The Great Resignation — Managing the Impact on Research Teams
Among other things, 2021 will be known as the year of The Great Resignation, or in many sectors, the great retirement. Record numbers of employees left their jobs. Nearly four and a half million Americans left their jobs in September 2021, the highest number on record since the Bureau of Labor Statistics began collecting data 20 years ago. The numbers show a 40 percent increase over the same period in 2020.
The healthcare sector has not been spared. According to the report, 589,000 U.S. workers resigned or retired from health care and social assistance positions. A children’s hospital in Ohio recently put out a call for clinical volunteers to help support staffing shortages. A study in Utah in April that tested the sentiments of nearly 28,000 University of Utah Health system clinical and non-clinical faculty, staff and trainees found that 20 percent of respondents, 1 in 5, are considering leaving their professions.
Economists and pundits are untangling the possible reasons for this massive change in the labor market. Some suggest The Great Resignation is driven by massive burnout among workers. Others point to stagnant wages, lack of career growth opportunities, and challenging work conditions. Yet others suggest that employees who have been working from home simply do not want to return to the office and prefer the flexibility offered during the pandemic.
The trend may continue. A recent Gallup survey found that 48 percent of the working population in the United States is actively job searching. Studies show that the trend is driven by mid-career employees — those between 30 and 45 years old as well as those close to retirement age that decided to retire after the height of the pandemic. This can suggest a loss of critical experience and expertise, in addition to the drop in engagement and productivity.
Recruiting, hiring, and training new research staff is expensive and time-consuming. This effort may impact the ability of research sites’ to manage current clinical trials or even start new trials in 2022. The disruption in staffing also may pose risks, since much of the work requires a fine-tuned attention to detail that may be lost as staff including coordinators, research nurses, and principal investigators transition to roles outside of research or move to other organizations.
To mitigate these risks, leaders must address employee disengagement on multiple fronts — long-term and short-term. In the long term, research leaders need to evaluate how to retain and engage experienced workers to minimize turnover. In the short term, workers must be protected from overwork and potential burnout, and offered the opportunity to engage in meaningful work with flexibility.
To achieve this, research administrators and leaders can consider these strategies:
- Increase learning opportunities — Beyond the required training and certifications for clinical research coordinators and other staff, leaders should provide additional online learning opportunities. A June 2021 survey with Amazon, Gallup found that 57 percent of U.S. workers want to update their skills and 48 percent would consider switching jobs to do it.
Advanced training and “upskilling” can include courses in project management for clinical trials; preventing and identifying misconduct and noncompliance; financial management of clinical trials; subject recruitment and retention; statistics and data management of clinical trials; and specialty areas including regulatory compliance.
- Cultivate career development — The same Gallup study showed that the primary reason people change jobs is for career growth opportunities. Training can position early-career staff for additional responsibilities, which then provides research sites with a deeper bench of talent for advancement.
Managing clinical trials requires many administrative tasks that, while important, may be less professionally fulfilling. Having a clearly communicated path for career growth and advancement can incentivize employees to stay.
- Create flexible work environments — Starting and running clinical trials requires a high degree of staffing flexibility as workloads shift. Outsourcing the administrative burden can enable site staff to focus on strategic needs while filling in short-term gaps. The result can be more efficient resource management and consistency in research infrastructure.
The Great Resignation of 2021 shows no signs of slowing in the new year. Research sites must create and nurture environments for employee career growth and engagement to remain competitive.
The Future of Work and the Impact on Research Institutions
International organizations such as the World Economic Forum have been researching and analyzing the “future of work” and its implications for economies. Likewise, consulting firms have been predicting the important training needed to prepare workforces for new labor markets. Surveys of company leaders indicate an increasing need for employee upskilling and retraining.
The COVID pandemic and dizzying changes to our work environments accelerated the already-occurring changes in how we work. For research professionals, the changes have impacted how we start-up and manage clinical trials. The breakneck speed with which pharmaceutical companies developed, tested, and deployed COVID vaccines may have been a preview. The clinical trial community should understand the lessons learned from these expedited processes and consider how to prepare for “the next time.”
It remains to be seen which changes will remain for the long term. But some experts say that some permanent changes are inevitable, whether it’s remote patient visits, online collaboration, or remote digital monitoring.
Studies about the future of work tend to focus on the use of artificial intelligence and increased dependency on automation. There are human factors to consider, as well. Managers must define how to run hybrid teams and encourage resilience among workers. The World Economic Forum identifies major changes in three categories:
- Technology in the form of machine learning, artificial intelligence, and automation
- Ongoing learning and skill acquisition
- Talent mobility
This was supported by a report by McKinsey & Company, published in October 2020, that said workers in the life sciences had to double their efforts to focus on patients, leverage technology, and cultivate workplace agility.
Flexible work force
The ability to accommodate the ebb and flow of clinical research activities, or rapid redeployment based on shifting priorities, means that leaders need flexible staffing.
Hybrid work situations will require the need for cross-training among staff and the increased use of external resources to supplement internal staff. Highly responsive teams, augmented by expert hands-on external staff, can ensure sustainability of existing research projects even when new or urgent needs emerge.
Improving patient communication
The requirement to obtain informed consent of individuals before involving them in research is one of the central protections provided for under the HHS regulations at 45 CFR part 46 and 21 CFR 50.
The Revised Common Rule introduced new informed consent standards that focus on providing prospective research participants with information that a reasonable person would want to have in order to make an informed decision about participation in a research study. Additionally, the presentation of information to the participant must be organized and include sufficient detail to facilitate the participants understanding of why they may or may not want to join the research study.
These requirements, along with the shift to e-consent and other technologies, have changed not only the language of consent forms but also the process and workflow in obtaining consent.
This is just one example of many patient-centered shifts in the paradigm of clinical research.
Beyond the required certifications in Good Clinical Practice or foundations for clinical research coordinators, research institutions must offer ongoing upskilling opportunities for staff to keep them up-to-date on the shifting technology and regulatory landscapes of clinical research.
Even prior to the pandemic, online learning was dominating the professional development field. Hiring managers who wanted to cultivate a more diverse and agile workforce were using online solutions such as CITI Program to ensure their skills were up to date.
Leveraging technology for better collaboration and improved workflow
Writing a protocol for a clinical trial has become a complex team sport requiring multidisciplinary input from various sources. Researchers are collaborating with colleagues at their own or other institutions, across clinical disciplines.
The protocol-writing process — from version management to IRB review — can be cumbersome. The use of paper-based systems, or even email, can result in confusion or delays. The result can mean incomplete IRB submissions and frustration for investigators.
Cloud-based guided applications, such as Protocol Builder, can expedite the process by fostering communication and teamwork. These systems build teaching into the writing process, which is essential for residents or new investigators. A complete and compliant protocol submission can result in a smoother IRB review process.
While no one has a crystal ball into the future, many organizations and foresight consultants are in general agreement that the workplace is undergoing a paradigm shift. Research institutions are not immune to these major changes, particularly if they focus on the key areas of change — mobility and flexibility, increased use of technology, and ongoing learning and upskilling.
FDA Updates Guidance for Clinical Trials During COVID-19 Pandemic
In March 2020, as governments around the world were issuing large-scale lockdowns, health facilities shifted their efforts to addressing critical needs of patients while trying to maintain the safety of staff. Clinical trials ended or were paused, and researchers allocated their attention and resources to understanding and managing the novel coronavirus.
To assist researchers, IRBs, and sponsors, the FDA issued guidance last year on the conduct of clinical trials during the COVID-19 pandemic. The guidance aimed to help institutions protect clinical trial participants, maintain compliance with Good Clinical Practice, and ensure data integrity of the research. Among the many challenges brought on by COVID-19, some of the most vexing logistical challenges came from quarantines, site closures, travel limitations, and interruptions of the supply chain for investigational or other products. In addition, institutional leaders have had to address considerations if site personnel or trial participants became infected with COVID-19.
The FDA recently updated this guidance, in August 2021. This is a high-level review of some of the issues addressed in the guidance.
Deviations from a protocol may be necessitated by changes to public health recommendations both at the national and local levels. Also, deviations can occur in the case of exposure, a positive test, or diagnosis of a trial participant.
Deviations can include a change in how patients are monitored — from in-person to remote visits, for example. COVID-19 has increased the acceptance of these alternative methods of monitoring, reducing unnecessary travel and risk of exposure for participants. For the safety of participants, sponsors may consider options such as phone calls, virtual visits, or even remote monitoring devices.
Some changes to the protocol or investigational plan are intended to minimize or eliminate immediate hazards or to protect the life and well-being of research participants. In these urgent cases, deviations may be implemented without IRB approval or before filing an amendment to the investigational new drug (IND) or investigational device exemption (IDE) However, they are required to be reported afterwards.
Investigators should work closely with IRBs to ensure policies and regulatory requirements for reporting deviations are followed and, when needed, develop plans or procedures to prioritize reporting of deviations that may impact the safety of trial participants.
Additional Screening Procedures
Institutions may require COVID-19 screening of clinical trial participants. In these cases, the screening does not need to be reported as an amendment to the protocol, even if done during clinical study visits.
On the other hand, if the sponsor is incorporating the data collected as part of a new research objective, it should be reported as a change to the protocol. This additional protocol-driven screening should also be considered in the clinical trial budgeting process.
The Importance of Documentation
Sponsors and clinical investigators should document how restrictions related to COVID-19 led to the changes in study conduct and duration of those changes. They should indicate which trial participants were impacted, and how those trial participants were impacted.
Some changes, such as an adjustment in a study visit schedule, may lead to missing information. In those cases, it is important to capture in the case report what specific data is missing and the reason for its absence.
Other items that sponsors should document:
- Contingency measures implemented to manage disruptions due to COVID-19
- A list of all participants who were impacted by COVID-19-related study disruptions, and how they were impacted
- Analysis of how contingency measures may have impacted safety and efficacy results
Protecting Data Integrity
Sponsors that anticipate that changes to the protocol will impact data management procedures or statistical analysis plans should coordinate with their respective FDA review division. This includes situations in which the efficacy endpoints may be impacted. For example, assessments may be conducted virtually instead of in-person. Any modifications to the data management or statistical analysis plan but also receive IRB review and approval.
Questions and Answers
The guidance also contains an appendix with 28 questions along with detailed answers for each question. Some of the topics covered include:
- re-monitoring after pandemic related restrictions are lifted
- exclusion criteria for “investigational medical products”
- collecting electronic signatures and Part 11 compliance
- reviewing IND safety reports
Twenty months after the first COVID-19 case was confirmed in the United States, researchers are still trying to understand the long-term impact on non-COVID clinical trials. Researchers and clinical trial professionals have had to demonstrate resilience, flexibility, and adaptation in the face of uncertainty and a changing epidemiological landscape.
The primary guiding principle throughout the guidance is to ensure the safety of clinical trial participants.
Proposed Cures 2.0 Act May Have Implications for Researchers
Members of the U.S. House of Representatives have introduced updates to the 21st Century Cures Act, which was signed into law in December 2016. The proposed legislation coincides with a detailed concept paper the White House published Tuesday in Science Magazine outlining their vision for the new research agency.
The 21st Century Cures Act, known as “Cures”, was initiated to modernize the U.S. healthcare system. The far-reaching law included provisions to advance precision medicine, accelerate the development of new medical products, and bring new innovations to patients more efficiently.
The new bill, called the Cures 2.0 Act would create an Advanced Research Projects Agency for Health, or ARPA-H, and would authorize more than $6.5 billion to run the agency. The mission of ARPA-H will be to speed transformational innovation in health research and speed application and implementation of health breakthroughs.
Under the terms of the lawmakers’ proposal, the new ARPA-H would be largely modeled after the military’s Defense Advanced Research Projects Agency, or DARPA, which has been responsible for successfully developing some of the most significant technological advancements of our time, including the Internet, GPS and self-driving cars. DARPA initially funded mRNA vaccine technology, which led to the development of a highly effective COVID-19 vaccine in record time that’s helped slow the spread of the virus both in the U.S. and abroad.
While the 21st Century Cures Act sought to improve how new drugs and treatments are researched and developed in the U.S., Cures 2.0 seeks to improve how those new treatments and therapies are delivered to patients.
The bill provides $25 billion to independent research institutions, public laboratories and universities throughout the country to continue their work on thousands of federally-backed projects. In addition to the funding, some of the sections of the legislation will have direct implications for researchers, specifically:
- Increase diversity in clinical trials.
- Require FDA to expand the collection and use of “real world evidence” to aid in the development of new, patient-focused treatment approaches.
- Require study sponsors to collect patient experience data in clinical trials.
- Ensure coverage for clinical trials under existing standard of care: allows Medicare to cover the costs of their beneficiaries in PCORI-funded clinical trials
- Increase access to telehealth services for patients covered under Medicare, Medicaid or the Children’s Health Insurance Program (CHIP) — possibly opening opportunities for more remote clinical trials.
- Provide grants for innovative clinical trial design and patient experience data to further build the science in these areas.
- Minimize or remove requirements for IND applications to initiate accelerated approval if sponsors meet proper criteria.
- Allow for use of evidence such as clinical evidence, patient registries, or other real-world evidence, to fulfill post approval study requirements to confirm the predicted clinical benefit of a therapy.
Reps. Diana DeGette (D-Colo.) and Fred Upton (R-Mich.) plan to hold roundtables about their proposal in June and July with the aim of releasing a final bill after Congress returns from its August break, according to reports.
ARPA-H Fact Sheet (https://upton.house.gov/uploadedfiles/final_cures_2.0_2-pager.pdf)
A section-by-section summary of the bill https://degette.house.gov/sites/degette.house.gov/files/Cures%202.0_DD%20SxS_FINAL1.pdf
Article published in Science (https://science.sciencemag.org/content/early/2021/06/22/science.abj8547)
Restarting Research Projects and Programs
The COVID-19 pandemic had significant impacts on clinical trials and research programs. According to researchers at Penn State, over 80 percent of clinical trials were suspended between March 1 and April 26, 2020, mostly due to the pandemic. The impact was more substantial for government or academic-funded studies than for sponsored trials, according to their study, which was published in March 2021. Among other concerns, researchers cited the challenges associated with recruiting and following up with patients.
Research leaders assembled task forces and started planning for the re-start of clinical and lab research as early as last summer. With unpredictable surges in cases in different states, the restart of research has not been uniform. This has required a high degree of flexibility among leaders and staff.
As vaccination programs roll out across the country, medical center campuses are updating their return-to-campus policies to accommodate the shifting landscapes. Physical distancing, use of masks and encouraging staff to continue remote meetings are still part of many campus policies. Each institution has to assess risk based on local risk factors and patient populations. Research professionals must constantly revisit processes and procedures for starting or continuing clinical trials programs, as well.
For industry sponsored studies, many trials shifted to remote monitoring and implemented telemedicine visits to minimize exposure to the coronavirus. Most institutions prohibited sponsor representatives from conducting in person site initiation visits and clinical trial monitoring. These restrictions are also beginning to be lifted.
Evaluate and Re-Allocate Resources
Campus closures were disruptive for staff as they often shifted their focus to supporting COVID activities on medical campuses. Some staff may return, others not. Turnover among clinical research coordinators was already high before the pandemic, and uncertainty about the future may have exacerbated this.
Recruiting and training new clinical research coordinators can be time-consuming and challenging under current circumstances. Research teams may need flexible staffing, or to ramp up activities quickly with limited staff. In these cases, it may be prudent to consider outsourcing much of the administrative and compliance work associated with clinical research.
Managing the many aspects of the COVID-19 pandemic this past year has also depleted financial resources at many institutions. Institutions have implemented hiring freezes because funding is scarce. Budgets for 2021/2022 are being cut all around including areas such as research administration.
Another question to consider: as restrictions are lifted to allow more clinical trials to begin again, and to open organizations for in person monitoring and site initiation visits will staff be available to support these initiatives?
Review Protocols for Deviations and Violations
It is important to understand the difference between a protocol deviation versus a violation, as there are implications for reporting requirements and IRB review.
Generally speaking, a protocol deviation occurs when, without significant consequences, the activities on a study diverge from the Institutional Review Board-approved protocol. For example, a patient may have missied a visit window because s/he is traveling.
A protocol violation is more serious. It refers to a divergence from the protocol that materially:
- reduces the quality or completeness of the data
- makes the Informed Consent Form inaccurate, or
- impacts a subject’s safety, rights, or welfare
If there are changes to the protocol, then IRBs may need to review updated patient consent forms. Additionally, some institutions are implementing e-consents and other technologies.
Communication with participates goes beyond consents. As return-to-campus protocols are modified, staff must advise research participants of any changes. For example, if a study moved to telehealth visits, and is now re-opening to in person visits, participants should receive the campus COVID guidelines prior to their next visit. Coordinators may need to communicate with participants regarding options that were implemented in response to COVID-19, and whether they will still be options as in person visits resume.
Identify Potential Budget Implications
Changes in protocols, methods of obtaining consents or conducting follow-up visits are just three ways in which a study budget can be impacted. Every change or accommodation to updated policies and procedures should be checked against the budget to ensure accuracy and appropriate reimbursement.
Experts are still debating what the future of work — and therefore, the future of clinical research — may look like post-pandemic. Regardless of the short- and long-term implications, it is essential for research staff to remain diligent and flexible in overseeing and updating procedures and policies.
Guide to Remote Audits
The United States reached the one-year anniversary of the first confirmed case of COVID-19, on January 15. Even now, as the rollout of vaccinations is underway, institutions are still facing campus and facility closures. We cannot underestimate the impact of COVID-19 on clinical trials and the research community. Institutions have had to refocus resources toward pandemic-related clinical care and research, which has caused delays, disruptions and cancelations of research in other clinical areas. Research coordinators and support staff continue to work remotely or in hybrid work situations.
Despite this, research professionals have demonstrated remarkable resilience and flexibility in adjusting to the new landscape. Over the last year, institutions have leveraged technologies to continue or start up clinical trials. Telemedicine has increased opportunities for remote consent and virtual study visits.
Restrictions on travel, in-person visits and access to research offices forced federal regulators to scale back their in-person surveillance activities, while increasing their remote audits to gauge compliance with Good Clinical Practices (GCP), Good Manufacturing Practices (GMP), and human subject protection (HSP). Investigators must be prepared for announced or unannounced inspections, particularly remote reviews.
A variety of situations can trigger an FDA inspection, from a serious adverse event (SAE) to reported violations of protocols. Just as your research team should be well prepared for in-person inspections, so should you be prepared for a remote visit. These are some of the areas where your team can prepare. In some instances, your team should coordinate with the IT department to ensure a secure, yet easily accessible, repository of information.
Gather and centralize stakeholder contact information
The names and contact information (mobile phones, pagers and email) of all key staff should be in a central place, such as a spreadsheet. This record can include:
- principal investigator (your materials should include the PI’s CV)
- clinical research coordinators
- laboratory technicians
You should also include any staff who should be notified in case of an audit, including contacts in:
- medical records
- risk management
Your contact list should include your primary contact at the study sponsor and/or CRO.
Digitize study documents
Depending on the requirements of your institution or the study sponsor, you may want to consider scanning regulatory documents and keeping them in a secure cloud-based file system. Consider including these items:
- IRB documentation, including the approval letter and amendments
- consent form (at least the latest version)
- study reference manual
- study protocol(s)
- sponsor instruction manuals
- policies and procedures
- roles and responsibilities for each of the key team members
- correspondence with the sponsor
- certifications (for example, for the laboratory)
- other essential documents as per Good Clinical Practice (GCP)
You should be prepared to upload participant documents such as signed Informed Consent Forms, Case Report Forms, and source documents to a file sharing application, following institutional requirements of redacting protected health information, if applicable. You may want to explore with IT granting auditors remote read-only access to the Electronic Medical Record for the participants selected for the remote audit.
Prepare a plan with stakeholders
The nature of remote audits may require more time to prepare requested documentation. It is important to prepare a plan and to educate your internal stakeholders on the procedures and areas of responsibilities in the event of an audit. A mock audit can test everyone’s response and identify risks and gaps. Don’t forget to include the IT department and staff in other departments who may need to play a role.
In the case of paper documents that are not scanned and uploaded in advance, you should have a plan for doing so upon request of the auditors. Identify a secure and HIPAA compliant storage platform and the mechanism by which you can obtain and upload those documents remotely that adheres to the institutional policy.
Be prepared to deliver a virtual “live” walk-through of facilities. Identify who will provide the tour and the technology necessary to do. Ensuring strong Internet connectivity in those areas, such as basement laboratories and other potential weak Wi-Fi zones can ensure a smoother experience for everyone.
It’s likely that remote work and, therefore, remote research surveillance will be part of the workflow for some time. Preparing for a remote audit can decrease stress and ensure clear communication among all the stakeholders.
Is Your Institution Prepared to Identify Exempt Research?
The disruption of clinical research as a result of COVID-19 cannot be overstated. Virtually everything about developing protocols and starting clinical trials has been upturned. In some cases, trials have been closed indefinitely. Others have been delayed or streamlined. Much of the interaction, such as IRB review meetings, has been shifted online, decentralized or outsourced to free up resources in the fight against the pandemic.
Anecdotally, we have observed a change in the types of protocols submitted for IRB review, as many investigator-initiated trials have pivoted toward better understanding of COVID-19. At BRANY, we have seen an influx of exempt research — protocols that pose minimal risk and fit into pre-specified categories that are exempt from IRB review. This type of research still requires a determination that it meets criteria for exemption. The regulations do not specify who at an institution may determine that research is exempt under 45 CFR 46.101(b). However, the U.S. Office for Human Research Protection (OHRP) recommends that, because of the potential for conflict of interest, investigators not be given the authority to make an independent determination that human subjects research is exempt. The IRB is often tasked with making exempt determinations.
Institutions should develop standards and procedures for determining research is exempt. However, this can be complex and complicated as exempt categories must be interpreted for specific situations. In developing these policies, OHRP recommends the following:
• Develop standardized mechanisms for collecting sufficient information to make the determination. This can include checklists, standard operating procedures and requirements for training.
• Policies should clearly define who has authority to make these determinations and provide sufficient training for those people.
• Define categories for exemption and use them in making the determination. This is useful in case of audit, but also helps the institution to establish policies.
• Provide clear guidance to investigators about federal and institutional guidelines.
This last point is crucial, as there is no federal mandate that anyone other than investigator make the determination that a research study is exempt. Some institutions may be tempted to expedite research and avoid delays by allowing investigators to make these determinations. The provision of detailed checklists, or the use of a guided protocol writing tool such as ProtocolBuilder, may help the investigator in these cases. The OHRP, and we at BRANY, strongly advise that someone other than the investigator make this determination in order to avoid possible conflict of interest.
Research institutions and academic medical centers must continue to adjust to the rapidly shifting landscape brought on by COVID-19. Resources have focused on understanding the pandemic and have been funneled toward both interventional and observational research in this area. This has resulted in a possible increase in investigator-initiated studies that may be considered exempt. Institutions may need to review their policies and procedures for making these determinations to ensure they are both in compliance and, more importantly, continue to protect human subjects.
Trends: What We Are Watching in 2021
We know we are not alone when we say we are happy to put 2020 behind us. It was a challenging year for everyone, and we look forward to better days ahead. Despite the difficulties that the research community faced, we witnessed remarkable flexibility, resilience and creativity in dealing with significant hurdles. Last year lent new meaning to the phrase “hindsight is 2020.” In this article, we look ahead at 2021 and share the issues that we will be monitoring.
Diversity and inclusion in clinical trials
The COVID-19 pandemic highlighted serious racial and economic disparities in health care. Some racial and ethnic minority groups have been disproportionately affected by COVID-19. Conditions in the places where people live, learn, work, play, and worship affect a wide range of health risks and outcomes, such as COVID-19 infection, severe illness, and death. Long-standing inequities in social determinants of health that affect these groups, such as poverty and healthcare access, are interrelated and influence a wide range of health and quality-of-life risks and outcomes.
Likewise, racial and ethnic minorities are underrepresented in clinical trials. The research community, which includes industry sponsors and government agencies, is actively pursuing strategies that address disparities in clinical research. The FDA issued guidance in November aimed at enhancing diversity and encouraging inclusivity in medical research, specifically in the development of medical products. The industry trade group PhRMA adopted Principle 6, Commitment to Enhancing Diversity in Clinical Trial Participation, aimed at enhancing racial and ethnic diversity among clinical trial participants, with an effective date of April 14, 2021.
We will be watching how industry-sponsored and investigator-initiated trials implement strategies for increased inclusion.
Re-starting Clinical Trials
The pandemic led to the halting of hundreds of clinical trials. Lockdowns and other mandatory public health orders forced research staff to work from home and made in-person patient visits nearly impossible. Additionally, staff resources were redeployed to shore up shortages and support hospitals’ responses to the surge in COVID-19 cases in communities in the U.S. and around the world.
For some patients, particularly with end stage disease, the suspension of clinical trials had serious implications. Likewise, enrollment for new trials staggered as patients were wary of visiting any medical facilities. In an editorial in JAMA, researchers said “Mitigation efforts [against COVID-19] interfere with all aspects of a successful clinical trial: efficient accrual and randomization, intervention adherence and delivery, and outcome collection.”
Even now, research institutions are grappling with solutions to reduce the impact of fluctuating and shifting public health mandates on existing trials. Investigators continue to evaluate how to re-start trials safely.
Increase in Observational Trials
Investigators have immense opportunities to design and implement investigational trials evaluating patient outcomes and long-term effects of COVID, as well as different treatment modalities. Additionally, researchers may consider trials evaluating various aspects of the different COVID vaccines currently on the market as well as other that are in the development and approval pipeline.
Opportunities for social-behavioral-education research
Stay-at-home orders and increased isolation, negative impacts on the economy and lost jobs, not to mention a daily barrage of dramatic news and social media coverage, have led to an increase in stress and anxiety. The pandemic also led to a disruption in mental health services.
We are still learning what the long term social and behavioral impacts will be. But we expect to see an increase in studies to evaluate this.
Remote Monitoring and Decentralized Clinical Trials
Since the pandemic began, over half of all active clinical trials are using remote and virtual support, according to a study by The Tufts Center for the Study of Drug Development. We expect to see the continued use of telemedicine, remote monitoring and virtual IRB meetings and reviews.
Research professionals will continue to make adjustments to how they run research programs. Many institutions may need to make policy decisions in the absence of specific regulatory guidance.
In September 2018, the Clinical Trials Transformation Initiative https://www.ctti-clinicaltrials.org/projects/decentralized-clinical-trials defined decentralized clinical trials (DCTs) as those executed through telemedicine and mobile/local healthcare providers (HCPs), using procedures that vary from the traditional clinical trial model. For example, the investigational medical product is shipped directly to the trial participant).
The research community may need to continue to develop awareness and understanding about DCTs and/or hybrid trial designs, and what is in the best interest of patient safety as well as research integrity.
Using Digital Technology and Telemedicine in Clinical Trials
The trend toward digital technology, such as health tracking devices and virtual clinic visits, had started before COVID. The pandemic accelerated the implementation of these technologies to allow study participants to sign consents, submit vital statistics and data, and communicate with clinical research coordinators and investigators — all from the convenience of their home.
We are loath to make any predictions in this most unpredictable time. The story of COVID and its impact on research is still unfolding. With that, we plan to continue monitoring these issues and offering support to clients that are navigating these uncharted circumstances.
Happy new year from the team at BRANY.
How COVID-19 Has Impact Clinical Trial Budgeting
As COVID-19 swept across the United States earlier this year, many research centers found themselves pausing or stopping clinical trials and shifting their work from an office or clinic to their homes. Clinical research staff pivoted their focus to support the COVID-19 response, or to launch critical studies focusing on COVID-19.
As some research staff return to campus, research sites are reviewing their study budgets and making important adjustments. We have outlined some of the key areas that may have clinical trial budget impacts.
Without the ability to visit campuses in person, sponsors must conduct monitoring visits virtually and remotely. It may seem like this is less time consuming and convenient. In fact, it may take more time and coordination to prepare medical records to review remotely from the research site perspective.
Study coordinators must collaborate with their institution’s IT teams to develop HIPAA-compliant remote access for sponsor or CRO study monitors. Within each institution, there may be many security steps that must be achieved prior to granting access to external parties. It can even be more complicated when there is a lot of staff turnover; monitors can change frequently during the research study lifecycle. In some cases, research staff might not have the proper equipment at home to access and/or transmit records. Research staff may have to print or scan medical records, then redact them and send them securely to the monitor.
Research sites should have their staff carefully track time spent on the extra steps and be sure to account for added time and effort in their budgets. Under pre-COVID circumstances, sponsors often provided arguments for not covering monitoring visits as it was considered a part of doing business. However, in the case of remote monitoring, coordinators and/or analysts should have a conversation about including the extra staff time and effort in the budget. This should include the time and effort of the IT department.
Telemedicine and Its Limits
For the sake of patient safety and whenever possible, office visits have shifted to virtual visits over the phone or videoconferencing. For patients in clinical trials, it could include engaging with the attending investigator, or a consultation with a nurse or coordinator. It is important to keep track of who participated in the virtual visit and to consider negotiating virtual visits as an item to be invoiced to the sponsor if the visit is not already covered as part of the sponsor’s budget. Keep in mind the time and effort of IT, or cost of HIPAA-compliant telecommunications technology to establish secure communication pathways among the patient, the investigator and research staff, for the purpose of the research study. If you are using online meeting platforms, such as Zoom or Microsoft Teams, there are costs associated with these applications as well.
In some cases, the protocol may call for a specific procedure such as IV drug administration. In this case, a visiting nurse or a contracted home health service may have to visit the patient’s home. The need for such a service should be identified and the logistics should be discussed with the sponsor. Budgets should include these visits as well as any costs for contracting and coordinating home health services.
COVID-19 Safety Measures
In some institutions, on-site staff are undergoing frequent COVID testing, sometimes twice a week. They also have had to stock up on personal protective equipment (PPE). As sites return to meeting study participants in person the use of PPE may increase. Consider including costs for some PPE supplies in your study budget when in person visits are required.
Many research coordinators shifted their focus to COVID-19-related projects. Many of them are now turning their attention back to research that had been put on hold, or on emerging new research projects.
Institutions have a mix of staff working at home and working in clinical environments. Administrators are encouraging more virtual meetings and contactless interfaces. This leads to a higher reliance on IT’s involvement in research to provide secure networks and communication. This, also, may mean a higher level of coordination with pharmacies, radiologists, and other clinical staff.
The return to campus and the restart of many trials requires a close look at budget to evaluate if there are any anticipated COVID-19 impacts, even if the study is not specific to the pandemic.
Lessons Learned (so far) in COVID-19
Even as communities start the process of evaluating re-opening, many experts believe that a new normal will be with us for a long time. Physical distancing, face masks and ubiquitous alcohol gel will be part of daily life. The risk of recurrence spikes also looms ahead and threatens a return to stricter “stay at home” orders. Health care and higher education institutions continue to evaluate risks and will likely continue to encourage employees, including IRB and research administration staff, to work from home in order to maintain physical distancing. Research office staff have made incredibly quick adjustments in real time as the pandemic made its way through the United States.
In assisting our partners and clients make rapid changes, we learned some lessons we believe will help research institutions be more resilient in the months and even years to come.
Prepare for the unexpected
Disaster planning and business continuity are required for organizations receiving National Institutes of Health (NIH) funding. But even non-NIH funded research institutions should have robust business continuity plans in place. The elements of a disaster plan include issues such as data security and protecting human subjects.
Many organizations scrambled to get their staff up and running from impromptu home offices. From installing and learning video conference platforms to having documentation securely available online, many research professionals quickly adapted to new ways of working and collaborating despite the learning curve.
Research institutions and investigators should consider building in these technologies as a part of their daily operations:
- Web-based collaborative protocol-writing tools
- Electronic Research Protocol Management Systems and Clinical Trial Management Systems
- Online training for research staff, particularly for operations and regulatory compliance
- Secure online meeting/video conferencing applications
- Secure cloud-based document storage for regulatory materials and other essential documents
Build in flexibility
Many research institutions pivoted their resources toward COVID-19 research efforts. This means that internal resources are unavailable for ongoing work or pending projects. Being able to shift that work to external resources, including IRBs, allows for flexibility to respond quickly as situations evolve.
External IRB partners should offer processes and procedures for running IRB meetings virtually in compliance with regulatory requirements. They should also hold frequent meetings, with the ability to hold ad-hoc meetings as needed.
Other functions can be outsourced to strategic partners, particularly when rapid turnarounds are required. These include the development and management of study budgets, coverage analysis, and clinical trial agreement support.
Select the right partners
The historic scope of impact on the research community at every level demonstrates weaknesses in every system, including partnerships. As with any disaster, communication is often the first thing to fail. Tightly synchronized communication with responsive partners who act as an extension of the research team can be the difference between an inconvenience and a very costly mistake.
Research institutions have demonstrated great resilience in their response to COVID-19, and have continued to focus on human subject protection throughout their efforts. There is talk of a “new normal” in the aftermath of the pandemic. These lessons learned can help institutions retain the integrity of their research while remaining responsive to what may be a long-standing landscape in the months or years to come.
Chart Review Studies During and After a Pandemic
The current global pandemic combined with electronic medical records and data visualization technologies have resulted in unprecedented advances in real-time tracking of SARS-CoV-2, the virus that causes COVID-19, across countries, states and local communities. As the situation evolves, there will be ample opportunity and increased need for both retrospective and prospective COVID-19 research studies that involve the review of medical records.
The rapidly evolving situation in this global pandemic requires investigators to design and write protocols quickly for IRB review. A guided protocol-writing experience, as with ProtocolBuilder, streamlines the process, ensures regulatory and institutional compliance, and facilitates collaboration among researchers.
In medical record review studies, also called a “chart reviews,” a researcher may collect and analyze information that was originally collected for a different purpose, also referred to as a secondary use of data. It often involves the collection of data from medical records in order to evaluate possible relationships between different variables and specific outcomes measures. An investigator may assess biomedical, treatment or demographic variables by reviewing various elements of a medical record. These may include lab results, physician or summary notes, admission and discharge summaries, etc.
Chart review studies can also be designed to collect prospective data, meaning the patient data does not exist at the time the protocol is submitted to the IRB for initial review. While many chart review protocols may qualify for a determination of exempt status from the IRB or expedited IRB review due to the minimal risk to research subjects, these studies are still subject to IRB review and HIPAA privacy protections. A guided and structured protocol-writing experience can accelerate the process while enhancing compliance, supporting collaboration, and saving time.
A chart review study protocol will generally include the following key elements:
- A synopsis — includes the objectives and high-level summary of the study elements, including a study flow chart
- Introduction and background — includes the protocol statement of compliance
- Rationale — includes the problem statement, risks and benefits
- Literature review — a synthesis of the current literature to establish the relevance of the problem and description of the literature that supports the need for the study
- Research design and methods — includes the study population and duration of the study. For chart reviews, a date range that indicates the timeframe for which records will be queried (e.g., a review of all ER visits between 1/1/2020 and 7/1/2020)
- Data collection and handling — includes a plan for maintaining subject confidentiality and privacy, how data will be collected and stored
- Statistical analysis plan — how the data will be analyzed to achieve the objectives
Chart review protocols are emerging as an important methodology in understanding COVID-19. Given the rapidly-developing nature of the global pandemic, the need for prompt writing and review of these protocols is critical to the ongoing effort to understand the situation.
ProtocolBuilder, a cloud-based research protocol-writing tool, can help improve the quality and consistency of clinical research protocols to make internal and IRB review processes more efficient.
Research Study Design
Research and HIPAA Privacy Protections (part of Comprehensive CIP Course for Advanced Learners)