AUTH/3118/11/18 - Director v Tesaro

Clinical trial disclosure

  • Received
    21 November 2018
  • Case number
    AUTH/3118/11/18
  • Applicable Code year
    2016
  • Completed
    18 September 2019
  • No breach Clause(s)
  • Additional sanctions
  • Appeal
    Appeal by respondent
  • Review
    To be published in the Code of Practice Review

Case Summary

A study published online in the British Medical Journal (12 September 2018) was entitled ‘Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource’ (Goldacre et al 2018).

The study objectives included assessing compliance rates with the European Commission’s requirement that all trials on the EU Clinical Trials Register (EUCTR) posted results to the registry within 12 months of completion (final compliance date 21 December 2016). The study objectives also included identifying features associated with non-compliance, ranking sponsors by compliance and building a tool for live ongoing audit of compliance. The published paper listed the trial sponsors with the highest proportion of trials reported and the trial sponsors with the highest proportion of trials unreported. The results were that of 7,274 trials where results were due, 49.5% (95% confidence interval 48.4% to 50.7%) reported results.

Goldacre et al stated that the European Commission (EC) Guideline required the results of all trials to be reported in structured form on to the register itself. It was possible that some trials that did not report results to EUCTR reported results elsewhere eg in a conference presentation, an academic journal article, as part of a meta-analysis after data were requested by systematic reviewers, or in the grey literature. Such publications did not meet the reporting requirements of the EC Guideline and were therefore outside the scope of the study.

Goldacre et al listed sponsors with more than 50 trials on the EUCTR and did not mention products or specific clinical trials. Goldacre et al gave details of disclosure of clinical trial results for each sponsor.

The Director decided that the Goldacre et al article was such that she had received information from which it appeared that Merck Sharp & Dohme might have breached the Code and decided in accordance with Paragraph 5.1 of the Constitution and Procedure to take the matter up as a complaint (Case AUTH/3086/9/18). Following receipt of the response from Merck Sharp & Dohme the matter was taken up with Tesaro as the medicine was transferred to Tesaro.

The detailed response from Tesaro is given below.

General detailed comments from the Panel are given below.

The Panel noted Tesaro’s submission that the clinical trial in question was about the use of SCH619734 in chronic idiopathic cough and was sponsored by Schering Plough Research Institute in the US, a division of Schering Corporation. The Panel noted Tesaro’s submission that SCH619734 was now known as Varuby (Rolapitant) and was first licensed for sale in the US on 1 September 2015 and was first made commercially available in the US in November 2015. In the UK, Varuby was currently licensed for the prevention of delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy in adults. Rolapitant was not authorised anywhere in the world for chronic idiopathic cough nor being developed for use in that indication. The Panel noted that the trial which was carried out at a single UK site, started on 18 January 2007 and completed on 22 October 2007.

The Panel noted Tesaro’s submission that the summary report of the trial which was dated 23 September 2008 was made available on the EU Clinical Trials Register on 19 October 2018. The Panel noted that the results did not appear to be published on EUCTR within the required timeframe. The Panel therefore ruled a breach of the Code which was appealed by Tesaro. The Panel noted from the evidence before it that there did not appear to have been any formal finding by any judicial authority or appropriate body charged with determining matters in relation to the Commission Guidelines that the company had not complied with the relevant laws and regulations. The Panel therefore ruled no breach of the Code in relation to this trial. The Panel noted that the results were now disclosed on EUCTR and therefore it did not consider that in the circumstances a breach of Clause 2 was warranted and ruled accordingly.

The Appeal Board noted that Article 57(2) of Regulation (EC) No 726/2004 and Article 41(2) of Regulation (EC) No 1901/2006 required that clinical trial data be published on EUCTR. European Commission (EC) Guideline 2012/c302/03 gave guidance as to when the clinical trial results data should be published. According to the guideline posting of results of clinical trials which ended one year or more prior to finalisation of the programming of the relevant database, should be done within 24 months of finalisation of that programming. According to the ‘What’s New’ section of EudraCT public website (post-dated 13 January 2016) the deadline for submission of these results was 21 December 2016. This date was referred to in Goldacre et al. It appeared to the Appeal Board that whilst the regulation mandated disclosure of results on EUCTR, the EC Guideline and other material advised companies how to comply with the regulation including in relation to the timing of such disclosures. The Appeal Board considered that it was within the spirit of the Code and good practice to comply with the EC Guideline in question.

The Appeal Board noted Tesaro had results due for one trial (trial 2006-002164-26), but no results had been posted. The Appeal Board noted the data in Goldacre et al in that as the results for Tesaro’s one due trial had not been reported on EUCTR; the disclosure percentage was therefore 0%.

The Appeal Board noted that the Panel had ruled a breach of the Code for Tesaro’s failure to disclose results by 21 December 2016 or within the required timeframe in relation the trial (trial 2006-002164-26) and this was the subject of the appeal.

The Appeal Board noted from Tesaro’s submission that trial 2006-002164-26, posting on EUCTR was delayed because the trial was related to asset SCH619734, now known as Varuby (rolapitant), which was originally developed by Schering Plough; as a consequence of Schering Plough’s merger with Merck & Co in 2009, rolapitant was divested to OPKO Health Inc. in October 2009. In December 2010, OPKO Health Inc. granted Tesaro Inc. an exclusive licence of the worldwide rights to develop and commercialise rolapitant. The Appeal Board noted that Tesaro understood that the trial in question was conducted and completed at a single UK site by its sponsor, the US based Schering Plough Research Institute, a division of Schering Corporation.

The Appeal Board considered that there would be a difference between action to deliberately hide clinical trial data or systematic failure resulting in non or late disclosure and late disclosure of results as part of a retrospective exercise contrary to non-mandatory timelines due to mitigating factors. The Appeal Board, nonetheless, noted its view above about good practice and disclosure in accordance with the EC Guideline.

The Appeal Board noted from Tesaro’s submission that, on 19 October 2018 before Tesaro was notified of the complaint, the trial results (trial 2006-002164-26) were provided to EUCTR by Tesaro Inc following a request from Merck Sharp & Dohme, which no longer had a right to access the report. The Appeal Board noted Tesaro’s submission about sponsorship of the trial and that it was not an affiliate of, nor did it acquire, the sponsor. Nonetheless, bearing in mind its comments above, the Appeal Board noted that Tesaro Inc had access to, and posted, the trial results.

The Appeal Board was concerned about the failure to disclose the summary results of one trial on EUCTR within the timelines advised by the EC Guideline and other relevant advice. In the exceptional circumstances of this case, the Appeal Board did not consider that the late posting of the results of this trial on the EUCTR as part of a retrospective exercise warranted a breach of the Code, particularly as the results of the trial had already been publicly disclosed and prior to receipt of the complaint. The Appeal Board ruled no breach of the Code. The appeal was successful.

Following its completion of the consideration of the appeal in this case and in Cases AUTH/3079/9/18 (Pfizer), AUTH/3087/9/18 (GlaxoSmithKline) and AUTH/3102/9/18 (Lilly) the Appeal Board noted that the respondent companies in Case AUTH/3084/9/18 (Boehringer Ingelheim), Case AUTH/3091/9/18 (UCB), Case AUTH/3097/9/18 (Teva), and Case AUTH/3099/9/18 (Allergan), accepted the Panel’s rulings of breaches of the Code and had not appealed.

The Appeal Board agreed that Boehringer Ingelheim, UCB, Teva and Allergan should be contacted and informed of the outcome of the appeals in Cases AUTH/3079/9/18, AUTH/3087/9/18, AUTH/3118/11/18 and AUTH/3102/9/18. The PMCPA Constitution and Procedure did not cover this unusual situation where more than one company was involved in a similar set of circumstances and the Appeal Board had taken a different view to the Panel. Boehringer Ingelheim, UCB, Teva and Allergan should each be offered the opportunity to appeal out of time and the appeal process would operate in the usual way. The Appeal Board noted that each cases’ circumstances might differ, and the result of any appeal could not be guaranteed. The reports for Case AUTH/3084/9/18 (Boehringer Ingelheim), Case AUTH/3091/9/18 (UCB), Case AUTH/3097/9/18 (Teva) and Case AUTH/3099/9/18 (Allergan), should be updated to reflect the situation and to cross refer to the cases which were successfully appealed. Allergan and UCB declined the opportunity to appeal. Boehringer Ingelheim and Teva successfully appealed the Panel’s rulings of breaches of the Code.