 |
|
Publication of Clinical Trials in JAMAInformation for Authors
Phil B. Fontanarosa, MD, MBA;
Catherine D. DeAngelis, MD, MPH
JAMA. 2008;299(1):95-96.
Fulfilling the key objective of JAMA, "To promote the science and art of medicine and the betterment of the public health,"1 involves publishing the most important biomedical investigations and clinical research articles possible. Rigorously conducted randomized clinical trials (RCTs) provide the highest level of scientific evidence for interventions and treatment to enable physicians and other practitioners to provide better care for patients and ultimately to improve the health of the public. Therefore, publication of high-quality, major RCTs represents a top priority for JAMA.
JAMA has published a substantial number of major RCTs, including landmark trials that were immediately practice changing2-3; major clinical trials with important practical application and implications4-5; and innovative, cutting-edge trials that have advanced biomedical research.6-7 Although observational studies and systematic reviews also are extremely important and valuable sources of scientific and clinical information, RCTs will continue to receive the highest consideration for publication.
For authors of RCTs, JAMA offers the advantages of large circulation (print circulation of more than 350 000), extensive reach (approximately 2 million Web site page views per week), high impact factor (23.2), and short time to publication (median of 81 days from submission to acceptance, and 37 days from acceptance to publication). The Instructions for Authors8 published in this issue of JAMA includes detailed information about manuscript preparation and submission. Many aspects of these instructions are specific for clinical trials and should be helpful for authors preparing manuscripts reporting results of RCTs. Several important features related to RCTs deserve emphasis.
First, as a condition of consideration for publication, JAMA requires that all RCTs must be registered in a public trials registry that is acceptable to the International Committee of Medical Journal Editors (ICMJE)9-10 and that requires the minimum registration data set as described by the ICMJE. For JAMA, the acceptable trial registries include the following: Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au); ClinicalTrials.gov (http://www.clinicaltrials.gov); ISRCTN Register (http://isrctn.org); the Nederlands Trial Register (http://www.trialregister.nl/trialreg/index.asp);and UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr). Clinical trials for which patient enrollment began after July 2005 should have been registered before the onset of patient enrollment. All clinical trials, regardless of when they were completed, must have been registered and these trials, as well as secondary analyses of the original trial data, must include the trial registration number in the abstract of the manuscript at the time of submission. JAMA's requirement for trial registration differs somewhat from requirements for registration in the recently enacted Food and Drug Amendments Act of 200711; for instance, JAMA requires registration of all RCTs (except for phase 1 trials) that randomize human research participants to an intervention, not only those trials involving drugs or devices subject to provisions of the Federal Food, Drug, and Cosmetic Act.
Second, authors of clinical trials should follow the CONSORT guidelines12 for reporting RCT results, including submitting a detailed patient flow diagram. For efficacy trials, the primary results should be presented based on intention-to-treat analysis, including and accounting for all randomized patients in the analysis, and if necessary, using appropriate methods to account for missing data (such as imputation methods, baseline values carried forward, etc). Other analyses, such as "completers" or "per-protocol" analyses, may be reported, but the intention-to-treat analysis generally should be reported as the primary analysis. In addition, authors are encouraged to submit protocols of RCTs along with their manuscripts.
Third, for all RCTs, data analysis must be conducted by an academic statistician. For industry-sponsored RCTs in which the data analysis is conducted only by statisticians employed by a company sponsoring the research, JAMA requires that a statistical analysis also be conducted by an independent statistician at an academic institution, such as a medical school, academic medical center, or government research institute, that has oversight over the person conducting the analysis and that is independent of the commercial sponsor.13 The independent statistician should review the study protocol and determine the appropriateness of the prespecified data analysis plan, should receive the entire raw data set, and should conduct an independent data analysis; the results of the independent analysis should be the results reported in the manuscript.
While this approach involves additional effort, time, and cost, the independent verification of data and analysis provides an important additional level of institutional oversight. The independent analysis not only increases the credibility of these studies, but also should help to avoid the perception of and potential for biased reporting that may result from the inherent conflict of interest present when the data management and statistical analysis are conducted only by employees of the sponsor that stands to benefit from the study results. To our knowledge, JAMA is the only general medical journal with this policy. Since implementation of this policy for independent statistical analysis in 2005,13 the number of RCTs submitted to JAMA has continued to increase each year.
In addition, to provide a resource for authors and to facilitate submission to JAMA, authors of RCTs are strongly encouraged to contact JAMA editors for inquiries about the suitability of their trial (completed, nearing completion, or ongoing) for potential publication in JAMA; information about timelines for submission, review, and editorial decisions; and other questions and issues. A listing of the JAMA editors along with their specialty area or topic area of expertise and e-mail contact information is included in the Table. In addition, for major RCTs that have immediate clinical implications, authors are encouraged to request consideration for JAMA-EXPRESS14 to determine whether the manuscript qualifies for expedited review and publication, and perhaps coordination of publication with presentation at a major scientific meeting. For RCTs that qualify for JAMA-EXPRESS, the median time from submission to publication is 42 days.
|
|
|
|
Table. JAMA Editors, Contact Information, and Areas of Expertise
|
|
|
JAMA's large circulation, high impact factor, prompt time to publication, and frequent media coverage provide an ideal mechanism for wide dissemination and communication of results of RCTs to physicians, other health care professionals, the medical research community, policy makers, and the public. We invite and encourage authors to consider JAMA as their journal of first choice for publication of important RCTs.
AUTHOR INFORMATION
Financial Disclosures: None reported.
Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association.
Author Affiliations: Dr Fontanarosa (phil.fontanarosa{at}jama-archives.org) is Executive Deputy Editor and Dr DeAngelis is Editor in Chief, JAMA.
REFERENCES
|
1. JAMA's Key and Critical Objectives. http://jama.ama-assn.org/misc/aboutjama.dtl. Accessed December 11, 2007.
2. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial. JAMA. 2002;288(3):321-333.
FREE FULL TEXT
3. Anderson GL, Limacher M, Assaf AR; et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291(14):1701-1712.
FREE FULL TEXT
4. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981-2997.
FREE FULL TEXT
5. Vogel VG, Constantino JP, Wickerham DL; et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006;295(23):2727-2741.
FREE FULL TEXT
6. Nissen SE, Tsunoda T, Tuzcu EM; et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003;290(17):2292-2300.
FREE FULL TEXT
7. Shaddy RE, Boucek MM, Hsu DT; et al. Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA. 2007;298(10):1171-1179.
FREE FULL TEXT
8. Instructions for authors. JAMA. 2008;299(1):jin022008. http://jama.ama-assn.org/misc/ifora.dtl. Accessed December 12, 2007.9. DeAngelis CD, Drazen JM, Frizelle FA; et al. Is this clinical trial fully registered? a statement from the International Committee of Medical Journal Editors. JAMA. 2005;293(23):2927-2929.
FREE FULL TEXT
10. Laine C, Horton R, DeAngelis CD; et al. Clinical trial registration: looking back and moving ahead. JAMA. 2007;298(1):93-94.
FREE FULL TEXT
11. Food and Drug Amendments Act of 2007. Pub L 110-85. September 27, 2007.12. The CONSORT statement. http://www.consort-statement.org/index.aspx?o=1011. Accessed December 10, 2007.13. Fontanarosa PB, Flanagin A, DeAngelis CD. Reporting conflicts of interest, financial aspects of research, and role of sponsors in funded studies. JAMA. 2005;294(1):110-111.
FREE FULL TEXT
14. Winker MA, Fontanarosa PB. JAMA-EXPRESS: rapid peer review and publication. JAMA. 1999;281:1754-1755.
FREE FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Reporting Mortality Findings in Trials of Rofecoxib for Alzheimer Disease or Cognitive Impairment: A Case Study Based on Documents From Rofecoxib Litigation
Psaty and Kronmal
JAMA 2008;299:1813-1817.
ABSTRACT
| FULL TEXT
|
