Historically, drugs studied in clinical trials are dispensed to participants by pharmacies located at investigating sites — e.g., academic medical centers and hospitals.
Both sponsors and patients are keen, however, to deploy “decentralized” or “remote” approaches when reasonably possible — for example, having routine procedures like a blood draw, injection/infusion or physical status evaluation (vital signs, EKG) performed by local practitioners or itinerant providers. Traceable shipping and widespread communication technology facilitate decentralized (or at least hybrid) study activities. Wearable devices also can be used to collect information on an ongoing basis and in circumstances reflecting real-world life.
Ease of study participation (less travel, less time away from work, school and family, etc.) can significantly improve patient recruitment and retention (both major challenges). Participation may become newly available to individuals who could not join previously (too far away from a study site; unable to take off work for an extended time). Broader geographic reach may enhance studies involving rare diseases. An additional, important benefit may be to reach more diverse populations — good toward health equity generally and scientifically important to ensure the generalizability of clinical research results. Finally, decreased operational costs are always a driver for sponsors selecting flexible, least burdensome operations.
The COVID-19 pandemic forced a hard look at decentralized clinical trials. Impossibility for trial participants to enter investigating sites due to pandemic restrictions, lack of availability of investigators due to heavy health care duties, increased acceptability of telehealth interactions, and other consequences of the pandemic led authorities around the world to accept thoughtful flexibility in the application of clinical trial rules in order to ensure continuity of then-ongoing clinical trials.
This regulatory flexibility brought decentralized clinical trials closer to 21st century reality. Now, while the COVID-19 crisis is no longer acute, pharmaceutical companies and other sponsors want to continue benefiting from flexibility that proved quite valuable and desirable.
The supply of study drugs and, more generally, clinical supplies through channels other than institutional pharmacies was among customary trial features that the authorities had to let go. As a general rule, during the COVID pandemic, clinical supplies could be delivered to trial participants either directly or through investigators, the latter a generally less efficient solution.
Direct delivery to patients is a seductive proposition for sponsors. Seductive but also complex, because they must provide trial participants with the same guarantees as if the trial was conducted at the hospital. Transportation, delivery and storage of clinical supplies has become more challenging to organize, especially as the geographical reach of trials expands. Test article administration and subsequent collection of study materials also require attention.
As the concept of decentralized clinical trials moves forward, reliance on community pharmacies as suppliers of clinical supplies and related services may be the right compromise between the protection of trial participants and supporting secure trial participation.
Regulatory guidance under active development
Discussions concerning “decentralized” clinical trials are alive as never before. The Food and Drug Administration’s Center for Drug Evaluation and Research has announced its plan to publish regulatory guidance during 2022. The agency’s Oncology Center of Excellence has requested information allowing it to compare remote versus trial-site assessments that occurred during COVID, thereby evaluating opportunities and challenges to foster the use of decentralized clinical trials prospectively.
Similarly, in Europe, the European Medicines Agency (EMA) will hold a workshop on decentralized clinical trials on October 4. The “ACT EU Programme” will host a multi-stakeholder workshop bringing together participants from all areas of the research community to share perspectives on this type of clinical trials. A live broadcast of the workshop’s plenary session will be open to all interested parties; the EU project group will present the work of the European Medicines Regulatory Network on decentralized clinical trials (DCT) collaboration, including the planned publication of a guidance paper in the fourth quarter of 2022. The workshop will include breakout sessions with an opportunity for discussion on topics of relevance to decentralized clinical trials, facilitated by the core members of the EU DCT project team (clinical trial experts from the Clinical Trials Coordination Group (CTCG), ethical experts from the Commission Expert Group on Clinical Trials (CTEG) and Good Clinical Practice (GCP) inspectors from the Good Clinical Practice Inspectors Working Group (GCP IWG). The workshop aims to bring forward, among other topics, the perspective of patient representatives and investigator site experts.
Role of community pharmacies in research
Community pharmacies provide similar services, subject to the same rights and ethical duties, as institutional pharmacies. Yet community pharmacies are geographically closer to patients and thus easier to access. In addition, community pharmacies have a trusted role in the community, rendering them potentially attractive to drug sponsors as familiar and welcoming participants in the clinical trial enterprise.
Many community pharmacies belong to large companies or networks that facilitate logistics and may justify by scale the development of procedures, training and stringent delineations that would be necessary to distinguish clinical research operations from practice of pharmacy. More and more community pharmacies also have an adjunct health care operation (clinic) that can perform complex drug administration or other procedures that are customary in clinical trials. Chains of community pharmacies/mini-health care centers offer national capable partners to sponsors.
There are many requirements for Good Clinical Practice (GCP) and other legal compliance with regard to clinical research. Considerations include: scope of practice definitions, obligations for segregation of products and files, meticulous accountability, application of privacy protections, sometimes unclear rules overlapping from pharmacy law, etc. Sponsor oversight and regulatory inspections also must be anticipated, and necessitate considerations of training, access to facilities and computer systems, etc.
Participation in clinical research is rewarding and can be lucrative. But it is not for the faint of heart, and would require careful scrutiny of rewards, risks and obligations.
Geneviève Michaux (Brussels) and Christina Markus (Washington, D.C.) are attorneys at King & Spalding.