 |
|
Registration of Clinical Trials
Arch Ophthalmol. 2005;123:1263-1264.
The gold standard for assessing the efficacy of a therapy is the controlled clinical trial. The Declaration of Helsinki mandates that clinical trials should only be performed with volunteers, and therefore the progress of medicine is absolutely dependent on the immense generosity of subjects willing to be part of a clinical trial. They do this in return for the greater good for society, yet this beneficence is not always returned. We know that many clinical trials are not reported, leading to difficulties in assessing the true efficacy of a therapy. Underreporting of clinical trials also can obscure the adverse effect profile of an intervention, as witnessed by the recent COX-2 inhibitor debacle.
In response, the International Committee of Medical Journal Editors (ICMJE), the World Health Organization, and even national political bodies have endorsed the concept of clinical trial registration. This proposal would require that details of a clinical trial be publicly disclosed before recruitment as a condition for subsequent publication. Most major medicine journals, eg, JAMA, New England Journal of Medicine, and Annals of Internal Medicine now require clinical trial registration. Starting March 1, 2006, the Archives of Ophthalmology, American Journal of Ophthalmology, British Journal of Ophthalmology, and Ophthalmology will require that human clinical trials beginning enrollment on or after that date will have to be registered before enrollment in order for the results to be published in our journals. Trials that already began enrollment before March 1, 2006, will have to be registered by June 1, 2006.
REQUIREMENTS FOR REGISTRATION
Which clinical studies need to be registered? Following the lead of the ICMJE, we will require registration of human clinical research projects that prospectively assign subjects to intervention and concurrent control (comparison) groups in order to study the cause-and-effect relation between a medical intervention and a health outcome.1-2 This would encompass all phase 2 and 3 studies that test the efficacy of an intervention, but not, for example, case reports or small case series, retrospective studies, or any other exploratory clinical studies for which concurrent groups are not prospectively assigned.
HOW IS REGISTRATION PERFORMED?
Registration can be through any registration site that is publicly available, freely and electronically searchable, administered by a nonprofit entity, and for which registration can be performed for free or at a nominal charge. A commonly used registration site is clinicaltrials.gov. Other sites that meet the requirements of the ICMJE1-2 are also acceptable. Registration data include the disease being studied, the intervention, the targeted enrollment size, the outcome measures, and several other items detailed in the World Health Organization April 2005 recommendations and published in a recent JAMA editorial.2 All fields need to be filled with meaningful information for registration to be considered complete.
WHAT IF I DO NOT REGISTER MY CLINICAL TRIAL?
If a manuscript is submitted on a trial that is not registered, then a case will have to be made to the journal editor that the results of the trial are of such public health importance that the failure to register is superseded by the benefit to society. We suspect that this exception will rarely occur, and our expected response is to refuse to review or publish such manuscripts. As time goes on, other ophthalmology journals are expected to join in requiring clinical trial registration, and eventually it may even be mandated by national law.
HOW IS CLINICAL TRIAL REGISTRATION JUSTIFIED?
As stated previously, subjects donate their time and accept risk and in some cases their health for medical research. Yet sometimes a carefully designed and well-performed trial is carried out and yields negative results, but the data are never published or publicly released. In these cases the subject has donated his or her effort for the public good, but all may be for naught because of the failure to publish the results. In cases where there are adverse effects or a lack of efficacy is demonstrated, the failure to publish otherwise useful data has effectively squandered the contribution from the subject. This is ethically wrong, and clinical trial registration is one way of making sure that human subjects research is performed in an ethical manner.
AUTHOR INFORMATION
Corresponding Author: Dr Levin, Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, 600 Highland Ave, Madison, WI 53792.
Leonard A. Levin, MD, PhD;
Justin L. Gottlieb, MD;
Roy W. Beck, MD, PhD;
Daniel M. Albert, MD, MS
Archives of Ophthalmology
Thomas J. Liesegang, MD
American Journal of Ophthalmology
Creig S. Hoyt, MD;
Andrew Dick, FRCS;
Robert Bhisitkul, MD, PhD
British Journal of Ophthalmology
Andrew P. Schachat, MD
Ophthalmology
REFERENCES
1. DeAngelis C, Drazen JM, Frizelle FA, et al, International Committee of Medical Journal Editors. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. JAMA. 2004;292:1363-1364.
FREE FULL TEXT
2. DeAngelis CD, Drazen JM, Frizelle FA, et al, International Committee of Medical Journal Editors. Is this clinical trial fully registered? a statement from the International Committee of Medical Journal Editors. JAMA. 2005;293:2927-2929.
FREE FULL TEXT
RELATED LETTERS
Regarding Registration of Clinical Trials
Anja M. Palmowski-Wolfe
Arch Ophthalmol. 2007;125(6):853.
EXTRACT
| FULL TEXT
Regarding Registration of Clinical Trials—Reply
Leonard A. Levin
Arch Ophthalmol. 2007;125(6):853.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Regarding Registration of Clinical Trials
Palmowski-Wolfe
Arch Ophthalmol 2007;125:853-853.
FULL TEXT
ARVO Statement on Registering Clinical Trials
IOVS 2006;47:1-2.
FULL TEXT
|
