Given that pharma manipulates in many ways the all trials they fund, and yet half of all clinical trials go unpublished because of negative results, this this indicates that most drugs are not worth their side effects.  A comprehensive account of how pharma does tobacco science is presented by Prof. Ben Goldacre’s, MD in Bad Pharma (2013).  One methods is to publish only favorable results.  Inferior treatment entails harm. 

Since clinical trials are funded by pharma or a government regulatory agency that promotes pharma’s interest, the failure to publish or complete a clinical trial is, it can be assumed that in over 85% of the cases to be the results of an unfavorable outcome for pharma.  Given that positive bias is the norm in 100% of the cases (found in the only large-scale review of 74 published journal articles compared to the clinical trial raw data), the results must be so significantly contrary to the desired outcome, that a biased journal article is insufficient to cover up the negative results.  And it gets worse, because by design all of those clinical trials are by design set up to produce favorable results.  All this is to be expected by an industry that has a financial incentive to have favorable outcomes. 

The reason for so many unpublished and ended early trials is that the very drug or medical procedure involves a drug or procedure whose important endpoints are negative in the population that favors a positive outcome for pharma—thus not in the real-world treatment population.  The www.healthfully.org/rc site has exposed many of those fundamentally flawed treatments. This deception is counter to the belief of those patients who out of public spirit agree to partake in a clinical trial, and also the physicians who recruit patient and gather data on their patients.  Not published trials entails that the pool of published trials is misleadingly positive; and this is all that conscientious doctors have to go on.  For the other 90% of doctors, they simply follow the recommendation of pharma’s key opinion leaders, who spoon-feed the favorable results to them in the required continuing education classes.  For why so many use junk treatments click on this link. The results are similar for clinical trials of drugs.

Discontinuation and non-publication of surgical randomised controlled trials: observational study

BMJ 2014; 349 British Medical Journal, 11/4/14

Abstract

Objective To determine the rate of early discontinuation and non-publication of randomised controlled trials involving patients undergoing surgery.

Design Cross sectional observational study of registered and published trials.

Setting Randomised controlled trials of interventions in patients undergoing a surgical procedure.

Data sources The ClinicalTrials.gov database was searched for interventional trials registered between January 2008 and December 2009 using the keyword “surgery”. Recruitment status was extracted from the ClinicalTrials.gov database. A systematic search for studies published in peer reviewed journals was performed; if they were not found, results posted on the ClinicalTrials.gov results database were sought. Email queries were sent to trial investigators of discontinued and unpublished completed trials if no reason for the respective status was disclosed.  [Often the excuse made for early termination is that of harm done by the drug.  But this is all the more reason to sound the warning over that drug; however, the norm is to burry the bodies with the study—see Vioxx for a classic example at http://en.wikipedia.org/wiki/Rofecoxib, which has some industry positive spin.]

Main outcome measures Trial discontinuation before completion and non-publication after completion. Logistic regression was used to determine the effect of funding source on publication status, with adjustment for intervention type and trial size.

Results Of 818 registered trials found using the keyword “surgery”, 395 met the inclusion criteria. Of these, 21% (81/395) were discontinued early, most commonly owing to poor recruitment (44%, 36/81). The remaining 314 (79%) trials proceeded to completion, with a publication rate of 66% (208/314) at a median time of 4.9 (interquartile range 4.0-6.0) years from study completion to publication search. A further 6% (20/314) of studies presented results on ClinicalTrials.gov without a corresponding peer reviewed publication. Industry funding did not affect the rate of discontinuation (adjusted odds ratio 0.91, 95% confidence interval 0.54 to 1.55) but was associated with a lower odds of publication for completed trials (0.43, 0.26 to 0.72). Investigators’ email addresses for trials with an uncertain fate were identified for 71.4% (10/14) of discontinued trials and 83% (101/122) of unpublished studies. Only 43% (6/14) and 20% (25/122) replies were received. Email responses for completed trials indicated 11 trials in press, five published studies (four in non-indexed peer reviewed journals), and nine trials remaining unpublished.

Conclusions One in five surgical randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable. This represents a waste of research resources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks. To promote future efficiency and transparency, changes are proposed to research governance frameworks to overcome these concerns.

Positive bias averaged 32% (range 11 to 69%) in a NEJM article, 2008.  The study of neuroleptic drugs made a comparison of 74 journal articles to the raw data which was obtained by FOIA (Freedom of Information Act) from the FDA. See http://healthfully.org/index/id9.html, or http://content.nejm.org/cgi/content/short/358/3/252