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.
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.
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.
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 are examining how to enroll smokers in their studies. They are evaluating e-consents, online surveys and questionnaires, as well as smartphone-enabled devices.
Historically, patient enrollment in clinical research has been a significant challenge. According to research by the National Institutes of Health, 80 percent of clinical trials fail to reach their enrollment goals within the prescribed timelines. Some sites fail to recruit a single participant.
Social media is a promising way to recruit potential research subjects. With its current ubiquity, social media enables researchers to reach broad populations and target subjects based on personal information. They can also reach physicians and other clinical practitioners to inform them of new trials.
However, there are important risks to manage, including privacy and transparency. Researchers who join online patient communities — for example, those focused on a particular diagnosis — should be clear of their role.
Learn more about Social Media and Research Recruitment in this webinar: Citi Program course informed consent and clinical investigations a focus on the process
Obtaining informed consent via electronic methods involves more than just video conferencing technology. E-consents require an adjustment in processes, which can be an adjustment for research coordinators or others obtaining consent. Proper training on process is critical to ensure informed consent is obtained appropriately and the rights and welfare of human subjects are continually protected.
Implementing e-consent also requires assurance that the technology platforms are in compliance with FDA requirements for electronic signatures. Institutions must consider issues such as privacy and data security.
Learn more about remote informed consent: https://www.brany.com/telehealth-clinical-research-and-informed-consent/
Virtual Patient Visits and Wearables
Investigators who are writing protocols must consider opportunities for virtual patient visits that will minimize exposure to clinical environments such as hospitals and clinics. The use of telemedicine technologies has exploded in 2020, as clinicians worked to maintain continuity of care during lockdown.
One critical element to consider for virtual patient visits is to include them in the budget. Recent news reports about insurance coverage of telemedicine visits demonstrate some shifts in reimbursement.
COVID-19 presented many challenges to clinical researchers. But it also offered many opportunities to revolutionize how investigators think about writing protocols, and how patients can enroll and participate in them. The landscape continues to shift rapidly, and requires careful monitoring to ensure both compliance and patient protection.
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.
The Critical Issues Sites Need to Track During a Clinical Trial
Congratulations! You have gone through all the necessary steps to launch a clinical trial. Now it’s time to move on to the next one, right? Wrong! A successfully managed clinical trial requires ongoing tracking throughout its duration. Careful tracking ensures your research organization remains compliant and that your site is compensated properly for the study.
Follow our series on the key critical issues you need to track throughout a clinical trial.
Part One — Protocol amendments
This is likely one of the most common and time-consuming of the issues that require tracking. A Tufts University study found that over half of sponsored studies have at least one significant amendment.
Protocol amendments are inevitable, and some trials undergo multiple amendments throughout their duration. But some revisions are so significant it could feel like starting all over again.
There are generally two kinds of protocol amendments — administrative updates and substantive protocol revisions. Administrative changes are typically minor, and may involve grammar, wordsmithing, punctuation or small editorial changes. Significant amendments are any changes that may impact the safety of participants, and can include any change to the design of the protocol, including:
- Change to the dosing or duration of participant exposure to a drug
- Change to the design of the protocol, such as the inclusion or exclusion criteria or the addition of treatment arms
- Addition of new tests or procedures
IRB review and approval is required in order to carry out the visits and procedures that are part of the amended protocol. IRBs often require the following information when submitting an amendment:
- A description of the differences between the original protocol and the amendment
- Revisions to the informed consent, if applicable
- Revisions to any marketing or patient recruitment materials
Protocol amendments can impact patient recruitment efforts. In fact, some protocol amendments may also affect a site’s ability to enroll if there are significant changes to inclusion or exclusion criteria. Often the consent form must also be revised to reflect the changes to the protocol. Patients may need to be re-consented with the updated, IRB approved version of the consent form so they can be made aware of changes in protocol procedures.
Depending on the scope of the protocol amendment, your research site should review the study budget, as the necessary procedures may have changed or new procedures and visits may have been added. In our experience, amendments have an impact in roughly half of all study budgets. A full review of the budget, and possibly a revised Medicare Coverage Analysis, may be necessary.
Create a checklist
The more you prepare and plan for protocol amendments, the smoother the process to implement the amended protocol. The use of a checklist or systematic approach will ensure that no steps are overlooked.
Whenever there is a protocol amendment, clinical research coordinators should make sure they update the following:
- IRB/IEC and other regulatory submissions
- Informed consent documents, including oral consent scripts
- Marketing, advertising or recruitment materials
- Sponsor contract, particularly if there is an impact to the budget, and coverage analysis, if applicable
Studies have shown that protocol amendments can impact the cost and duration of clinical trials. But with some careful preparation, clinical research coordinators can ensure a smooth administration of the changes.
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