AUTH/3158/2/19 - Employee v Servier

Arrangements for an advisory board

  • Received
    05 February 2019
  • Case number
    AUTH/3158/2/19
  • Applicable Code year
    2016
  • Completed
    30 May 2019
  • No breach Clause(s)
  • Additional sanctions
  • Appeal
    No appeal
  • Review
    Published in the May 2020 Review

Case Summary

A contactable complainant who described him/ herself as a Servier employee complained about an advisory board on the management of metastatic colorectal cancer (mCRC) held on 23 June 2017.  Servier marketed Lonsurf (trifluridine/tipiracil) which was used in certain patients with mCRC.

The complainant noted that advisory boards were meant to seek answers to unknown questions.  The complainant alleged that from the beginning, two senior managers decided that the representatives should influence which health professionals should be invited to the advisory board.  According to the complainant, one of the senior managers nominated health professionals who contributed heavily to sales and representatives suggested and got their favourite health professional to attend.  The other senior manager then added a few health professionals that he/she knew well and who had attended a previous advisory board in 2016 on very similar topics.  The complainant provided a copy of an email, between senior managers, sent after the advisory board, which he/she stated clearly acknowledged that attendees were selected by representatives and medical science liaison (MSL) staff.  The complainant further alleged that a colleague in medical was put under extreme pressure from a more senior commercial manager to accept recommendations for health professional attendees.

With regard to content, the complainant explained that in 2017, some representatives pushed the idea that neutropenia, a common and at times serious side effect of Lonsurf, was a predictor of efficacy ie neutropenia meant that the medicine was working.  This was challenged within the company and although some representatives were reprimanded by their local MSL for compromising patient safety, Servier continued to pursue the line that ‘neutropenia was an indicator of efficacy’.  At the advisory board in question, a number of case studies were discussed on this topic and clinicians shared examples of neutropenia and other adverse events; however, no effort was made to document these via pharmacovigilance or adverse event reporting.  The complainant alleged that this clearly compromised patient safety.

The complainant stated that Servier put a positive spin on neutropenia because it had recently been reported that the incidence of neutropenia and febrile neutropenia was higher in clinical practice than previously documented.  Rather than protecting patient safety and ensuring that representatives were adequately briefed on this finding, Servier promoted the idea that neutropenia was good and equalled efficacy.  The complainant stated that evidence of this could be seen in the advisory board agenda and also in an email between senior managers in which it was stated that ‘Neutropenia being a predictor (or not) of response’ would be discussed.  This showed the carefree attitude towards patient safety.

In summary, the complainant alleged that the advisory board was organised as a meeting for loyal users of Lonsurf and patient safety was compromised by not reporting adverse events.  Representatives influenced attendee selection.  The complainant further alleged that given the involvement of the commercial colleagues, the advisory board was a disguised promotional meeting; if this was not so then why did one senior manager in medical acknowledge the commercial functions in an email immediately after the advisory board, and not include a relevant medical colleague and team of MSLs?

The detailed response from Servier is given below.

The Panel noted that while it was acceptable for companies to pay health professionals and others for relevant advice, the arrangements for advisory boards had to comply with the Code.  To be considered a legitimate advisory board the choice and number of participants should stand up to independent scrutiny; each should be chosen according to their expertise such that they would be able to contribute meaningfully to the purpose and expected outcomes of the meeting.

The Panel noted the complainant’s allegation that advisor selection was influenced by representatives and a senior manager who nominated health professionals who contributed heavily to sales.  The Panel noted Servier’s submission that one of the meeting objectives was to gain feedback on the practical use of Lonsurf and so advisors needed to have clinical experience with the medicine.  In the Panel’s view, it was not necessarily unacceptable for representatives to identify health professionals with relevant clinical experience to provide the clinical insights required.  Regardless of the source of the recommendation, the criteria for selection must be directly related to the identified need and must not be, inter alia, an inducement to prescribe a medicine or a reward for previous prescriptions.  The Panel noted Servier’s submission that the final decision of who to invite lay with the medical department.

The Panel further noted the complainant’s allegation that, to increase numbers, some health professionals were invited who had attended a very similar advisory board the previous year.  The Panel noted Servier’s submission that some of the attendees had indeed attended one or both of two previous Lonsurf advisory boards in January 2016 (before the product launch) and one of the two held in May 2016.  The Panel noted the time-periods between the advisory boards, the different time-points in the product’s lifecycle, and the largely different meeting objectives.

The Panel noted it comments above.  A judgement had to be made on the available evidence.  In the Panel’s view, the complainant had not proved, on the balance of probabilities, that the selection of advisors was not directly related to the identified need or that the selection was an inducement to prescribe, supply, administer, recommend, buy or sell any medicine.  No breach of the Code was ruled.

The Panel was concerned about the complainant’s serious allegation that one manager was put under extreme pressure to accept recommendations for attendees from a more senior manager but noted that he/she had provided no evidence in this regard.  The Panel considered that the complainant had not discharged the burden of proof and no breach of the Code was ruled.

The Panel noted the allegation that promoting neutropenia with Lonsurf as a predictor/indicator of response at the meeting demonstrated the company’s carefree attitude towards patient safety.  The complainant provided a copy of a presentation used at the meeting entitled ‘Neutropenia – is it a predictor of response to trifluridine/tipiracil?’.  The Panel noted that the objectives of the advisory board did not include obtaining feedback on neutropenia being a predictor of response.  This topic was allocated 45 minutes on the agenda, including a 10-minute presentation.  The Panel noted Servier’s submission that the conclusion in the executive summary of the meeting minutes stated: ‘Neutropenia is a manageable toxicity, but certainly not a predictor of response, but (it) is more of a reflection that an adequate dose has been given. Observations of improved overall survival (OS) and progression free survival (PFS) with the neutropenia cohort is more likely a testimony to them being a biologically different group, and not strong enough evidence to change clinical practice i.e. to induce neutropenia in patients who don’t experience it’.

The Panel was concerned to note that the briefing documents to this session’s speaker and to the meeting chair stated: ‘To their knowledge does any company leverage this information in the promotion of their products?’ and ‘If a patient did not experience neutropenia what would this mean for the prescribing of trifluridine/tipiracil?’. 

In the Panel’s view, Servier intended to get feedback on neutropenia as a predictor of response with Lonsurf, including use of such a claim in the promotion of Lonsurf.  Feedback from the advisors included ‘A degree of caution should be exercised if using this argument commercially …’ and ‘These observations of improved [progression free survival] and [overall survival] do not suggest that clinicians should induce neutropenia in patients who don’t present with it (i.e. by increasing the dose) for improved outcomes’. 

Whilst the Panel had serious concerns about the acceptability of claiming that neutropenia was a predictor of response, it considered that it was not necessarily unacceptable to discuss the clinical data in an advisory board in order to gain advice.  There was no evidence that the claim was used to promote Lonsurf.  Noting its comments above, the Panel considered that the complainant had not discharged the burden of proof in this regard and ruled no breach of the Code.

The Panel then considered the allegation that Servier had not reported the adverse events from patient cases.  The title page of the clinical case presentation slides used at the meeting included the statement ‘Please note that all of the following case scenarios are hypothetical’.  The speaker’s briefing document stated that this section of the advisory board was not to prompt the discussion of adverse events ie events related to a specific patient.  It also stated that if any events were discussed, Servier would have to follow them up.  The chair’s briefing had similar statements and that the speaker would make attendees aware of the pharmacovigilance statement.  The Panel noted Servier’s submission that, from the meeting minutes, there was no specific patient or group of patients discussed, and adverse events were discussed only in general terms prompted by the hypothetical cases presented. 

The Panel noted the importance of reporting adverse events and that Servier had briefed the speaker and chairman.  It appeared that if adverse events that required reporting had been raised, relevant personnel knew what to do.  The Panel considered that the evidence supplied by the complainant did not show, on the balance of probabilities, that Servier had not met the requirements of the Code in relation to adverse event reporting and therefore ruled no breach of the Code.

The Panel noted the further allegation that some Servier representatives had promoted the concept of neutropenia with Lonsurf as an indicator of efficacy and that this compromised patient safety.  The Panel noted that, inter alia, briefing material must not advocate, directly or indirectly, any course of action which would be likely to lead to a breach of the Code.  The Panel noted Servier’s submission that its sales materials and briefing documents did not mention, claim or compare any evidence that neutropenia was an indicator of efficacy and that it had no record of representatives being reprimanded for such activity as alleged.  The Panel considered that as the complainant had provided no evidence to support this allegation, he/she had not discharged the burden of proof.  The Panel therefore ruled no breach of the Code.

The Panel noted the complainant’s general allegation that the advisory board in question was a disguised promotional meeting for loyal Lonsurf customers.  The Panel noted that although a disputed email was not copied to the MSLs or a relevant member of the medical team and the medical team member was not acknowledged in the email, this did not in itself indicate that the advisory board was a disguised promotional meeting as alleged.  Nor did the role of commercial colleagues necessarily indicate that the advisory board was a disguised promotional meeting as alleged.

The Panel noted that ten health professionals and three Servier employees attended the meeting in question.  The Panel noted the meeting objectives, the expected outputs in the certified rationale document and Servier’s submission regarding the expertise and experience of the advisors selected in relation to the advice sought.  Servier had retrospectively analysed sales data and found no evidence that any of the advisors were ‘loyal users of Lonsurf’ as alleged.

The Panel noted from the agenda that just over 80% of the meeting which was held from 10am-4pm was allocated to discussion.  There was 40 minutes of presentation time.  Feedback and advice obtained from the advisory board was documented in the meeting executive summary along with actions for Servier. 

The Panel noted its comments above.  A judgement had to be made on the evidence provided by the parties.  Whilst there were some concerns, in the Panel’s view, the complainant had not proved, on the balance of probabilities, that the advisory board meeting was disguised promotion and no breach of the Code was ruled. 

The Panel noted that Clause 2 was used as a sign of particular censure and reserved for such use.  The Panel noted its comments and rulings above and ruled no breach of Clause 2.