http://www.thelancet.com/journal/vol356/iss9230/full/llan.356.9230.original_research.9703.1
The uncertainty principle and industry-sponsored
research
Benjamin Djulbegovic, Mensura Lacevic, Alan Cantor, Karen
K Fields, Charles L Bennett, Jared R Adams, Nicole M Kuderer, Gary H Lyman
Divisions of Blood and Bone Marrow Transplantation (B Djulbegovic
MD, M Lacevic MD, Prof K K Fields MD)
and Biostatistics (Prof A Cantor PhD), H Lee Moffitt Cancer Center and Research
Institute at the University of South Florida, Tampa, FL; VA Chicago Health Care
Sysem--Lakeside Division,Chicago, IL (C L Bennett MD); Division of
Hematology/Oncology, Northwestern University Medical School Chicago, IL (C L
Bennett, J R Adams BS); and Division of Hematology/Oncology, Albany Medical
College, Albany, NY, USA (Prof G H Lyman MD, N M Kuderer BS)
Correspondence to: Dr B Djulbegovic, Division of Blood
and Bone Marrow Transplantation, H Lee Moffitt Cancer Centre andResearch
Institute, University of South Florida, 12902 Magnolia Drive Tampa, FL 33612,
USA (mail:djulbebm@moffitt.usf.edu)
Summary
Background Reporting of pharmaceutical-industry-sponsored
randomised clinical trials often result in biased findings, either due to selective
reporting of studies with non-equivalent arms or publication of low-qualitypapers,
wherein unfavourable results are incompletely described. A randomised trial
should beconducted only if there is substantial uncertainty about the relative
value of one treatment versus another. Studies in which intervention and
control are thought to benon-equivalent violates the uncertainty principle.
Methods We examined the quality of 136 published randomised
trials that focused on one disease category (multiple myeloma) and adherence to
the uncertainty principle. To evaluate whether the uncertainty principle was upheld,
we compared the number of studies favouring experimental treatments over standard
ones. We analysed data
according to the source of funding.
Findings Trials funded solely or in part by 35 profit-making
organisations had a trend toward higher quality scores (mean 2·94 [SD 1·3]; median
3) than randomised trials supported by 95 governmental or other non-profit organisations
(2·4 [0·8]; 2; p=0·06). Overall, the uncertainty principle was upheld, with 44%
of randomised trials favouring standard treatments and 56% innovative
treatments (p=0·17); mean and median preference evaluation scores were 3·7
(1·0) and 4. However, when the analysis
was done according to the source of funding, studies funded by non-profit organisations
maintained
equipoise favouring new therapies over standard ones (47% vs 53%;
p=0·608) to a greater extent than
randomised trials supported solely or in part by profit-making organisations
(74% vs 26%; p=0·004).
Interpretation The reported bias in research sponsored
by the pharmaceutical industry may be a consequence of violations of the
uncertainty principle. Sponsors of clinical trials should be encouraged to
report all results and to choose appropriate comparative controls.
Lancet 2000; 356: 635-38
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