Registration of Clinical Trials
Guest Editorial by Andrew P. Schachat, MD
A contemporaneous comparison group is required to provide clinicians knowledge of whether a management approach or treatment option is effective, unless the untreated natural history of the disease is very predictable. I hope it is no surprise to anyone reading my comments that we obtain the best efficacy data from randomized controlled clinical trials. Clinical trials are hard to plan, difficult to conduct, usually are very expensive, and typically rely on the cooperation and collaboration of large numbers of researchers. Of course, society also owes a debt and a thank you to the study participants. Much is invested in these trials, and the data that derives from them is precious.
for Clinical Trial Registration
This information is taken from the Table �Minimal Registration Data Set� which can be accessed on the International Committee of Medical Journal Editors Web site at:
� Unique trial number
Comment: The unique trial number will be established by the primary registering entity (the registry).
� Trial registration date
Comment: The date of registration will be established by the primary registering entity.
� Secondary IDs
Comment: May be assigned by sponsors or other interested parties (there may be none).
� Funding source
Comment: Name of the organization(s) that provided funding for the study.
� Primary sponsor
Comment: The main entity responsible for performing the research.
� Secondary sponsor (if any)
Comment: The secondary entities, if any, responsible for performing the research.
� Responsible contact person
Comment: Public contact person for the trial, for patients interested in participating.
� Research contact person
Comment: Person to contact for scientific inquiries about the trial.
� Title of the study
Comment: Brief title chosen by the research group (can be omitted if the researchers wish).
� Official scientific title of the study
Comment: This title must include the name of the intervention, the condition being studied, and the outcome (eg, The International Study of Digoxin and Death from Congestive Heart Failure).
� Research ethics review
Comment: Has the study at the time of registration received appropriate ethics committee approval (yes/no)? (It is assumed that all registered trials will be approved by an ethics board before commencing).
� Condition being studied
Comment: The medical condition being studied (eg, asthma, myocardial infarction, depression).
� Intervention methods
Comment: A description of the study and comparison/control intervention(s) (For a drug or other product registered for public sale anywhere in the world, this is the generic name; for an unregistered drug, the generic name or company serial number is acceptable). The duration of the intervention(s) must be specified.
� Key inclusion and exclusion criteria
Comment: Key patient characteristics that determine eligibility for participation in the study.
� Study type
Comment: Database should provide drop-down lists for selection. This would include choices for randomized vs non-randomized, type of masking (eg, double-blind, single-blind), type of controls (eg, placebo, active), and group assignment, (eg, parallel, crossover, factorial).
� Anticipated trial start date
Comment: Estimated enrollment date of the first participant.
� Target sample size
Comment: The total number of subjects the investigators plan to enroll before closing the trial to new participants.
� Recruitment status
Comment: Is this information available (yes/no)? (If yes, link to information).
� Primary outcome
Comment: The primary outcome that the study was designed to evaluate Description should include the time at which the outcome is measured (eg, blood pressure at
� Key secondary outcomes
Comment: The secondary outcomes specified in the protocol. Description should include time of measurement (eg, creatinine clearance at 6 months).
�Positive� clinical trials, which show that treatment A is better than B, are very useful. Assuming treatment A has better efficacy and comparable safety, clinicians and patients generally will select treatment A unless it is very expensive or inconvenient. We all like the comfort of knowing which treatment is superior. However, there is also value in equivalence, having confidence that A equals B. Treatment A may be much simpler for patients, or less expensive, and if we know it is as good as treatment B, we will recommend it.
�Negative� studies are valuable as well. Treatment with new high-tech treatment C which allows, for example, �small-incision surgery with rapid recovery� may sound great compared to standard approach D, but if there are data from a well-conducted large randomized trial showing that new treatment C in fact does not achieve comparable or better outcomes than old fashioned (and perhaps less expensive) treatment D, we would not recommend the new treatment. The study result was �negative.� If the study is published, we can all learn about the outcomes of treatment C.
Transparency � Key for Ethical Reporting
Sponsors have usually invested a good deal of time, effort, and money developing drug or device or treatment C to get it to the point of human clinical trials. The sponsor of the study with the negative result may choose not to publish the findings. Perhaps they are raising money for other studies and release of a negative result may hinder their ability to raise funds. If a sponsor controls the release of study data, there is a potential conflict of interest. Society usually has an interest in seeing the data and having it released whereas the sponsor may not. The ethical arguments are complex but when research is performed on humans, most medical professionals support transparency and public reporting. I will not list detailed pro and con arguments for release of study data, but if a trial is performed and nothing is ever reported, many of us assume that the outcomes were not wonderful, and if only positive studies are reported, bias seeps into the literature.
The journal I edit, Ophthalmology, supports the registration of clinical trials. When a trial is registered, there is a public announcement that the study exists with a synopsis of the study design and other important information. To encourage registration, many journals, ours included, will not accept manuscripts from trials that have not been registered. It is possible that a private author may forget about this requirement, and even faintly possible that a large sponsor, for example, a drug company, could forget to do this. Since the data may have public health importance, I may make an exception to the policy on a
case-by-case basis, but I hope this will not be necessary. Registration has little or no cost and is quick and easy. Disclosure that the trial is being conducted can be accomplished a number of ways, for example, at the
Andrew P. Schachat, MD, is vice chair for
Clinical Affairs at the Cole Eye Institute, Cleveland Clinic, in Ohio and is the
editor of "Ophthalmology". Dr. Schachat in the last year has been a consultant
for Eli Lilly, OSI/Eyetech, and Neovista.
Retinal Physician, Issue: July 2006