In 1974, Mary Lasker, advocate and patron of clinical research, requested the National Cancer Institute publish a book listing all ongoing cancer treatment protocols in the United States.1 The book would be updated every 6 months, its purpose being to provide physicians with information on open trials in which they could enroll their patients. A few years later, Tom Chalmers, former National Institutes of Health director and dean at Mt. Sinai Medical Center, expanded the concept to include clinical trial registers for all areas of medicine.2 Both Lasker and Chalmers recognized a gap in the dissemination of good information; both hoped to speed the delivery of the best new treatments to the patient.3
Beginning in July of 2007, Plastic and Reconstructive Surgery will require all articles reporting results of clinical trials to be registered in a public trials registry. Registration of clinical trials has become a standard requirement for many major biomedical journals over the last few years. What follows is information on registering clinical trials that every plastic surgeon needs to know.
WHAT IS A CLINICAL TRIAL? WHAT IS A TRIAL REGISTER?
The International Committee of Medical Journal Editors defines “clinical trial” as any research project that prospectively assigns human subjects to intervention and concurrent comparison/control groups to study the cause-and-effect relationship between a medical intervention and a health outcome. Medical interventions include any intervention used to modify a health outcome. This definition includes drugs, surgical procedures, devices, behavioral treatments, process-of-care changes, and the like. Studies designed for other purposes, such as to study pharmacokinetics or major toxicity (e.g., phase I trials), would be exempt.4 Clinical trials strive to provide information regarding the safety and effectiveness of biomedical or behavioral interventions; they can include the use of drugs, devices, treatments, or new ways of using existing treatments.5 There are four subtypes of clinical trials, as described below:
Phase I: Determines the safety of protocols, usually with a small number of normal patients
Phase II: Defines effective protocols in patients (usually n > 100) (therapeutic exploratory trials)
Phase III: Compares the new treatment with other standard treatments in a larger group of patients (usually n > 1000) (therapeutic confirmatory trials)
Phase IV: Monitors effectiveness and adverse events in the general population after marketing clearance is granted (therapeutic use trials)
Publication of large-scale clinical trials data is common with pharmaceuticals and certain surgical procedures, such as common cardiac and orthopedic interventions. Smaller trials are more common in the literature for smaller specialties, such as plastic surgery. Regardless of the size of the clinical trial, however, registration in a national trial registry will become a standard procedure for clinical investigators.
A trial registry is a database (nearly all are Web based) that serves as a repository for basic information regarding clinical trials. Trial registries include the following information6:
- Trial title
- Research question
- Study population and list of interventions
- List of investigators and their institution(s)
- Source of funding
- Unique identifier to preclude repeat investigations
- Status of trial (ongoing or completed, open or closed)
- Methodology of trial
- Ethical aspects, including type of consent, information given to participants, and institutional review board approval
- Results, whether they have been published or presented
- Full protocol
The inclusion of such data promotes (even demands) hypothesis-driven, evidence-based research utilizing sound methodology. Registering clinical trials will, over time, improve the quality of research, patient safety, and efficacy of treatment. These benefits will potentially enhance the safety, quality of care, and outcomes for our patients in reconstructive and cosmetic surgery.
IMPORTANCE OF REGISTERING TRIALS: ADDITIONAL BENEFITS
Registering a clinical trial means putting on public record some basic information about the trial from its inception.6 The aim is to provide reliable information about research in progress to the public, health providers, researchers, and funding agencies. There are multiple reasons for doing so,6 including the following:
- To lessen publication bias (the underreporting of trials with negative, disappointing, or inconclusive results), which misleads researchers conducting systematic reviews and doctors making treatment decisions based only on published evidence
- To prevent unnecessary duplication of research effort
- To encourage appropriate replication and confirmation of results
- To alert researchers to gaps in the knowledge base
- To foster collaboration among researchers
- To encourage recruitment to trials
- To provide reliable data about ongoing trials in order to help funding agencies provide money where it is most needed
- To provide unbiased evidence on the efficacy of treatments to the public
- To promote overall accountability of medical research in general
Registered trials contribute to the evidence pool for healthcare decisions, whereas unregistered trials do not. Patients, researchers, governments, publishers, and funding agencies alike agree that clinical trials should be registered in the interests of evidence-based medicine and freedom of information.
Plastic and Reconstructive Surgery AND REGISTERING TRIALS: NEW GUIDELINES
Beginning in July of 2007, Plastic and Reconstructive Surgery will require, as a condition of consideration for publication, registration of all trials in a public trials registry that is in conformity with the International Committee of Medical Journal Editors (ICMJE) and that requires the minimum registration dataset as described by this committee (http://www.icmje.org/faq.pdf). The member journals of the Surgery Journal Editors Group (SJEG) (including Plastic and Reconstructive Surgery) have agreed to adopt the position of the ICMJE regarding mandatory registration of publicly funded clinical trials as a condition of consideration for publication. All clinical trials, regardless of when they were completed, and secondary analyses of original clinical trials must be registered before submission of a manuscript based on the trial. For clinical trials that start patient enrollment after July 1, 2007, trials must be registered before the onset of enrollment. Phase I trials designed to study pharmacokinetics or major toxicity are exempt. The SJEG member journals (including Plastic and Reconstructive Surgery) will require registration of all prospective clinical trials, including commercially sponsored phase I and II trials, as of July 1, 2007. Trials that begin after July 1, 2007, must register before enrollment of the first study subject, and trials that begin before the deadline must register prior to editorial review.
Manuscripts reporting on clinical trials (as defined above) should indicate that the trial is registered and include the registry information on a separate page, immediately following the authors’ financial disclosure information.Required registry information includes trial registry name, registration identification number, and the URL for the registry.
Trials should be registered in one of the following trial registries:
- http://www.clinicaltrials.gov/ (Clinical Trials)
- http://actr.org.au (Australian Clinical Trials Registry)
- http://isrctn.org (International Standard Randomized Controlled Trial Number, or ISRCTN, Register)
- http://www.trialregister.nl/trialreg/index.asp (Netherlands Trial Register)
- http://www.umin.ac.jp/ctr (UMIN Clinical Trials Registry)
The above information is now included in the Journal’s Information for Authors, which is printed in the Journal and is also available on the Journal Web site (www.PRSJournal.com) and on the Enkwell Web site (www.editorialmanager.com/prs).
HOW TO REGISTER A TRIAL
To register a trial, follow the directions provided by the trial registry. We recommend the following registry: www.clinicaltrials.gov. As an example, to register a trial with this registry, take the following steps7:
- Visit the Web site (www.clinicaltrials.gov).
- Log in with the following information:
From the Main Menu screen, select “Create.”
Enter your grant number and the Unique Protocol ID.
Enter a brief (lay) title and select “Continue.”
Provide as much information as possible in the available fields. Complete all of the 20-item minimal dataset. Include both a brief summary and a detailed description. List both inclusion and exclusion criteria in the “Eligibility” criteria field.
When you have completed the record, select “Next Action: Complete.”
- a) Organization (that has funded the trial);
- b) User Name: your name; and
- c) Password: your choice.
The article by Jonasson7 provides an example of a completed registration form.
We are convinced that the registration of clinical trials for papers submitted to Plastic and Reconstructive Surgery will not only have an overall positive effect on patient safety and the quality of healthcare but also elevate the quality of research and clinical science published in the Journal. We look forward to the benefits such registration will have in raising the quality of articles sent to the Journal.
1. Hubbard, S., and DeVita, V. T. PDQ: An innovation in information dissemination linking cancer research and clinical practice. In V. T. DeVita, S. Hellman, and S. A. Rosenberg (Eds.), Important Advances in Oncology.
Philadelphia: Lippincott, 1987.
2. Chalmers, T. C. Randomize the first patient! N. Engl. J. Med.
296: 107, 1977.
3. Dickersin, K., and Rennie, R. Registering clinical trials. J.A.M.A.
290: 516, 2003.
4. International Committee of Medical Journal Editors. Frequently asked questions about clinical trials registration. Available at www.icmje.org/faq.pdf
. Accessed August 22, 2006.
5. Merrick, M. A. New requirements for registering clinical trials. J. Athl. Train.
40: 8, 2005.
6. Tonks, A. Registering clinical trials. BMJ
319: 1565, 1999.
7. Jonasson, O. The importance of registering clinical trials. J. Am. Coll. Surg.
202: A30, 2006.