Clinical trials: the case for registration.

A clinical trial is any research project that assigns human subjects prospectively to comparison groups and compares the relationships between a medical intervention and a health outcome. The CONSORT (Consolidated Standards of Reporting Trials) guidelines were established to assist investigators in achieving high-quality research design and reporting (1) but, unfortunately, many clinical trials remain unpublished. Some researchers fail to publish because of negative or inconclusive outcomes; other investigators have given up control, and a funding organization has refused publication. Failure to disseminate clinical trial information (regardless of outcome) has caused considerable concern within the scientific community, particularly among editors of medical journals. (2)

This problem is both ethical and practical. By definition, clinical trials involve patient volunteers. In many cases, patients have accepted considerable inconvenience, discomfort, and risk in choosing to participate in clinical studies. Often, they are aware that they will receive no personal benefit from the study, but they have volunteered to assist medical science in helping future patients. Clinical trial volunteers have a right to know the outcomes of the studies in which they have participated. In addition, we should be able to assure them that physicians will have access to whatever information the study has generated, regardless of its conclusions.

The International Committee of Medical Journal Editors has issued a statement including the opinion that every clinical trial has to be registered in a complete public database in order for an article about that trial to be accepted for review by a medical journal. (2) I believe this opinion is correct and should be endorsed by all medical journals.

Trial registries are readily accessible on the Internet. (3) For example, the Web site ClinicalTrials.gov makes such information available for both physicians and patients. Registration of Phase I trials (pharmacokinetics or drug toxicity) and Phase II (dosing) trials is recommended, but Phase III trial registration should be mandatory. Phase III trials are designed to help determine clinical practice. Evidence from every such project is potentially valuable. Even equivocal or negative results provide the scientific community with important information about what not to do, as well as what not to spend time or money researching again (at least using the same experimental design).

Registering a clinical trial on the ClinicalTrials.gov Web site is easy. Investigators must first apply for a Protocol Registration System (PRS) account. There are two types: organization and individual PRS accounts. Organization accounts generally have multiple users and are used to register all the trials being conducted at an organization; apply at http://prsinfo. clinicaltrials.gov/gettingOrgAccount.html. Individual accounts are used to register trials conducted by a single investigator; apply at http://prsinfo.clinicaltrials.gov/ gettingIndivAccount.html. Within two business days, ClinicalTrials.gov will create the account and send an e-mail with instructions on how to log in to the PRS, so that you can register your trials.

Ethical conduct of clinical research does not end with Institutional Review Board approval and entry of patients; investigators have an obligation to their subjects and the medical community to disseminate study findings. Registration should be expected for all clinical studies that started enrolling patients after September 2005, and registration should be required before such studies are reviewed for publication.

References

(1.) The CONSORT statement: Revised recommendations for improving the quality of reports of parallel-group randomized trials, http://www. consort-statement.org/Statement/revisedstatement.htm.

(2.) DeAngelis CD, Drazen JM, Frizelle FA, et al. Clinical trial registration: A statement from the International Committee of Medical Journal Editors [editorial]. JAMA 2004;292:1363-4.

(3.) Haug C, Gotzsche PC, Schroeder TV. Registries and registration of clinical trials [editorial]. N Engl J Med 2005;353:2811-12.

ROBERT THAYER SATALOFF, MD, DMA 

Editor-in-Chief

EAR, NOSE & THROAT JOURNAL