Advancing the Quality of Clinical Trial Enterprise
Focus Area: Current Project
Focus Area: Ethics, Conduct, and Oversight
Clinical trials are a critical component of the medical evidence base. Evidence that substantial numbers of trials do not contribute meaningful information to the evidence base raises both ethical and scientific concerns. Participants assume the risks and burdens of a study, while mistakenly believing that they are contributing to medical progress. At the same time, these non-informative trials divert participants, researchers, and other resources from more valuable trials, potentially making it more difficult to reach enrollment targets.
Examples of trials of concern include not only those conducted long after the study question has been answered by previous studies but also those trials that fail to complete. In addition, there are large numbers of trials that are not incorporated into systematic reviews because of lack of relevance (e.g., use of inappropriate comparators) or high risk of bias (e.g., due to flaws in randomization process). Requirements for trial registration and results reporting have greatly improved the availability of information about ongoing and completed trials, while simultaneously exposing the issues with incomplete and poor reporting of results.
Although others have identified the conduct of non-informative trials as a significant problem, there has been less progress in defining, studying, and attempting to reduce their frequency and thus improve the quality of the medical evidence base. We intend to take on this challenge. In addition, we intend to build on the established foundation of trial reporting to ClinicalTrials.gov with the aims of improving the timeliness and quality of reports, as well as increasing the use of data from ClinicalTrials.gov by the research enterprise.
The COVID-19 pandemic is providing a real-time laboratory for studying how inefficiencies in the research enterprise could be addressed. Examples of problems that we are focusing on include lack of harmonization of trial designs for various therapeutics; lack of sufficient reporting for evaluations of diagnostic tests; and delayed reporting of summary results leading to the promulgation of policies based on incomplete data.
Current Status: Active
Improving the design and the quality of clinical trial reporting will result in a reduction in the number of non-informative trials that are initiated. Along with improved trial reporting, the impact will be a higher quality clinical trial evidence base and ultimately the improved use of clinical trial data to inform research decisions. These issues are especially urgent during the current COVID-19 pandemic.
We will conduct a suite of activities aimed at addressing three problems affecting trials conducted at US academic medical centers (AMCs):
- poorly designed clinical trials
- poorly reported clinical trials
- insufficient use of trial data to inform research decisions, such as the initiation of new trials
Currently, the following projects are in varying stages of development:
- Developing “best practices” for the conduct of landscape analyses that enable researchers and other oversight entities to understand what is already known, and what is currently being investigated, about their research question
- Analyzing large samples of informed consent forms in order to establish better (and worse) practices, and to start to develop tools that might help researchers to write future consent forms
- Increasing use of data from ClinicalTrials.gov to inform research decisions
- January 2020: Published article about issues in the registration of database studies
- March 2020: Published article “Time for NIH to lead on data sharing”
- April 2020: Published white paper on considering false positive and false negative results in testing for COVID-19
- December 2020: Published letter to the editor on lack of harmonization of coronavirus disease ordinal scales
- January 2021: Contributed to article on complete, rapid reporting of clinical trials
- April 2021: Served on NASEM committee which released a report on genomic epidemiology data infrastructure; published article about lack of harmonization of COVID ordinal scales
- May 2021: Published article about Trial Reporting and the Clinical Trials Enterprise
- October 2021: Published article about Monitoring the Pediatric Clinical Trials Enterprise
- November 2021: Published article about Characterization of Informed Consent Forms posted on ClinicalTrials.gov
- Deborah Zarin, MD, Program Director, Advancing the Clinical Trial Enterprise, MRCT Center
- Barbara E. Bierer, MD, Faculty Director, MRCT Center
- Sarah White, MPH, Executive Director, MRCT Center
Contact information: email@example.com