Some drug companies unwilling to share unredacted trial protocols

A study has found that half of drug company trial protocols have information deleted from key sections of the protocol, with the extent of redactions often so vast as to render the protocol useless for identifying discrepancies with subsequent publications.

The study authors, from the Nordic Cochrane Centre in Copenhagen, requested access to 78 commercial and non-commercial trial protocols approved by a research ethics committee in Denmark, under the Freedom of Information Act.  It took 3 years, assurances that individual trial data would not be identified, and legal action (instituted by Sanofi-Aventis) to obtain all the requested protocols.

The researchers found that 17 of 34 included protocols for commercially sponsored trials were redacted, compared to 2 of 36 non-commercially sponsored trials.  When researchers examined the redactions in the commercially sponsored trials, they found that data was withheld from sections of the protocol where there is evidence of substantial problems with the trustworthiness of published drug trials.  This includes the definition and analysis of primary outcomes, sample size, interim analysis and sponsor access to data during trial conduct.

According to the researchers, “The amount of redactions in the protocols we received was so vast that it made them rather useless for research purposes, e.g. for assessing the ethical justification for the studies and to identify discrepancies with subsequent publications.” Everything about the analysis of the primary outcomes was redacted in almost half (8/17) of the protocols, and a further 6 protocols had partially redacted information on primary outcomes or it was considered unclear whether the section was redacted or not mentioned in the protocol.  Drug companies with the highest percentage of variables redacted or unclear in their protocols included Novo Nordisck with 82%, Merck Sharp & Dohme with 86% and Sanofi-Aventis with 95%.

The researchers could not identify any legitimate rational for the redactions they observed.

While drug company reluctance to provide key trial information, such as the trial protocol is unsurprising,  the extent of redactions made to protocols by some companies as revealed in this study, is disturbing, and the nature of the redactions- relating mostly to the analysis and description of primary outcomes, extremely concerning. Trial protocols are crucial for detecting misreporting of trials. Without them we can’t know if we are being presented with a biased subset of information.  Ultimately, this impacts patient and clinicians’ abilities to make sound, informed healthcare decisions.

The findings of this study further widen the ‘credibility gap’ around industry sponsored research. The actions taken by some companies in this study are in direct contrast to the pharmaceutical industries own recommendations for closing this gap, specifically Recommendation 7 which is to “Provide access to more complete protocol information’. This study suggests that calls (over several decades), to make key trial documents public have gone largely unheard, and even calls from within, “The larger issue is how do we face the outside world when they begin to criticize us for suppressing data…” (AstraZenica publications manger in internal email 6 Dec 1999) unheeded. Whether studies such as this one, through exposing industries efforts to manipulate the interpretation of drug trial data, lead to a change in the status quo, remains to be seen.

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