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Letters |

Guest Authorship, Mortality Reporting, and Integrity in Rofecoxib Studies

Kent R. Johnson, MD; Marissa N. D. Lassere, MBBS, PhD
JAMA. 2008;300(8):900-906. doi:10.1001/jama.300.8.900-a
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To the Editor: The study by Drs Psaty and Kronmal1 and the accompanying Editorial by Drs DeAngelis and Fontanarosa2 regarding rofecoxib illustrate the recurring problem of discretionary or data-driven analysis. Given the possibility of selective analysis based on observed data and the risk of positive results due to chance alone, it is critical to know in detail which analyses were prespecified and when the prespecification occurred. This can only be done via a full protocol repository, as we suggested in 2002.3 Our proposal would establish a secure real-time repository for protocols, amendments, and statistical analysis plans. The material would be kept confidential for intellectual property reasons during the clinical trial and its analysis and then made public at the time of publication. The proposal has yet to be implemented, although the Food and Drug Administration (FDA) Act of 2007 (US HR3580), which provides for a Web site for results of all phase 2, 3, and 4 trials,4 also requires posting the protocol.

The rofecoxib data reported in the study by Psaty and Kronmal illustrate that the ascertainment of even a hard end point like mortality can be modulated by varying the appropriate window of time used to capture the event of interest. With other end points, especially composite end points, the situation is rife with possibilities of changing results by discretionary ascertainment. This is why one of the last aspects of the protocol to be finalized is often the statistical analysis plan. However, with no protocol or a timeline documentation of its provenance, these details are never made public so that it is not possible to see how published analyses compare with protocol-specified analyses. This transparency is needed to be confident in the validity of the results.

AUTHOR INFORMATION

Financial Disclosures: None reported.

REFERENCES

Psaty BM, Kronmal RA. Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment: a case study based on documents from rofecoxib litigation.  JAMA. 2008;299(15):1813-1817
PubMedCrossRef
DeAngelis CD, Fontanarosa PB. Impugning the integrity of medical science: the adverse effects of industry influence.  JAMA. 2008;299(15):1833-1835
PubMedCrossRef
Lassere M, Johnson K. The power of the protocol.  Lancet. 2002;360(9346):1620-1622
PubMedCrossRef
 Food and Drug Administration Amendments Act of 2007 [HR 3580, enacted by the House and Senate; Pub L No. 110-85]. http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_bills&docid=f:h3580eh.txt.pdf. Accessed April 25, 2008

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Psaty BM, Kronmal RA. Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment: a case study based on documents from rofecoxib litigation.  JAMA. 2008;299(15):1813-1817
PubMedCrossRef
DeAngelis CD, Fontanarosa PB. Impugning the integrity of medical science: the adverse effects of industry influence.  JAMA. 2008;299(15):1833-1835
PubMedCrossRef
Lassere M, Johnson K. The power of the protocol.  Lancet. 2002;360(9346):1620-1622
PubMedCrossRef
 Food and Drug Administration Amendments Act of 2007 [HR 3580, enacted by the House and Senate; Pub L No. 110-85]. http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_bills&docid=f:h3580eh.txt.pdf. Accessed April 25, 2008
August 27, 2008
Garret A. FitzGerald, MD
JAMA. 2008;300(8):900-906.
August 27, 2008
Carlo Patrono, MD
JAMA. 2008;300(8):900-906.
August 27, 2008
Christopher J. Hawkey, DM
JAMA. 2008;300(8):900-906.
August 27, 2008
Steven Ferris, PhD; Douglas Galasko, MD; Louis Kirby, MD
JAMA. 2008;300(8):900-906.
August 27, 2008
Richard Balon, MD
JAMA. 2008;300(8):900-906.
August 27, 2008
Serban-Dan Costa, MD, PhD
JAMA. 2008;300(8):900-906.
August 27, 2008
Hervé Maisonneuve, MD
JAMA. 2008;300(8):900-906.
August 27, 2008
Hean T. Ong, MBBS; Jin S. Cheah, MBBS
JAMA. 2008;300(8):900-906.
August 27, 2008
Peter A. Lachenbruch, PhD; Ronald Wasserstein, PhD
JAMA. 2008;300(8):900-906.
August 27, 2008
Bruce M. Psaty, MD, PhD; Richard A. Kronmal, PhD
JAMA. 2008;300(8):900-906.
August 27, 2008
Joseph S. Ross, MD, MHS; David S. Egilman, MD, MPH; Harlan M. Krumholz, MD, SM
JAMA. 2008;300(8):900-906.
August 27, 2008
Catherine D. DeAngelis, MD, MPH; Phil B. Fontanarosa, MD, MBA
JAMA. 2008;300(8):900-906.
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