Chapter 10: Article 2
Our medical journals are currently in shambles, because the scientific research published within was compromised through pharmaceutical influence. Dr. Ben Goldacre explained the infiltration and danger of publication bias. in his TedMED Talk titled, What doctors don't know about the drugs they prescribe. He explained that research that shows positively towards pharmaceutical drugs is far more likely to be published, and research that shows unfavourably for a drug often goes missing and isn't published.
Research from 2015 analyzed trials that were registered in ClinicalTrials.gov, and that analysis showed that the government and pharmaceutical companies are the biggest funders of research. The data showed that pharma funded research accounted for at least 36% of all registered research, and pharma funded research surpassed government funded research 4.5:1.
A 2016 article by STAT media group explained how frequently research goes unpublished. STAT's article was titled, Many clinical trials’ findings never get published. Here’s why that’s bad. The article states (emphasis mine):
New research suggests that nearly half of all clinical trials involving kids go unfinished or unpublished — either because the researchers lose interest in the work or take up more pressing projects, or, in some cases, because the companies that funded the studies don’t want the results to get out.
....industry money was a significant predictor of whether data would see the light of day. Studies that received industry funding were more than twice as likely as those with non-industry grants — such as government or foundation money — to be unpublished two years after the end of the project, and more than three times as likely after three years.
Although recent research shows that half of all pharma funded clinical research goes unpublished, that only accounts for the research that is known about because it was registered within a period of time after the trial began. There is also a substantial body of research that is being conduct without any awareness of it. This is because not only was the research never published, it also was never registered at the beginning of the trial.
A study that analyzed this stated (emphasis mine):
This study and approach are novel for at least five reasons. First, we evaluated the transparency around individual new drugs. Previous studies generally evaluate transparency on the trial level....When a new drug enters the market, the trials we evaluated in our rating system contain the safety and efficacy profile for that drug, and all, or nearly all, available evidence to inform clinical practice.
Second, we used FDA approval packages as a key data source, because they characterise all clinical trials supporting new drug approvals. Prior studies evaluate the transparency of already registered trials in ClinicalTrials.gov, which provide limited insights into the many unregistered studies. Third, we focused on large companies because, as a group, they sponsor a significant portion of the trials conducted annually and the majority of new drug applications (NDAs) submitted to the FDA. Also, they were expected to have the infrastructure to comply with regulatory and ethics standards. Thus, we likely captured a best-case scenario.
The conclusion of this research was that only a fraction of the companies complied with all disclosure requirements. The research stated:
2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge.
...While nearly two-thirds of clinical trials, per drug, were publicly disclosed, there was wide variation among drugs and companies. At first approximation, it may seem difficult to understand failures to comply with federal law, now 8 years old, whose origins track back to 1997, and even more difficult to understand failures to meet the over-riding ethics obligation that human research be designed to contribute to generalisable knowledge.
Another paper explained why it's important that research be published "to contribute to generalizable knowledge," stating (emphasis mine):
...selective trial dissemination... represents a violation of the rights of human research subjects, as experimenting on humans is largely justified by its potential to contribute to generalisable knowledge (as stated in the 1981 US Common Rule).
Further to that, the pharmaceutical industry pays a considerable amount of funding to the journals themselves, through advertising sponsorship. The journals need this advertising funding to remain profitable. If pharma learns a medical journal intends to publish an independent study that does not show favourabe support towards a pharmaceutical product, the company has been known to threaten to withdraw their advertising sponsorship. This is why you sometimes see a medical journal publish research, and then later retract that paper with no reason given.
It’s for all of these reasons that both Dr. Richard Horton, the Editor-in-Chief of the Lancet and Dr. Marcia Angell the former Editor-in-Chief of the New England Journal of Medicine have stated we can no longer trust and rely upon the research within the medical journals (Ch2: Part 1).
Dr. Richard Horton published a letter within the Lancet, a letter which says:
Journal editors deserve their fair share of criticism too. We aid and abet the worst behaviours. Our acquiescence to the impact factor fuels an unhealthy competition to win a place in a select few journals. Our love of “significance” pollutes the literature with many a statistical fairy-tale.
...Can bad scientific practices be fixed? Part of the problem is that no-one is incentivised to be right. Instead, scientists are incentivised to be productive and innovative.
And Dr. Marcia Angell was quoted as saying (Link Here):
It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of the New England Journal of Medicine.
As a protective measure for public health, it is necessary that the regulatory agencies require that ALL research be registered and published. Until that time however, we must be cautious in how we review the scientific literature published within the medical journals, recognizing that current health regulation has allowed for the creation of a data library that has become heavily biased from pharmaceutical influence.
CONTINUE on to the next article Ch10: Part 3
Dr. Ben Goldacre - TedMED Talk Here
Pharma outspends Government on research, funding 4.5 studies for every 1 Governmentally funded study Here
STAT article: Many clinical trials’ findings never get published. Here’s why that’s bad Here
British Medical Journal: Clinical trial registration, reporting, publication and FDAAA compliance Here
British Medical Journal - Why research needs to contribute to generalizable knowledge Here
British Medical Journal - Potential bias based on reprint revenue Here
Dr. Richard Horton - Here
Dr. Marcia Angell - Here