Feature: Clinical Trial Management in the Post-Pandemic Era: Reflections of an Investigational Drug Service on the Past Two Years

Jennifer Murphy, PharmD, BCOP
Senior Pharmacist, Oncology & Investigational Drug Service Investigational Drug Service, Cancer Center
Assistant Clinical Professor, UC San Francisco School of Pharmacy
Department of Pharmacy Services, UC Davis Health System
Sacramento, CA

The COVID-19 pandemic has fundamentally changed the operation of clinical trials over the past two years. The extent of the pivot and the rate of change in operations varied amongst clinical trial centers and Investigational Drug Services (IDS) as the COVID waves rippled across the country. While there have been numerous lessons learned by all, this unexpected impetus has altered the landscape of how clinical trials will be conducted in the future as we move into the post-pandemic era.

For those us who practice in an IDS pharmacy or manage patients enrolled in clinical trials, we now begin to reflect upon the past two years. It is important to evaluate which of the new strategies that were implemented hold enough value to continue in the post-pandemic landscape. Many new workflows and approaches were adopted: clinical trial patient telemedicine visits, mailing of investigational product (IP) to the patient’s home, virtual monitor visits, and virtual audits. Practices that were once thought impossible or undesirable were implemented out of necessity. In fact, some of these workflows have become preferred by many due to the conferred efficiencies.

Prior to the pandemic, most IDS pharmacies and trial units hosted their monitoring visits exclusively in person. To reduce exposure to COVID-19 most sites enacted severe visitor restrictions. To balance the regulatory oversight of clinical trials and the risk reduction, clinical trial units and IDS pharmacies sought alternative strategies to fulfill contractual objections. When visitor restrictions were put into place, most sites transitioned to virtual or remote visits. Some sites had already implemented virtual visits prior to 2020, and they served as role models for those of who looked to quickly implement an entirely new workflow overnight. Hosting virtual IDS and regulatory visits provided IDS pharmacies new benefits and challenges. Leveraging technology such as secure meeting platforms, email, telephone, and electronic inventory systems as virtual monitoring locations, staff no longer need spend to their days sitting with their on-site visitors and hosting in-person visits. For those with electronic accountability systems, study documents can be uploaded in secure platforms or provided electronically not only saving time, but immense amounts of paper and physical meeting space. For those managing paper accountability forms and other paper documents in physical binders, it presented the challenge of additional time spent making copies, scanning, and organizing that the monitor would have otherwise done. The benefits of a paperless IDS operations became even more clear given the apparent efficiencies that these remote visits can have. What once seemed to be a temporary process to bridge the gap, now appears to be a strong contender for permanent change in monitoring visit operations at trial sites.

The care and management of clinical trials traditionally has required patients to come on-site for in person visits. During the initial release in March of 2020, the US Food and Drug Administration published guidance for the conduct of clinical trials during the pandemic. Recommendations provided to date state that “alternative methods for safety assessments (e.g., phone contact, virtual visit, alternative location for assessment, including local labs or imaging centers) could be implemented when necessary and feasible.”¹ Accordingly, sponsors and Institutional Review Boards (IRBs) issued permissions for telemedicine visits. This allowed patients who were otherwise scared, hesitant, unwell, or required by local ordinances to stay at home to continue to have access to medical care. Virtual strategies employed for COVID risk reduction increased the frequency and use of telemedicine visits for standard of care and clinical trials in early 2020. An article by Marra and colleagues published in June 2021 found that the use of connected digital products only increased by 1.65% between May 2020 through February 2021. While this increased is much smaller than anecdotally expected, the author concludes that the “options created by regulatory guidance to stimulate telehealth monitoring were not widely incorporated into clinical research.”² Nevertheless, this transition did allow many clinical trial patients to remain enrolled in their clinical trial and continue treatment. Looking at forthcoming protocols, telemedicine visits are included in protocol procedures as alternatives to on-site visits when appropriate. This is a warranted change for many reasons. A model that includes telemedicine visits has the potential to increase accessibility to clinical trials for patients outside the institution’s catchment area, bring the clinical trial to the patient’s home, reduce travel-related costs incurred by the patient, increase diversity of subjects, and increase equity and inclusion of underinsured, underrepresented, and at-risk patient populations. While on-site visits will likely remain the preference to ensure proper oversight and accountability, a hybrid model is likely to remain a viable option when feasible.

To complement the telemedicine visits and assessments, many sponsors provided exceptions to a previous prohibition on shipping IP to the patient at home. Included in this group of sponsors was the National Institute of Health (NIH) and National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis/NCI which temporarily permitted shipment of IP from the site to the patient home during the pandemic. In January of 2022, the NIH/NCI provided notice that “for studies under CTEP IND with oral investigational agents, CTEP will allow the Dispensing Pharmacy to ship oral investigational agents directly to study subjects.” This is a significant change in trial operations and a signal that mailing IP is an acceptable method to manage patients remotely as we move past the pandemic. This change in practice has provided continued access to clinical treatments during the pandemic and will continue to do so as we emerge into a new way of conducting clinical trials.

While the benefits of shipping are clear, there are many challenges associated with shipping IP which may limit the use of telemedicine and mailing of IP in the future. Without patients coming on site for their visits, real-time accountability of patient returned IP is not always feasible. To accomplish this remotely, oral IP accountability will need to occur over a telemedicine visit or through creative methods (e.g. patient submitted photographs, technologically enhanced IP bottle caps that track adherence and doses). Using a phone, camera, or computer may be difficult for patients as they attempt to maneuver their electronic devices close enough for the provider to view an array of capsules or tablets. Formally, IP accountability would need to be done once the IP supplies for the prior cycle(s) are physically at the site. From a site perspective, shipping IP to patients can be time consuming for staff and expensive. Agents with a CTEP IND require the use of a qualified shipper (to maintain protocol required temperatures and conditions) in addition to the cost of shipping the package, which can be costly. There may not always be available funds to cover the shipping costs. Additionally, pharmacy shipment of IND-exempt IP directly to the patient is subject to Board of Pharmacy regulations. Due to the associated licensing and regulatory complications, this often removes the ability to ship this IP interstate and requires the patient to come on site to pick up their outpatient medication(s). Limitations such as these may prevent some sites and patients from taking full advantage of what is otherwise feasible and frequently used dispensing process for standard of care patients. Finally, the additional physical space and labor involved to provide shipping services on a frequent basis cannot be understated. The support of pharmacy departments, health system and research offices must be present to advocate and consider any additional resources that may be needed in the IDS pharmacy.

As we move into the post-pandemic era, the number of clinical trials activated at sites will naturally increase opportunity for enrollment. From February 2020 to May 2020, clinical trial activations “were only 57% of the expected estimate had the pandemic not occurred” as compared with 77% of non-US-based trials.³ While a rebound in activated trials occurred across sites as communities re-opened, many clinical trial sites are still impacted by COVID-related staff shortages and continued restrictions.

If the pandemic serves as nothing else, it has been a catalyst for change. It has provided clinical trial units, IDS pharmacies, clinical trial research organizations (CROs) and sponsors with a new vantage point and a glimpse into what the possibilities are: a research world where the clinical trial meets the patients at their home and increasing efficiencies for those operating the trials through the leverage of technology and modern structure. With eased restrictions and the return to some semblance of pre-pandemic times, healthcare providers, pharmacies, and trial units are faced with the reality of deciding what the future of clinical trials holds. It is up to all stakeholders to evaluate what serves their department, site, patient population, and research community well and to part ways with what does not serve them. Just as the past two years have forced clinical trial units, IDS pharmacies, and supporting departments to operate with the utmost of patient centered focus, the pandemic can also now serve as a reset and a chance to revise and/or reaffirm operations. By embracing these opportunities in the long-term, health care providers, clinical trial units, and IDS pharmacies can improve their efficiencies, improve patient centricity, and practice in line with their values and patient centered models.

REFERENCES

1. Food and Drug Administration. (2021). Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards. https://www.fda.gov/media/136238/download. Accessed 21 JUN 2022.
2. Marra C, Gordon WJ, Stern AD. Use of connected digital products in clinical research following the COVID-19 pandemic: a comprehensive analysis of clinical trials. BMJ Open 2021;11:e047341. doi: 10.1136/ bmjopen-2020-047341.
3. Unger JM, Xiao H. The COVID-19 pandemic and new clinical trial activations. Trials. 2021;22(1):260. Published 2021 Apr 8. doi:10.1186/s13063- 021-05219-3.