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.

Various studies had projected a shortage of healthcare workers even before COVID-19. But early studies suggest the pandemic may have accelerated the trend.

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.

Continuous learning

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.

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.

Further resources

Medicare Coverage Related to Investigational Device Exemption (IDE) Studies (CMS)
https://www.cms.gov/medicare/coverage/ide

 

 

When an Investigator is also a Sponsor

When investigators embark on designing, writing, and initiating the clinical trial, their responsibilities are just beginning. The FDA calls these investigators “sponsor-investigators (SIs)”. A sponsor-investigator is an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. In other words, in an investigator-initiated trial, the researcher is both the investigator and the sponsor, and therefore must handle the responsibilities for both roles.

The FDA provides guidance for individual investigators planning to conduct clinical investigations of FDA regulated drug(s) or device(s) for an indication that does not appear in the approved labeling for the product. Depending on the origin of the funding for the trial (e.g. federal funding) regulations by the U.S. Department of Health and Human Services Office for Human Research Protections (OHRP), 45 CFR 46 known as The Common Rule, may also be applicable.

In most cases, institutional policies and guidance fall into two major categories: protecting human subjects and ensuring the integrity of the data from clinical investigations. This is true for all research trials.

All investigators in interventional drug studies must complete and submit FDA Form 1572 (21 CFR 312.50), which specifically outlines certain responsibilities and obligations including agreeing to personally conduct and supervise the investigation.

Investigational New Drug (IND) or IDE Applications

Some protocols may require the investigator to submit an investigational new drug (IND) or an investigational device exemption application. However, a sponsor-investigator may not be required to submit an IND for a study of a lawfully marketed drug if the criteria outlined in the FDA regulations at 21 CFR 312.2(b) for an IND exemption are met. Investigators should confirm if the protocol is exempt from this requirement by reviewing the regulations. If sponsor-investigators are uncertain if the exemption criteria are met, they should seek advice from FDA.

For trials involving medical devices, the Investigational Device Exemptions (IDE) regulation (21 CFR 812) must be considered. Under this regulation medical devices are generally categorized as significant risk or nonsignificant risk devices. Significant risk devices studies must have an IDE application approved by FDA before any research may begin.

Conduct Good Clinical Practice (GCP)

GCP is an international ethical and scientific quality standard for clinical trials with a primary objective of protecting human rights. Compliance with this standard helps to provide assurance that the rights, safety, and well-being of trial subjects are protected. FDA has adopted GCP as guidance for carrying out clinical trials. FDA regulations relating to good clinical practice and clinical trials include:

Monitoring and Reporting

Good Clinical Practice (GCP) guidelines also describe the requirements for quality management in clinical trials to further ensure the protection of participants and the reliability of trial results. Investigator-sponsors have specific responsibilities for monitoring trials to confirm the trial is conducted and the data generated, recorded, and reported are in compliance with the protocol, GCP, and the applicable regulatory requirement(s).

The methods used to assure quality should be proportionate to the risks in the trial and the importance of the information collected. Methods for monitoring clinical trials range from on-site data verification to centralized data monitoring using statistical analytics to identify areas of risk.

Investigators who do not comply with these regulations and standard operating procedures run significant risk of liability and federal investigation. The FDA has outlined a specific process for investigating non-compliant investigators that includes disqualifying investigators from further research.

The regulatory landscape is constantly shifting and can pose some challenges, particularly for new investigators. Working closely with regulatory experts through the steps, as well as taking courses on GCP, can minimize the risks, protect patients, and ensure research integrity.

Further resources

FDA Guidance for Industry: Investigator Responsibilities
https://www.fda.gov/media/77765/download

FDA Guidance for Sponsor-Investigators
https://www.fda.gov/media/92604/download

ACRP Guide to FDA Form 1572
https://acrpnet.org/2019/04/25/revisiting-the-form-fda-1572/

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.

Leveraging Benchmarks

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.

Additional resources:

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
  • pharmacists
  • laboratory technicians

You should also include any staff who should be notified in case of an audit, including contacts in:

  • medical records
  • risk management
  • compliance
  • administration

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.

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.

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[1] are examining how to enroll smokers in their studies. They are evaluating e-consents, online surveys and questionnaires, as well as smartphone-enabled devices.

 

Patient Enrollment

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

Electronic Consents

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[2] about insurance coverage of telemedicine visits demonstrate some shifts in reimbursement.

To monitor patients’ vital signs and other data in real-time, some investigators are turning to mobile apps and wearable devices. The use of these technologies presents challenges with regard to privacy. Many of these devices and third-party apps have their own user agreements that require careful review, as they may be in conflict with certain privacy requirements or the terms of use may need to be explained to patients during the informed consent process.

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.

[1] https://www.news-medical.net/news/20200930/Researchers-explore-remote-methods-for-conducting-smoking-cessation-clinical-trials.aspx

[2] https://www.statnews.com/2020/09/29/united-healthcare-anthem-telemedicine-coverage-insurers/

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.

Leverage technology

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:

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.

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.[1] Some universities have issued “urgent ramp-down of on-site, in-person research activities”[2] or are downright “suspending all non-critical on-campus research activities.”[3] 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

https://grants.nih.gov/grants/natural_disasters/corona-virus.htm

Global Impact on Clinical Trials

https://www.engage.hoganlovells.com/knowledgeservices/news/the-global-impact-of-covid-19-on-clinical-trials-and-countermeasure-development

 

[1] https://www.fiercebiotech.com/biotech/covid-19-outbreak-prompts-provention-to-pause-diabetes-trial

[2] https://provost.columbia.edu/news/covid-19-and-urgent-research-tasks

[3] https://drexel.edu/research/resources/coronavirus-preparedness-information/on-campus-research-activities-status-change/

Taking Advantage of NIH Funding Increases for Investigator-Initiated Clinical Research Requires Thoughtful Protocol Writing

Earlier this year, the National Institutes of Health (NIH) announced the approval of a budget appropriation bill for funding through September 2020. In it, the NIH receives $41.68 billion in funding, an increase of $2.6 billion from FY 2019. For NIH, the new budget appropriation includes $500 million for the All of Us precision medicine study and a $25 million increase for HIV/AIDS research. It also included a $350 million increase for targeted Alzheimer’s research, $50 million to support pediatric cancer research, and $212.5 million to increase funding for adult cancer research.

The 2020 appropriation includes grant funding for both early stage and clinical research. One of the challenges in grant submission related to clinical research is developing a well thought out clinical trial protocol that can meet both scientific and regulatory requirements. Some investigators, particularly ones earlier in their career, may feel daunted by the process of writing a protocol.

Having an easy-to-follow, step-by-step protocol-writing tool can promote adherence to regulations and streamline the institutional review processes. Many institutions have developed protocol writing templates for investigators. Unfortunately, many of them are basic word processing documents and can be unwieldy and long, frustrating protocol writers. A cloud-based, guided experience can assist both seasoned protocol writers and those new to protocol writing, such as medical residents.

Physician investigators and medical residents are not the only ones who may benefit from such a tool. Doctoral students in nursing, physical therapy and other allied health fields are discovering that to complete certification in their fields, they must participate in clinical research.

Additionally, a cloud-based protocol writing system allows closer collaboration with co-investigators or research advisors. By engaging collaborators early in the protocol-writing process, investigators benefit from the shared ‘creative thinking’ that is critical to scientific development.

As institutions, including medical centers, support residents and early career investigators, they may wish to consider a more robust solution than Word templates. In identifying and selecting a tool, they should consider the following questions:

  • Does the tool allow easy collaboration with mentors or co-investigators?
  • Is it a guided experience, offering assistance and education throughout the process?
  • Can it be customized to suit the requirements of the individual institution?
  • Does it maintain an audit trail of changes?

These and other critical questions can help institutions evaluate the best protocol-writing tools. By supporting investigators in medicine and allied health fields, institutions can realize the benefits of clearly-articulated protocols. This, in turn, may help increase opportunities for developing well thought-out investigator-initiated clinical protocols that can help strengthen a grant submission.

Interested in protocol-writing tools? Check out Protocol Builder by BRANY.

 

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

Informed consent

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.

Budget impacts

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

NEWS RELEASE

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[1] 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.

[1] 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.

Are Staffing Challenges Affecting Your Institution’s Research Profile?

Many institutions still struggle to recruit and retain the best talent for these challenging positions. A changing regulatory landscape, increasingly complex protocols and a litany of deadlines all contribute to a stressful environment for these employees. Additionally, salaries have remained largely stagnant, creating a general sense of disengagement.

Staff turnover can lead to interruption in workflow and management, often creating delays for study start-ups. With study coordinators often the primary contact with CROs, regulatory agencies and sponsors, the disruption and inconsistency in communication can have a negative impact on the relationship with these important stakeholders.

“We have seen situations at institutions in which an entire study was put on hold because a coordinator departed and there was no one to continue the work,” says Jill Filipelli, BRANY’s Clinical Trials Activation Team, Operations Manager, “This created quite a bit of consternation and frustration from the sponsor.” These institutions are at risk of losing future opportunities as selected study sites.

High turnover can be expensive for employers. A study published by the Society for Human Research Management showed that replacing an employee can cost up to 50 to 60 percent of the employee’s annual salary. If you add the cost to onboard and train a new coordinator in procedures and protocols, the cost of recruiting a new employee can be significant. Investing in retaining experienced talent can save in long-term costs associated with turnover.

Studies have shown that salary alone is not the key factor in retaining staff. According to a 2012 Centerwatch study, study coordinators are looking to advance their careers through professional training and promotions. Providing opportunities for education and training is a cornerstone to a successful staff retention strategy. Ongoing mentoring of CRCs can also encourage more engagement and job satisfaction.

Investing in the development of clinical research staff can yield results well beyond mitigating the hassle of hiring new employees. Having a consistent team also ensures consistency and smoother workflow to ensure the successful start-up and management of clinical research programs. This, in turn, stabilizes and improves relationships with CROs and sponsors when they are identifying research sites.

 

 

 

The Revised Common Rule and Informed Consent: Public Posting

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 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

The Revised Common Rule and Informed Consent: Broad Consent

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

 

Protocol Builder Launches Protocol Template for Social-Behavioral – Educational Research

BRANY announced today the release of a new research protocol template specifically designed to address the unique needs of social-behavioral-education researchers, as part of Protocol Builder®, a secure, cloud-based protocol writing application.

“Social and behavioral research is distinct from biomedical research,” says Jeffrey Cohen, PhD, a principal with HRP Consulting Group, also a division of BRANY. “The process of writing a protocol can be more subtle than an interventional drug study, for example.”

“Although historically many social behavior researchers have not developed full protocols for their research prior to submitting to an IRB, many institutions are now requesting social behavioral protocol development templates as research in this area continues to grow,” says Kimberly Irvine, Executive Vice President and Chief Operating Office for BRANY. BRANY now also has a social behavioral IRB as part of its comprehensive IRB service offering. This new template is a response to our customers’ requests for a tool that provides them with a more comprehensive approach to protocol development for social and behavioral research.

The specially-designed template provides a guided, step-by-step protocol-writing process for investigators who specialize in psychology, nursing, education and other disciplines that are focused on behavioral and social functioning. It is one of several standard and customizable templates offered through Protocol Builder®, including the new NIH IND/IDE template.

Protocol Builder® is currently in use at leading academic medical centers and universities as a tool to foster compliance with institutional protocol writing standards among their investigators, including residents and fellows.

Protocol Builder® is a division of BRANY, the leading provider of research support services to hospitals, academic medical centers and investigators. In addition to Protocol Builder®, BRANY offers a wide array of services designed to improve research efficiency and quality. These include IRB, human subject protection consulting and continuing education.

BRANY IRB Services

BRANY IRB, AAHRPP-accredited since 2006, has been providing high quality, customer service oriented IRB services to client for more than 18 years. BRANY IRB specializes in , single IRB (sIRB) for multi-site research, and SBER IRB review by a committee with expertise specific to social, behavioral and education research.   BRANY’s “Connected IRB” model has provided institutions with a customized solution that results in high quality human subject protection oversight, as well as efficiency for industry sponsored and investigator initiated research.

HRP Consulting

Through its consulting division, the HRP Consulting Group, BRANY provides institutions human subject protection and research compliance consulting services.

CITI Program

The Collaborative Institutional Training Initiative (CITI Program) at the University of Miami, also part of BRANY, is the leading provider of online research ethics education courses and materials. CITI’s web-based training materials serve millions of learners at academic institutions, government agencies, and commercial organizations in the U.S. and around the world. CITI Program now offers the CTSA created GCP – Social and Behavioral Research Best Practices for Clinical Research course.*  This course introduces GCP principles and discusses how they apply to clinical trials using behavioral interventions and social science research.