The uncertainty principle and industry-sponsored research.
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-quality papers, wherein unfavourable results are incompletely described. A randomised trial should be conducted only if there is substantial uncertainty about the relative value of one treatment versus another. Studies in which intervention and control are thought to be non-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.


RESULTS
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).


CONCLUSIONS
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.
Djulbegovic
B
B
Division of Blood and Bone Marrow Transplantation, H Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa 33612, USA. djulbebm@moffitt.usf.edu
Lacevic
M
M
Cantor
A
A
Fields
K K
KK
Bennett
C L
CL
Adams
J R
JR
Kuderer
N M
NM
Lyman
G H
GH
D015982:Bias; D004345:Drug Industry / Q000191:economics; D006801:Humans; D009101:Multiple Myeloma / Q000191:economics / Q000453:epidemiology / Q000628:therapy*; D018579:Patient Selection; D011336:Probability; D016032:Randomized Controlled Trials as Topic / Q000191:economics / Q000706:statistics & numerical data*; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards* / Q000706:statistics & numerical data*; D012109:Research Support as Topic / Q000706:statistics & numerical data*; D035501:Uncertainty