BMJ 2017;356:j337 Study (Published 07 February 2017)
Our findings do not support the aspiration of the German Medicinal Products Act that post-marketing studies serve to improve long term drug safety surveillance.
In contrast, we found evidence that drug safety could be jeopardised by the current practice, as post-marketing studies are expected to contribute to pharmacovigilance, but in reality their data and results are treated as business secrets.
Our data support the view that the high remunerations paid by the sponsor to the participating physician could be serving commercial purposes rather than transparent and effective pharmacovigilance.
In our opinion the major problem with post-marketing studies is the confidentiality clauses in the contracts between physicians and sponsors. These contracts impose a major obstacle to scientific evaluation and discussion of post-marketing studies. In the interest of drug safety and public health, post-marketing surveillance should become more transparent. Data about and from such studies should no longer be considered confidential business information but should be made available to independent scientific evaluation and public scrutiny. Such increased transparency would allow future researchers to evaluate whether the changes in 2012 to EU pharmacovigilance legislation have been associated with any material improvements in the situation.
The importance of advising GPs and clinicians on their indispensable role in detecting, diagnosing, and reporting adverse drug reactions cannot be overestimated.
What is already known on this topic
- Systematic evaluations of post-marketing industry funded trials are sparse
- The few studies available have criticised post-marketing studies for their low scientific value and lack of scientific integrity and for being seeding trials masking marketing interests of the sponsors as research
- Current legislation relies on post-marketing studies for drug safety surveillance
What this study adds
- Post-marketing studies are not serving as a key tool for drug safety surveillance, at least among those registered in Germany
- Sample sizes are generally too small to allow for the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor about all data, including adverse drug reactions
- The post-marketing studies analysed are doing no measurable good to patients and could be taking resources away from more effective pharmacovigilance systems
Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies, BMJ 2017;356:j337, 07 February 2017.
To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act.
Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10.
Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany.
Main outcome measures
Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions.
Image credit The BMJ Fig 3 : Example of confidentiality agreement for post-marketing study (source: notification sent by Merck Serono on 18 March 2010 regarding post-marketing study of cladribine)
Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals.
Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor. High remuneration and strict confidentiality clauses in these studies could influence the physicians’ reporting behaviours of adverse drug reactions.