential part of the patient recruitment toolkit.
 Clinical Leaders
Burnout Among Research Coordinators — Warning Signs and How to Avoid Them
Let’s face it. Every job has its challenges. However, burnout seems to be at an all-time epidemic level. A recent report from Harvard University highlighted physician burnout as a public health crisis. A keyword search for “preventing burnout” yields 15 million results in Google. In the United States, problems associated with burnout are estimated to cost more than $120 billion a year.
Burnout is typically defined as a response to prolonged stress. Key signs are emotional exhaustion, cynicism or detachment, and feeling ineffective. The results can include a feeling of isolation, irritability, and even frequent illness and absenteeism. One study indicates that up to eight percent of annual healthcare costs are associated with and may be attributable to how U.S. companies manage their work forces.
Research coordinators, too, face burnout that may be resulting in high turnover rates, low enrolling studies, disrupting workflows and even delaying the start of clinical trials. Certainly at many institutions, risk factors are in place for research coordinators to experience burnout — increased workloads, few opportunities to learn, lack of feedback and limited autonomy.
There are thousands of articles and blog posts about preventing burnout, often putting the impetus on the individual. Many articles cheerily extol professionals to “find life work balance,” eat a balanced diet, exercise or get some sleep. Preventing burnout is not the sole responsibility of the individual to self-manage. There is a vast database of scientific research on workplace predictors of employee burnout. The reality is that organizational culture is a primary driving cause of burnout.
Here are some steps your organization can implement to reduce the risk of burnout and increase motivation and engagement among research staff.
- Offer ongoing professional training. The field of clinical research is constantly shifting, with the regulatory landscape increasingly complex. Professional training increases competence, which improves performance.
- Look for opportunities to provide autonomy. With training, research coordinators can have the appropriate knowledge and confidence to manage some workplace decisions. This is especially the case in places with high workload and emotionally demanding clients, such as patients. And while research coordinators are often extremely independent in their work style, researchers must remain diligent in keeping lines of communication open and regularly meeting with their research team.
- Provide feedback. Researchers and clinicians are busy, also, dealing with their own job stresses. Despite this, clinical research coordinators and other research staff benefit from receiving constructive feedback, including explicitly expressed appreciation from senior leaders.
- Be realistic about workload. Every job has its times of increased demands. But if daily workload transforms into a chronic overload, there can be serious implications. Leveraging outsourced solutions can ease some of the pressure when overload situations arise. Partnering with outsourcing service providers that can work as an extension of your institution, can complement the internal staff responsibilities.
Given the negative impact of burnout on individuals’ well-being and workplace performance, it is critical that organizations seek proactive ways to create cultures that support and engage their staff.
The Revised Common Rule and Informed Consent: Public Posting
An important provision in the Revised Common Rule is the requirement to post, to a publicly-available federal Web site, a copy of an IRB-approved version of the consent form that was used for enrollment purposes for each clinical trial conducted or supported by a federal department or agency. The Office for Human Research Protections (OHRP) has identified two publicly available federal websites that will satisfy the consent form posting requirement in the revised Common Rule: http://ClinicalTrials.gov and a docket folder on http://Regulations.gov. It is possible that additional sites may be identified in the future.
The consent form will need to have an up-front concise and focused presentation of the key information as required by 46.116(a)(5).
The specific requirement is that an IRB-approved consent form that was used for enrollment purposes be posted. There is no requirement to post multiple forms for multicenter studies, or for a study that has separate consent forms for different subject groups (e.g., adults versus pediatric participants). Also, for consent forms that underwent revision over the course of the study, the final rule does not stipulate that the posted document be the most recently approved version.
The posting can take place any time after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject, as required by the protocol. Information that should not be made available on a federal website, as determined by the federal department or agency supporting or conducting the clinical trial, can be redacted.
The purpose of the new provision is to increase transparency, which some feel will lead to improved consent form quality. The commentary to the Final Rule, describes how having an easily accessible repository of such forms freely available for analysis and public discussion will foster public discussion and create multiple opportunities for improving these forms, and thereby improve one of the most important aspects of our human subjects protections system.
For More On The Revised Common Rule and Informed Consent, see our previous article on Consent Waivers
The Revised Common Rule and Informed Consent: Consent Waivers
The Revised Common Rule has a few important changes regarding consent waivers.
Under the revised Common Rule, broad consent is provided as an alternative to the informed consent requirements for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens. If an individual was asked and refused to provide broad consent, the IRB is prohibited from waiving informed consent at a later date for the use of the subject’s identifiable private information or identifiable biospecimens in a secondary study. This means that this information must be tracked. This may be complicated, particularly for larger health care institutions and systems, and therefore the broad consent mechanism may not be widely utilized.
Of note is that the use of the individual’s materials in a nonidentifiable manner in secondary research continues to be permissible, even if there was a refusal to broad consent, since this particular use would not otherwise require a waiver of informed consent since the activity does not constitute research with human subjects.
The Revised Common Rule also adds a new waiver criterion. In order to waiver or alter consent, the IRB must find and document the following:
- The research involves no more than minimal risk to subjects;
- The waiver or alteration will not adversely affect the rights and welfare of the subjects;
- The research could not practicably be carried out without the requested waiver or alteration;
- (New as of January 21, 2019) If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format; and
- Whenever appropriate, the subjects or legally authorized representative will be provided with additional pertinent information after participation
The term “practicably” has not been clarified in the revised rule.
In the case of recruitment and screening of research subjects, the pre-2018 rule required an IRB to determine that informed consent can be waived under the .116(d) criteria before investigators could record identifiable private information for the purpose of identifying and contacting prospective subjects for a research study. Although not considered a “waiver,” under the new rule, an IRB can approve an investigator’s proposal to obtain information directly from a prospective subject, or to obtain already collected identifiable information or identifiable biospecimens by accessing records or stored biospecimens, for purposes of screening, recruiting, or eligibility assessment, without the informed consent of the prospective subjects.
The Revised Common Rule’s section on waivers or alterations of consent can be complicated, so it is important for research professionals, researchers and IRBs to review the changes and the exceptions.
For More On The Revised Common Rule and Informed Consent, see our previous article on Broad Consent
Career Series: Early Career
How to Attract and Keep the Best Research Coordinators
This is part of a series on career development for research professionals.
One of the most challenging responsibilities for an investigator is the recruitment and retention of talented staff, particularly research coordinators. Nationwide, there is a high turnover rate among research coordinators. This disruption in staffing can lead to delays in conducting research, from missing deadlines to entire studies being stalled.
Investigators recruit research coordinators from a variety of sources. Sometimes the role of study coordinator is viewed as an entry-level position, and those individuals hired to fill the role can be new to the workforce, and may have little experience. Many may be so-called Millennials, recently out of college.
Millennials, generally speaking, were born between 1980 and 2000. They are considered one of the most educated generations of our times. Their numbers are huge, surpassing those of the baby boomers. Much has been studied and written about their attitudes toward work and career growth.
Millennials in the workplace can be dedicated and creative, and eager to make a significant contribution to your research site. To retain this young talent and minimize the risk of study disruption due to turnover consider the following tips:
Respect the balance between work and personal life.
Unlike Baby Boomers, younger workers tend to integrate their work and personal life in a more fluid way. They prefer not to have a distinct separation between the typical eight-hour work day and their personal interests. That said, they tend to be more protective of their personal time.
Practically speaking, this means they prefer more flexibility in their work day. They may be willing to work later in the day, or evenings, as long as they can take some time during the day to run errands or do other things.
Provide opportunities for learning and professional development.
Millennial workers are easily bored and need to feel they are growing and expanding their knowledge. Invest in their professional growth by offering access to online courses — either focused on research or on specific skills. This will keep them engaged.
Think beyond salary.
While millennial workers understand the important of earning an income, a high salary is not the primary driver for work place happiness. Beyond a salary, consider offering flexible work hours, additional days off, or opportunities for telecommuting.
Avoid isolating millennial workers.
The work of a research coordinator can be solitary, with them working independently from others in the office. It requires a fair amount of entrepreneurship and independence. However, Millennials are usually motivated by dynamic, cross-functional positions. They also seek jobs that allow them to be in contact with and learn from interesting people, interacting with other professionals and teams.
If your millennial research coordinator reports directly to you, it is important to honor your time together to discuss projects or studies. Ensure they can participate in office meetings so they can gain an appreciation for how their work might be connected to other activities in the office.
Provide a constant feedback loop.
For Baby Boomers, performance feedback had traditionally formal review process tied to promotion and compensations, conducted at specific times. For Millennials, feedback is informal and is expected throughout the work week.
Give them a sense of purpose.
Millennials are inspired by a vision or purpose, not by a list of tasks. Millennials, in general, will not be content to simply complete forms and file documents. They are looking for meaning in their work. Remind them of the importance of their work in human subject protection. Keep them in the loop about the value of clinical research at your research site — the impact on medical knowledge in general and on patients specifically.
Leverage their knowledge of social networks.
The world of Facebook, Twitter, Instagram and Snapchat is a daily part of their lives. They will not react well to feeling disconnected, even at work. In fact, research shows that over half of Millennials would turn down a job that denies them access to social networks.
Their adept use of social network sites can help gain insights that may help you improve your study participant recruitment, as well.
In general, they key driver for Millennial job satisfaction is a sense of connection and purpose. A lack of connectivity makes them feel isolated, and they are likely to move on to other opportunities. A fully engaged Millennial research coordinator can, however, be a dynamic part of your research team.
Gene Therapy Research — Is Your Institution Ready?
Recent news about approved immunotherapy and gene therapies has generated excitement around the possibilities of treating difficult diseases. Organizations have increased funding in this area, including a recently announced $1.3 million grant in funding by the Alliance for Cancer Gene Therapy for research in gliobastoma, sarcoma and ovarian cancer.
The increased attention and funding means that more research institutions may enter this exciting field of research. However, institutions may not be fully aware of the specific NIH guidelines and requirements for gene transfer research in addition to IRB review. An institution that receives NIH funding or conducts NIH funded recombinant DNA research is required to follow the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (“NIH Guidelines”). Even if the funding source is a private entity, it is still advised that institutions comply with the NIH Guidelines to ensure the safety of research teams and the communities they serve.
The NIH Guidelines define human gene transfer as the deliberate transfer into human research participants of either:
- Recombinant nucleic acid molecules
- DNA or RNA derived from recombinant nucleic acid molecules
- Synthetic nucleic acid molecules, or
- DNA or RNA derived from synthetic nucleic acid molecules that meet certain criteria
An institution that engages in gene transfer must establish an institutional biosafety committee (IBC). This committee can be administered either internally (by the institution), or by an experienced external group. The IBC must have at least five members, two of whom must not be affiliated with the institution. The role of the IBC is distinct from the role of an Institutional Review Board (IRB). The IRB’s focus is on protecting the rights and welfare of research participants, whereas the IBC assesses the containment levels, facilities, procedures, practices, and training and expertise of personnel involved in recombinant or synthetic nucleic acid molecule research.
Research involving recombinant or synthetic nucleic acid molecules requires IBC review because additional safety measures are needed. The risk assessment for these agents must be done by qualified experts experienced in biosafety guidelines, including physical and biological containment requirements. Those conducting this research need to understand and identify the biosafety level of the particular investigational agent — level one being the lowest level and level four being the highest. Each level has specific parameters that must be met with relation to precautions needed, such as containment levels, staff training requirements, and the experience required of those handling the agent.
Risk is assessed by evaluating the following:
- Staff training — are they trained in handling the agents according to guidelines and standard operating procedures?
- Protocol — does the protocol outline how the agents are handled, including waste precautions and decontamination procedures?
- Recordkeeping — how are records documented and kept?
- Procedures — how and where is the agent or drug constituted?
- Community safety — what mitigation steps are in place to protect the community?
While the prospect and promise of human gene transfer research is exciting, institutions and researchers must understand the requirements when working with these investigational agents.
When research involving recombinant DNA is NIH funded or conducted at a site that receives NIH funding, failure to comply with the NIH Guidelines could risk that funding or result in additional requirements by NIH for the conduct of such research. Leveraging an external team of experts fluent in biosafety, the NIH Guidelines, and IBC administration can provide an immediate framework for an institution to build upon that will ensure the safety of local research teams and the surrounding communities in an ethical and efficient way.
BRANY protocol launch showcases paradigm shift in behavioral and social sciences research
Please read the attached Centerwatch Article to learn how social, educational and behavioral research is distinct from biomedical research when it comes to writing study protocols. cww2131_BRANY