Abstract
Background: Clinical research that is incomplete and unreported can lead to bias in health care decisions. Selective reporting of outcomes in clinical research overestimates the benefits and safety of treatments and threatens the integrity of systematic reviews of health care interventions. The Common Rule does not require that results be made available from clinical studies to research subjects and the scientific community. Methods: We analyzed all closed studies (i.e., no longer recruiting) registered in the online database ClinicalTrials.gov as of May 2010 to identify the number, length, and characteristics of complete and incomplete (terminated, suspended, or withdrawn) studies. Random samples of terminated studies, which were defined as studies in which the recruitment or enrollment of participants has been halted prematurely and will not resume, were analyzed to identify the reasons for termination and availability of the results in ClinicalTrials.gov or in published articles. Results: We identified 3,554 (6.2%) terminated studies among 57,233 closed studies. Reasons for termination were unknown in 34% and safety-related in 11% of terminated studies. Industry-funded studies omitted termination reasons less often than National Institutes of Health (NIH)-funded studies (OR 0.3, 95%CI: 0.1, 0.9). Drug studies omitted termination reasons more often than all other intervention studies. (OR 2; 95% CI: 1.1, 3.7) and also cited safety as the termination reason (OR 8.6; 95%CI: 1.9, 36.8) more often than other intervention studies. Terminated studies lasted on average 2.2 ± 1.9 years, and results were available for 5% in ClinicalTrials.gov and for 8% in peer-reviewed journals. Conclusions: Existing clinical research policies should mandate registration of all clinical trials in ClinicalTrials.gov as a condition of studies approval by institutional review boards. Mandatory posting of the results in ClinicalTrials.gov for all terminated studies, along with the exact reasons for termination irrespective of study funding and market or publication status, would enhance comprehensive evidence analysis by clinicians and policymakers, as well as public trust in clinical research.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-18 |
| Number of pages | 18 |
| Journal | AJOB Primary Research |
| Volume | 3 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 2012 |
Bibliographical note
Funding Information:Adding downloadable field in the Research Portfolio Online Reporting Tools (RePORT) grant database with a registration status and registration identification number for all clinical trials funded by the NIH Participants are informed about posted protocols and plans to post the results from clinical trials.
Funding Information:
Informing the NIH funding agencies (automated e-mails) about absent or incomplete posting of the results from the NIH funded trials
Funding Information:
nih.gov/reporter.cfm) contains complete information about all grants funded by the NIH, but does not have variables indicating study registration or recruitment status. We focused on one registry without examining the studies available in the World Health Organization search portal, which does not allow for searching by termination status or downloading all available field options (available at http://apps.who.int/trialsearch/). Our preliminary search of this portal with the keyword “terminated” retrieved only 90 records. Review of thousands of individual study records was not feasible. We did not analyze posting of the results by whether the trials were conducted within or outside of the United States. With an annual decline of 3.5% in United States-based investigators since 2001(English et al. 2010), many trials seeking marketing approval in the United States may avoid posting of the results because the FDAAA requirements apply only to the U.S. trials (Department of Health and Human Services 1990b; Food and Drug Administration Amendments Act of 2007 2007). Future research should address posting of the results by applicable trials conducted outside the United States.
Keywords
- National Institutes of Health (U.S.)
- National Library of Medicine (U.S.)
- clinical trials as topic
- publishing
- registries
- research peer review
- research support as topic