AUTH/3091/9/18 - Director v UCB

Clinical trial disclosure

  • Received
    12 September 2018
  • Case number
    AUTH/3091/9/18
  • Applicable Code year
    2016
  • Completed
    22 July 2019
  • No breach Clause(s)
  • Breach Clause(s)
  • Sanctions applied
    Undertaking received
  • Additional sanctions
  • Appeal
    No appeal
  • 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 UCB 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.

The detailed response from UCB is given below.

General detailed comments from the Panel are given below.

The Panel noted the data in Goldacre et al in that results for five of UCB’s due trials had not been reported on EUCTR; the disclosure percentage was 87.5%.

The Panel noted UCB Pharma’s submission that although UK sites were planned in trial SP935 , the trial was cancelled on 26 March 2008 before any patients were enrolled and so no data was collected. The Panel therefore ruled no breaches of the Code including no breach of Clause 2 in relation to trial SP935.

The Panel noted UCB Pharma’s submission that trial RA0134 had no UK involvement, no UK sites, investigators or patients and UCB Pharma Ltd was not involved in the funding nor conduct of the clinical trial. The Panel considered that as there was no UK involvement, the matter did not come within the scope of the UK Code. No breach of the Code was ruled in relation to trial RA0134.

The Panel noted UCB‘s submission that trials RA0056, RA0057 and CD0001 related to a product which was out-licensed from UCB to R-Pharm in June 2013, upon completion of the Phase II programme (to which RA0056, RA0057 and CD0001 belong) and before the start of the Phase III programme (which would be the responsibility of R-Pharm).

The Panel noted that the sponsor for trials RA0056 and RA0057 was UCB Biosciences Inc, UCB’s entity in the US. The Panel noted UCB Pharma’s submission that the UK was not involved in funding or conducting these two trials but both had sites in the UK.

The Panel noted that trial RA0056 had 10 study sites in UK and completed on 29 June 2012. The Panel noted UCB’s submission that study results were published in a peer-reviewed journal in 2014. However, 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. 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 that regard. The Panel was unsure whether or not the results were now disclosed on EUCTR but noted that they were published elsewhere as stated above. The Panel therefore did not consider that in the circumstances a breach of Clause 2 was warranted and ruled accordingly.

The Panel noted that trial RA0057 had 19 sites in UK and completed on 5 August 2013. However, 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. 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 that regard. The Panel was unsure whether or not the results were now disclosed on EUCTR or elsewhere. On balance, the Panel did not consider that in the circumstances a breach of Clause 2 was warranted and ruled accordingly.

The Panel noted UCB Pharma’s submission that trial CD0001 was sponsored by UCB Biosciences GmbH, Inc, UCB’s entity in Germany. UCB in the UK was not involved in the funding nor conduct of the clinical trial which had no UK sites. The study was prematurely terminated in October 2013, with no patient enrolled. The Panel considered that as there was no UK involvement, the matter did not come within the scope of the UK Code. No breach of the Code was ruled in relation to trial CD0001.

* * * * *

Following its completion of the consideration of four appeals in the clinical trial cases on 18 September 2019 (Cases AUTH/3079/9/18 (Pfizer), AUTH/3087/9/18 (GlaxoSmithKline), AUTH/3118/11/18 (Tesaro) 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 noted that a series of cases had been taken up by the PMCPA as a result of the data published in Goldacre et al. Four cases (Cases AUTH/3079/9/18, AUTH/3087/9/18, AUTH/3118/11/18 and AUTH/3102/9/18) were the subject of an appeal by the respondent companies. Each was determined on its own merits but there were a number of common themes. (Full details can be found in the relevant case reports)

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 that, where companies had merged or the rights to a particular product had been bought or sold, there appeared to be difference of opinion as to which company would be responsible for posting the retrospective results. There were also difficulties in correcting information once posted.

The Appeal Board also noted that, according to Goldacre et al, Phase 1 trial results that were not part of a paediatric plan did not need to be disclosed.

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 was concerned in each case about the failure to disclose the summary results on EUCTR within the timelines advised by the EC Guideline and other relevant advice. In the exceptional circumstances of each case, the Appeal Board did not consider that the late posting of the trial results on the EUCTR as part of a retrospective exercise warranted a breach of the Code particularly in two of the cases as in those the trial results had been publicly disclosed prior to receipt of the complaint. The appeals in the above four cases were successful.

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 were 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. After consideration of the appeals the Appeal Board agreed that Boehringer Ingelheim, UCB, Teva and Allergan should each be offered the opportunity to appeal out of time.’ Allergan and UCB declined the opportunity to appeal and Boehringer Ingelheim. Teva successfully appealed the Panel’s rulings of breaches of the Code.