Key Topic 1: Activities prior to marketing authorization - Scientific exchange
There is no official definition of ‘scientific exchange’, but the term has been used by regulatory authorities to acknowledge that exchange of information during the development of a product needs to be allowed for certain ‘legitimate’ reasons. In addition the term ‘exchange’ implies a two way process in terms of sharing information. This does not preclude the one way provision of off label information, but this should not be the only part of the process.
It is important to distinguish scientific exchange from medical education, because medical education does not allow for sharing of off label information.
In medical education the purpose is to add to the knowledge or skills of the target audience in some way through a teaching or training process.
In scientific exchange there is a sharing of knowledge without a ‘training’ or ‘teaching’ element.
One of the commonest forms of scientific exchange that you will encounter is advisory boards. The following are key considerations for advisory boards:
- There must be a clear and documented business need for the advice
- The number of advisors invited and attending and the duration of the advisory board must not exceed what is reasonably necessary to achieve the objectives of the advisory board
- They must not be attended by sales representatives or their first line managers
- There must be a clear and documented rationale for the choice of advisors and this should stand up to scrutiny
- The agenda must allow enough time for active discussion and input from all of the advisors. Their input must constitute the majority of the agenda and must be captured in a way that allows it to be readily referenced and acted upon by AZ
- Information provided to the advisors must not exceed what is reasonably necessary to achieve the objectives of the advisory board and must be presented in a non promotional way
- Appropriate contracts and agreements must be in place with advisors
Consider these examples:
Example 1
This is an example of where the line between medical education and scientific exchange became blurred in the US leading to severe consequences for AstraZeneca:
In 2010 AstraZeneca in the US had to pay fines of $520 million to resolve allegations of off label promotion of Seroquel. The report stated that AstraZeneca
“promoted the unapproved uses by unduly influencing the content of, and speakers, in company sponsored continuing medical education programs. The company also engaged doctors to give promotional speaker programs on unapproved uses for Seroquel.”
Example 2
In the UK a complaint was made by Novo Nordisk about a symposium jointly sponsored by Bristol-Myers Squibb and AstraZeneca, at the Primary Care Diabetes Society (PCDS) conference entitled ‘The Kidney in Type 2 Diabetes: Victim or Target?’ Novo Nordisk said that the symposium promoted dapagliflozin (an SGLT-2 [sodium–glucose transporter-2] inhibitor) before the granting of a marketing authorization.
In particular, they alleged that the attendance at the symposium of sales representatives from Bristol-Myers Squibb implied that the event was promotional.
Ruling
On investigation the Panel considered that there was no evidence to show that the sponsors’ sales representatives attended the meeting; conversely the briefing material clearly showed that they were instructed not to attend. The Panel ruled no breach of the UK Code.
Example 3
In the UK a clinician complained about a series of advisory boards that he had been invited to by Astellas Pharma. When he attended one meeting he felt that the meeting was promoting the product Mycamine (micafungin) – there were too many presentations. After the meeting he was visited by an Astellas representative who had a document with his name on it. When he insisted on seeing the document he discovered that it contained details of the advisory board attendees, including what they thought about Mycamine and whether their opinions on Mycamine had been changed by the meeting.
On investigation the Authority found that this had been one of three pairs of regional meetings, with 12 advisors planned to attend from each region. Astellas said their purpose was to seek guidance and support in the future development and marketing of Mycamine. The company wanted to understand local issues and work on better management solutions.
The meetings started at 08:45 and ended at 16:30. Each had approximately 5 hours of presentations with 30 minutes allocated for discussion and feedback. The rest of the time was for refreshments.
Advisors were selected for invitation on the basis of recommendations from sales personnel. In their instructions it said that nominees had to have a belief in Mycamine, a sphere of influence including drugs and therapeutics, previous experience in getting drugs onto a formulary and a desire to work with Astellas and become a brand advocate.
Which of the following do you agree with?
- The agenda for the advisory boards is a cause for concern you need to consider whether the balance between time spent on one-way presentations and time for gathering feedback and advice is acceptable. In AstraZeneca’s view input from advisors should form the majority of the agenda.
- Sales personnel cannot recommend advisory board attendees sales personnel may have valuable insight into the details of their customers’ research interests for example. But they should not be recommending advisors on the basis of their prescribing habits or advocacy of a particular product. It should be on whether they have the required expertise to make a meaningful contribution to the advisory board.
- The document about the opinions of the advisory board members suggests the intention of the meeting was promotional The Panel considered that this was the development of brand advocates under the guise of an advisory board.
- The purpose of the meeting as stated by Astellas is not acceptable the Panel felt that the objectives were not necessarily unacceptable
Ruling
The Panel considered that the overall arrangements, particularly the development of brand advocates under the guise of an advisory board, brought discredit upon and reduced confidence in the pharmaceutical industry and in that regard ruled a breach of the UK Code.
Example 4
In the UK Pfizer complained about a Daiichi-Sankyo satellite symposium held at the Pharmacy Management National Forum, entitled ‘Financial and Policy Planning in Partnership with the NHS - A New Oral Treatment for the prevention of stroke in atrial fibrillation (AF) and treatment and secondary prevention of venous thromboembolism (VTE) in 2015 - Advance Budgetary Notification’
The new oral treatment at issue was edoxaban, an anticoagulant that was expected to be available 6 weeks after the symposium.
The symposium was advertised along with a synopsis on the Forum’s website which was publicly accessible. Pfizer said that this was promoting edoxaban before the granting of a marketing authorisation.
To register for the symposium delegates had to self-certify that advance budgetary notification content was relevant and appropriate to their role. Pfizer was concerned about the group nature of the advance budgetary notification because attendees would be from across the UK. The advance budgetary notification discussion should be about the significant budgetary impact locally for a payer. Everyone’s budget would be impacted differently. Pfizer also questioned whether there was adequate time to influence the budget with only 6 weeks notice.
On investigation the Authority found out that each satellite symposium lasted 40 minutes. The first 20 minutes consisted of two presentations; one from the regional business director (10 minutes) and one from a medical science liaison representative (MSL) for 10 minutes. Together the two speakers had 38 slides. The final 20 minutes of the symposium was for 1:1 individualised discussion around the local budget impact using a cost model.
Which of the following do you agree with?
- The publication of the synopsis on an open access website would constitute pre-licence promotion
- 6 weeks notice of a new launch is too short for payers
- Self certification of a payer role to gain entry may not be sufficient
- The widespread notification of the meeting is not approvable
- Using a symposium for advance notification is completely unacceptable
Ruling
The Panel considered that the notification and synopsis on the open access website constituted pre-licence promotion. They were critical of a symposium as a means to carry out advance notification and stated that the 20 minute time for a 1:1 discussion was unlikely to be enough for a delegate to fully understand the impact on their own budgets. They ruled that the company had brought discredit to the industry (that this was a very serious breach of the rules).
On appeal the ruling of pre-licence promotion was upheld. However he Appeal Board considered that the arrangements for ensuring that only payers attended the symposium were sufficient and that the company had not brought discredit to the industry.
