Following a request for information by the White House’s Office of Science and Technology Policy (OSTP), a number of industry groups offered suggestions for priming the U.S. clinical research infrastructure to effectively respond to future public health emergencies.

Pharmaceutical Research and Manufacturers of America (PhRMA), the Association of American Medical Colleges (AAMC), the Council on Governmental Relations (COGR) and others stressed the importance of diversity initiatives, but utilizing decentralized trials (DCT)/digital health technologies (DHT), expanding U.S. research capabilities, and developing emergency master contracts were also recommended.

Diversity Development

PhRMA believes that community involvement and education will be essential to building trust in trials conducted to address public health crises, just as it is for normal clinical research.

“It will be critical to think through a robust education and outreach effort to address potential misperceptions that ‘emergency’ suggests any jeopardizing of a focus on safety and efficacy,” the trade group wrote in its comments.

PhRMA advocated for the development of community-based research sites in underserved areas, highlighting it as a critical component for improving diversity and identifying trust building as a solid starting point. In building up these sites and making trials more accessible to their surrounding populations, the trade group recommended:

• Considering the needs of diverse groups when designing trials;
• Implementing enrollment/retention strategies that improve inclusivity while reducing participation burdens; and
• Expanding eligibility criteria in trials when appropriate.

Education, too, is critical, not just for enhancing diversity of trial populations but for improving inclusion of investigators, trial staff and others involved in running trials, PhRMA wrote.

Reaching out to medical professionals and educating sites on clinical research in underserved communities is particularly pivotal, the group wrote, as is community outreach that improves trial awareness, health education and individual health literacy. In addition, acknowledging past scientific wrongs done to underrepresented groups is important.

The MITRE Center for Data-Driven Policy posed another diversity strategy: reducing trial complexity and costs. Often, simpler trial designs and quality-by-design approaches can help reduce the level of data collection required and, as a result, reduce burden for sites and participants alike, lowering a barrier to diversity by extension, the nonprofit said.

“Experts agree that many trials are too complex and that simpler, streamlined trials would allow us to answer many important clinical questions. This, in turn, will enable us to reach more diverse patients who do not have the time and resources to participate in trials at large academic medical centers,” the group wrote.

Use of DCTs and New Technologies

Wisely using new tools and technologies can also cut down data collection workloads, MITRE advised. For instance, technology can help embed data collection in the electronic health record (EHR) to make data collection less arduous for clinicians while adding to real-world data and directly gathering data from patients.

Similarly, PhRMA voiced its support for using and advancing technology solutions, such as DHTs and DCT methodologies, to enable increased access to trials during health emergencies, pointing to their impact during the COVID pandemic to facilitate participation.

However, while these tools have the potential to provide “scientific and practical advantages,” PhRMA reminded OSTP that patient access to high-speed internet and digital technologies may vary significantly. Similarly, the Milken Institute, a nonprofit think tank, echoed this sentiment.

“Researchers must be careful not to disenfranchise underserved communities through DCTs and remote tools, despite their usefulness,” the institute wrote. Although these methods aim to engage more communities, they may contribute to further barriers for patients who lack the technology required to participate.”

According to MITRE, trial execution experts widely agree that simplifying trials and using new technological solutions also requires cutting the costs of U.S. trials tenfold. If this is achieved, bringing trials outside of academic centers and into the community will be made easier, MITRE advised.

As diversity initiatives continue, MITRE also recommended clearly assessing, tracking and cutting per-patient costs, which it claims now exceed $40,000 per patient on average, noting that these current costs and accompanying resources would be hard to sustain through a pandemic.

‘Warm Base’ Research

Stakeholders also support establishing a “warm base” of research, an approach meant to bolster U.S. trial capacity by training trial-inexperienced sites on regulations, procedures and data-gathering ahead of the mass launch of a protocol(s) to address a public health emergency.

AAMC implored OSTP to consider this “sorely needed and resource intensive” initiative and determine how it could be initiated and funded at sites with little bandwidth for research, but warned “even simple data collection trials created to build this capacity through ‘warm base’ research must themselves be ethically and scientifically sound and conducted and overseen by trained research staff.”

MITRE also signaled support for warm base research and recommended a focus on:

• Disease areas with high health burden and unmet medical need, particularly in underserved and vulnerable communities;
• Communities with specific research questions that could meaningfully benefit if these questions were answered;
• Research with little commercial incentive; and
• Questions that can be answered by point-of-care trials.

Emergency Trial Master Agreements

Though stakeholders expressed some skepticism over use of trial master agreements — trial agreements easily acceptable to all sites and sponsors that eliminate back-and-forth negotiations and save significant time/resources — they did offer some recommendations.

COGR, which described master agreements as a longtime “Holy Grail” of clinical trials, noted the challenges inherent in developing them but also heralded prior successes in creating less comprehensive contract templates that could be useful in an emergency situation. In particular, the research association noted that non-U.S. entities may throw collaborative complexities into the mix.

“Global and political circumstances may make research institutions of all types reluctant to work with certain international partners, yet their information, data and expertise may be essential to addressing the emergency. OSTP and U.S. government agencies must be prepared to provide clear direction on any prohibited collaborations,” COGR advised.

Pathways for rapid intergovernmental communication and measures to enable global emergency research, such as international regulatory flexibilities, will be critical as well, the council added.

Because of the array of organizations that may be involved in emergency trials, the contract provisions, terms and capacity assessments required may differ between trials and organizations, AAMC noted, with interventional trials, observational trials and reviews of medical records all requiring different expertise and infrastructure.

Due to this, “a tiered set of agreement provisions allowing each institution to opt in to a threshold set of terms based on its current [trial] capacity” should be considered, the association said.

Further, AAMC cautioned that many institutions could be barred contractually from starting or taking part in other trials upon signing a master agreement. “Without knowing in advance what the agreed-upon trials would seek to answer, this might have a chilling effect on the willingness of some organizations to participate,” the association warned.

Read AAMC’s comments here: https://bit.ly/42yzn9L.

Read COGR’s comments here: https://bit.ly/3TDul8b.

Read the Milken Institute comments here: https://bit.ly/3yY8YVp.

Read MITRE’s comments here: https://bit.ly/40jCOPU.

Read PhRMA’s comments here: https://bit.ly/3z5luTi.