The cost and duration of clinical trials have escalated dramatically in the past 20 years, hampering introduction of new therapies and limiting people's access to high-quality clinical research. Although some clinical trial sites in the United States are efficient in launching new trials and in identifying participants, many suffer from delays in contracting and IRB approvals, and struggle to meet enrollment targets. A lack of access to clinical trials remains a challenge for frontline clinicians and people living with disease. One problem is that the process for initiating a clinical trial site is complex and involves multiple qualifications. Sponsors tend to use the same sites repeatedly – a practice that offers operational and strategic advantages at the expense of generalizability and the inclusion of underserved communities. Local, regional, national, and international regulations add additional hurdles when it comes to streamlining, sunsetting, or harmonizing site qualifications across regions and studies. The consequences are borne by the National Institutes of Health (NIH), foundations, and industry alike, with the ultimate impact on the public.

For over a decade, the Forum on Drug Discovery, Development, and Translation (the Forum) of the National Academies of Sciences, Engineering, and Medicine (National Academies) has devoted time and attention towards addressing the challenges and opportunities for improving the U.S. national clinical trials enterprise. The Clinical Trial Site Standards Harmonization Action Collaborative (the collaborative) was an ad-hoc activity associated with the Forum, which serves as a neutral venue for stakeholders to work together to accelerate progress towards the improvement of our national clinical trials infrastructure.

Objectives

With the participation of stakeholders involved in clinical trials, this collaborative aimed to:

1. Publish a discussion paper that summarizes perspectives on the concept of clinical trial site accreditation and lays out a framework and principles for developing site standards.
2. Undertake an activity to collect, analyze and assess how a core set of trial site qualifications could be harmonized across research sponsors:
   • Compile and categorize clinical trial site qualifications (e.g., site selection and monitoring checklists) from a small group of research sponsors.
   • Analyze and assess clinical trial site qualifications and develop a core set of clinical trial site qualifications that could be considered for broad application by research sponsors.
   • Prepare an discussion document summarizing the results of this activity.
3. Socialize the site standards among key stakeholders to seek buy in and publish the results of this work in a peer-reviewed journal.

Collaborative Activities

The collaborative brought together a group of diverse stakeholders for a series of meetings to develop a framework for harmonizing clinical trial site best practices and consider the potential value proposition for a voluntary accreditation system. A few collaborative participants authored a National Academy of Medicine (NAM) Discussion Paper, It’s Time to Harmonize Clinical Trial Site Standards, in which they summarized their perspectives on the concept of clinical trial site accreditation as well as a framework and principles for harmonizing site standards. Collaborative co-chairs, Clay Johnston (University of Texas, Austin) and Freda Lewis-Hall (Pfizer Inc.) and Forum member Chris Austin (NCATS/NIH) released a New England Journal of Medicine Perspective making the case for a voluntary accreditation system for clinical trial sites.

Starting in 2017, collaborative participants commissioned an analysis by MMS Holdings, a global clinical research organization, to identify similarities, differences, and gaps across the 217 trial site qualifications and compare these qualifications against those laid out in the International Council for Harmonisation Good Clinical Practice (ICH GCP) guidelines. In 2018, a small working group consisting of clinical trial experts, including representatives from government, academic health and research systems, pharmaceutical companies, and contract research organizations undertook an activity to analyze clinical trial site qualifications currently used by research sponsors (e.g., site selection and monitoring checklists) and develop a core set of harmonized site qualifications that could be considered for broad application by research sponsors.

The results of this work were published as a framework for assessing clinical trial site readiness the Journal of Clinical Translational Science along with a series of perspective pieces, which lay out considerations for Clinical and Translational Science Awards (CTSA) hubs, decentralized trials, and implications for achieving more representative clinical trials..

The collaborative, which sunsetted February 2024, was an ad hoc activity associated with the National Academies Forum on Drug Discovery, Development, and Translation. The work of the collaborative does not necessarily represent the views of any one organization, the Forum, or the National Academies and is not subjected to the review procedures of, nor is it a report or product of, the National Academies.