5.0 The Sole Supply Decision – The decision making process

  1. The Sole Supply Decision was made by PHARMAC’s Board at its meeting on 29 March 2019. The documentation before the Board demonstrates that the March 2019 decision was the culmination of a decision making process that could be traced back at least 12 years to 2007.
  2. In order to properly understand the Sole Supply Decision, it is necessary to traverse the key steps in the decision making process. At the end of each section in the chronology of events that follows, and where it is appropriate to do so, I will add my own comments which will help elucidate the matters which I consider to be of particular significance to my findings.

2007 Neurological Subcommittee Meeting

  1. On 19 April 2007 the Neurological Subcommittee of PTAC met and undertook a Therapeutic Group Review of Antiepilepsy Drugs (AEDs). The Subcommittee’s Minutes record that the Subcommittee considered that “patients stabilised on one brand of lamotrigine should not switch brands”.[20]
  2. The Subcommittee also discussed the rules around ‘brand switching’ at the pharmacy level. The Subcommittee considered that it would be helpful if PHARMAC could clarify the rules around brand switching – and recommended that PHARMAC staff send out a reminder letter to prescribers explaining the substitution rules.[21]
  3. The Subcommittee’s Minutes were noted and accepted by PTAC, without further comment, at PTAC’s meeting in August 2007.

2009 Neurological Subcommittee meeting

  1. On 2 April 2009 the Neurological Subcommittee met and conducted a further Therapeutic Group Review of AEDs.
  2. While the Subcommittee’s Minutes do not record any specific discussion about lamotrigine, there is record of the Subcommittee’s consideration of a possible brand change of another AED, sodium valproate. The Subcommittee acknowledged the particular significance of reduced therapeutic benefit in patients with epilepsy – in particular because of the requirement in New Zealand that patients cannot drive for up to 12 months following a seizure. For this and other reasons the Subcommittee “was not supportive of any arrangement where patients with epilepsy stabilised on one brand of sodium valproate would be required to switch to a different brand”. The Subcommittee left the door open to the possibility of supporting an arrangement where there may be only one brand funded for new patients – provided certain safeguards were in place.[22]
  3. The Subcommittee’s Minutes were noted and accepted by PTAC, without further comment, at PTAC’s meeting in May 2009.
  4. It is clear to me that in April 2009 the Neurological Subcommittee was, at the least, cautious and conservative when it came to requiring stabilised patients to switch between brands of AED.

2010 Neurological Subcommittee meeting

  1. The Subcommittee considered AEDs again at its 5 August 2010 meeting. Although, again, referring to sodium valproate (rather than lamotrigine), the following entry in the Minutes is relevant:[23]

The Subcommittee expressed its concern around the high expenditure on sodium valproate and reiterated its previous comments that it would be supportive of an arrangement where a (cheaper) generic brand would be the only brand funded for new patients, providing that existing seizure-free patients with epilepsy could continue to access their current brand and that there was a period of time in which both brands would be funded for all patients in order for clinicians to become familiar with the new product. The Subcommittee also reiterated its view that the consequences of reduced therapeutic benefit in patients with epilepsy were substantial compared to some other disorders, in particular because of the requirement in New Zealand that patients cannot drive for up to 12 months following a seizure, meaning that the impact of even a single seizure can be significant for patients.

  1. The Minutes record PHARMAC staff having advised the Subcommittee that they were exploring different options for achieving savings in the epilepsy market.
  2. The Subcommittee’s Minutes were noted and accepted by PTAC, without further comment, at PTAC’s meeting in November 2010.
  3. The Subcommittee’s Minutes, and the consideration of these Minutes by PTAC, are a record of the on-going consideration that PHARMAC (including its committees) was giving to AEDs and the implications for moving to one funded brand. From the passage taken from the Minutes set out above, it is clear that the Subcommittee was open to the possibility of moving to one funded brand for new patients – provided safeguards were in place. Further, the Subcommittee was cognisant of the impact on patients – particularly because of the driving restrictions on those who suffer seizures.

2012 Neurological Subcommittee meeting

  1. At its meeting on 24 July 2012, the Subcommittee considered brand switching of AEDs. After referencing the medical literature, the Subcommittee noted that it considered “the risk of switching brands” to be “low”. Despite this, the Subcommittee considered that “insufficient evidence has been reviewed to date to establish the safety of brand switching for patients with epilepsy”.[24] The Subcommittee noted that there are potentially greater risks associated with switching between generic products compared with switching between the innovator brand and a generic brand.[25]
  2. The Subcommittee’s Minutes in relation to AED and brand switching were noted and accepted by PTAC, without further comment, at PTAC’s meeting in November 2012.
  3. It is clear that in 2012 the Subcommittee, and PTAC, continued to take a cautious and conservative approach.

2013 PTAC meeting

  1. At its meeting on 1 and 2 August 2013, PTAC reviewed a request for advice on the acceptability of switching from the innovator brand of sodium valproate to a generic sodium valproate. The Minutes record PTAC’s recommendation that generic sodium valproate should not be listed as ‘sole supply’ in the Pharmaceutical Schedule.[26]
  2. The Minutes record that it is Medsafe’s role to determine the safety, efficacy and bioequivalence of medicines. PTAC’s role was to consider suitability of sole supply.
  3. The important point for immediate purposes is that in 2013 PTAC gave careful and detailed consideration to the issues relating to brand switching of AEDs, and concluded, at that time, that mandatory switching would not be appropriate. PTAC’s Minutes record a detailed discussion, including traversing the medical literature and international standards, on the issues relevant to brand switching of AEDs.

2015 Neurological Subcommittee meeting

  1. On 11 November 2015, the Neurological Subcommittee met and considered the issue of brand switching of AEDs. This included, for the first time in any specific detail, brand switching of lamotrigine.[27]
  2. It is relevant to note that the Chair of the Neurological Subcommittee in November 2015, and at the meeting, was Professor Mark Weatherall. Prof. Weatherall was also a PTAC member – and subsequently chair of PTAC, a position he continues to hold.
  3. The Minutes record a detailed discussion and review of the medical literature. An analysis of the literature and the clinical studies and the, at times, differing conclusions reached, is beyond the scope of this review. However, it is worthy of note that, following its review of the published evidence that included systematic reviews regarding AED brand switching, the Subcommittee concluded that:[28]

in general, evidence from the randomised controlled trials did not appear to suggest that switching brands of AEDs has an effect on seizure frequency; however, some of the small non-experimental cohort studies reported high switch back rates and increase in health resources in patients who switched.

  1. For reasons that will become apparent, it is also worthy of note that the Subcommittee gave careful consideration to the AED categorisation system implemented in the United Kingdom by the Medicines & Healthcare products Regulatory Agency (MHRA).[29] The MHRA categorises AEDs to help healthcare professionals decide whether it is necessary to maintain a patient on a specific manufacturer’s product. Category 1 involves AEDs where the advice is to maintain the patient on a specific product. Category 2 involves AEDs where the need for continued supply on a particular product is a matter of clinical judgement for the prescriber and involves consultation with the patient and/or the carer. Category 3 relates to AEDs where it is “usually unnecessary” to ensure patients are maintained on a specific manufacturer’s product.
  2. In the UK, the MHRA places lamotrigine in ‘category 2’. Relevantly, the Neurological Subcommittee at its November 2015 meeting was unable to come to a consensus in relation to lamotrigine; and “whether it should be in category one or two, or in category two or three”.[30]
  3. Despite the lack of consensus on where lamotrigine fits within the UK categories, the Subcommittee reached some important conclusions at this meeting. It is clear from the Minutes that these were conclusions reached after careful consideration of the medical literature and other relevant standards – and were conclusions that came following consideration, over many years, of issues relating to brand switching of AEDs.
  4. The conclusions reached by the Subcommittee formed the basis of the Sole Supply Decision. The key conclusions warrant specific mention here. The Subcommittee:[31]
    1. considered that a managed brand switch to one brand of lamotrigine would be preferable to having multiple brands listed (as was currently the case);
    2. considered a competitive process for one brand (sole supply) of lamotrigine would be appropriate “provided that a suitable transition period was available”. The Subcommittee considered a transition period of 3-6 months would be required to support any brand switch. Where patients were unable to transition to a new brand for ‘exceptional clinical reasons’, patients could be considered through PHARMAC’s exceptional circumstances pathway;
    3. noted that patients are generally averse to change, and that if there is a managed brand switch, any change in seizure frequency could be perceived to have been caused by a change in brand;
    4. considered that there were no blood tests that would be useful to assist with monitoring a brand switch for lamotrigine;
    5. emphasised the importance of health professionals providing support and reassurance around brand changes and considered that the most important factor for maintaining epilepsy control was medication adherence;
    6. considered that GPs and pharmacists would be the health professionals most likely to be involved in supporting a brand change for lamotrigine (should this occur); and
    7. noted the New Zealand Transport Agency (NZTA) guidance that driving should cease if an individual is having seizures or has had a seizure in the last 12 months. The Subcommittee considered that if a patient were to have a seizure after a brand switch, their physician may be likely to report to the NZTA that they have had a change in brand of medicine by way of explanation. Therefore, the Subcommittee recommended that PHARMAC consult with the Chief Medical Officer of the NZTA should PHARMAC run a competitive process that could result in a managed brand switch for lamotrigine.
  1. PTAC considered the Neurological Subcommittee’s Minutes at its meeting on 11 & 12 February 2016. PTAC noted and accepted the Subcommittee’s Minutes without further comment on the possibility of moving to one brand of funded lamotrigine (PTAC commented on other issues raised in the Minutes).

May/June 2016 – PHARMAC’s correspondence with NZTA

  1. On 18 May 2016 PHARMAC wrote to NZTA, through its Chief Medical Advisor, noting the possibility of a managed brand change for some AEDs. PHARMAC provided NZTA with a hyperlink to the Neurological Subcommittee’s November 2015 Minutes. PHARMAC proposed a meeting between PHARMAC’s Medical Director and NZTA’s Chief Medical Advisor to discuss the issue.
  2. NZTA’s Chief Medical Advisor responded by way of letter dated 21 June 2016. The Chief Medical Advisor stated that he was not available to meet, but he provided the following advice to PHARMAC:

A change to the generic form of the same medication would be seen to be equivalent to a dose change and not a treatment change.

If the difference in bioavailability was thought to be insignificant, then no driving restrictions would be required. If it was thought to be significant then it would be the responsibility of the supplier to warn users of the risks of changing to the new medication, including the driving risks.

2016 Neurological Subcommittee meeting

  1. On 7 November 2016, the Neurological Subcommittee met and considered, amongst other things, PHARMAC’s plan to run a commercial process for one supplier of lamotrigine.
  2. In the briefing paper provided to the Subcommittee in advance of the meeting, members were reminded of the matters considered at the November 2015 meeting (and provided with a copy of the Minutes of that meeting); and PHARMAC reported to the Subcommittee on the correspondence with NZTA that had been initiated at the suggestion of the Subcommittee. The members were provided with copies of the letters with NZTA referred to above.
  3. PHARMAC’s briefing paper asked the Subcommittee to undertake a ‘therapeutic group review’ in four areas – one being AEDs. The general questions to the Subcommittee included whether the Subcommittee’s review revealed any particular areas of concern; whether there were any major developments internationally that PHARMAC staff should know about; and whether the Subcommittee had any additional comments relating the therapeutic group review.
  4. The Minutes for the Subcommittee’s meeting record the Subcommittee’s position that it could not perceive a problem with having different suppliers for the adult and paediatric strength preparations of lamotrigine tablets. The Minutes also note the correspondence between PHARMAC and NZTA (and record a subsequent meeting between PHARMAC and the NZTA Operations/Policy directorate). That is the extent of the matters recorded in the Minutes.
  5. The Neurological Subcommittee’s Minutes were considered by PTAC at its meeting on 9 and 10 February 2017. PTAC noted and accepted the Minutes with no comments made in relation to the proposal to move to one supplier of lamotrigine.
  6. It is clear that, by late 2016/early 2017, both the Neurological Subcommittee and PTAC were fully appraised of the steps PHARMAC was taking to run a commercial process for one supplier of lamotrigine. No concerns were raised.

2016 Mental Health Subcommittee meeting

  1. At the suggestion of the Neurological Subcommittee, the Mental Health Subcommittee of PTAC was asked to undertake a therapeutic group review of lamotrigine and sodium valproate. The reason for this was that these medications are commonly used for mood disorders (in addition to epilepsy).
  2. The Mental Health Subcommittee met on 23 November 2016. PHARMAC’s briefing paper to the Mental Health Subcommittee provided in advance of the meeting informed the Subcommittee about PHARMAC’s plans for running a commercial process that could result in only one brand of lamotrigine being funded. The Mental Health Subcommittee members were provided with the Neurological Subcommittee’s November 2015 Minutes. PHARMAC posed a number of questions to the Mental Health Subcommittee about the possible brand switch, the transition period, and implementation activities.
  3. The key conclusion reached by the Mental Health Subcommittee was that:[32]

it would not be clinically problematic from a mental health standpoint to switch patients from one brand to another if necessary (i.e. no more or less problematic than any other mood stabiliser brand change).

  1. Other comments made by the Mental Health Subcommittee included:
    1. Additional work would be required by pharmacists to reassure patients who were switched brands;
    2. Brand switching in the lamotrigine market already occurred, as there are multiple funded brands;
    3. A lamotrigine brand change in patients taking it for mental health indications would be unlikely to require additional clinic visits;
    4. A 3-6 month transitionary period appeared to be a sensible implementation timeframe from a mental health perspective;
    5. PHARMAC’s usual brand switch activities would be sufficient to support a lamotrigine brand change from a mental health perspective; and
    6. Because lamotrigine is in its own class amongst mood stabilisers, pharmacologically speaking, some patients may be particularly dependent on it psychologically and may need extra support.
  2. The Mental Health Subcommittee’s Minutes were considered by PTAC at its meeting on 9 and 10 February 2017. PTAC noted and accepted the Minutes with no comments made in relation to the proposal to move to one supplier of lamotrigine.
  3. It is clear that the Mental Health Committee was fully appraised of the steps PHARMAC was taking to run a commercial process for one supplier of lamotrigine. The Mental Health Committee did not regard the proposal as problematic – and made some useful comments about implementation.

June/July 2018 - Request for Proposals and Provisional Agreement with Mylan

  1. On 18 June 2018, PHARMAC issued a RFP for the supply of lamotrigine. The RFP noted that since the introduction of generic lamotrigine, PHARMAC had monitored the market and had sought clinical advice on lamotrigine. The RFP noted that the approximate annual expenditure on lamotrigine formulations was $10.2 million. PHARMAC stated that the purpose of the RFP was to obtain the best possible pricing to reduce the total expenditure and secure supply of adult and paediatric lamotrigine through one or two suppliers.
  2. PHARMAC’s Lamotrigine RFP Evaluation Committee selected the proposal submitted by Mylan as the preferred proposal for the supply of the adult presentations of lamotrigine. Mylan’s brand of lamotrigine is Logem. Mylan’s proposal would deliver savings over $30 million over a five year period.
  3. In an internal memorandum at the time, PHARMAC noted the following risks of proceeding with Mylan:
    1. 89% of patients (approximately 10,700 people) would be required to transition to Logem. While there are multiple brands currently listed, and some patients have switched treatments previously, this would be the first time PHARMAC would have implemented a sole supply approach in this market;
    2. There is a risk that if patients suffer adverse effects during the transition that this will be associated with the brand switch;
    3. GSK and Teva Pharma may withdraw their paediatric strength lamotrigine from the market; and
    4. For each month a decision is delayed, there would be a significant cost in potential savings lost.

August-September 2018 – Consultation process

  1. PHARMAC’s consultation document, setting out the proposal to move to one funded brand of lamotrigine 25 mg, 50 mg and 100 mg tablets (Logem), was released on 29 August 2018. The consultation document was published on PHARMAC’s website and was sent, by email, to subscribers to PHARMAC’s neurology and mental health distribution lists. It was also sent to PTAC and its relevant Subcommittees, pharmacies and clinicians involved in the treatment of epilepsy and mental health conditions, the Ministry of Health, DHBs, software vendors, suppliers, relevant consumer groups, and other interested parties. Respondents were given four weeks to comment on the proposal.
  2. The consultation document stated that there would be a three month transition period during which PHARMAC would reduce the subsidy for the other currently funded brands. If the suppliers of those brands did not reduce their price, patients were told that those patients using those brands would need to pay a manufacturer’s surcharge for their medicine or change to the fully-funded brand (Logem). After the three month transition period, the Arrow-Lamotrigine and Lamictal brands would be delisted, and patients would need to change to Logem to keep accessing funded lamotrigine. The consultation document stated that prescribers, pharmacists and patients would be supported with information and implementation activities to manage any change.
  3. The consultation document included hyperlinks that took readers to the clinical advice PHARMAC had received from the Neurological and Mental Health Subcommittees.
  4. PHARMAC received 32 responses to the consultation – including responses from consumers, health professionals, professional associations, suppliers and others. Generally speaking, consumers, consumer groups and suppliers expressed significant concerns; while health professionals and professional associations were supportive. It is not necessary to set out the different views in any detail here; however, a couple of examples are mentioned to illustrate the range of responses:
    1. Dr Charon Lessing, School of Population Health, University of Auckland, submitted in support of the proposal. Dr Lessing referred to her doctoral research into lamotrigine brand switching in New Zealand, and attached her published article on the topic. Dr Lessing’s submission noted that her research analysed 1,655 adult New Zealand patients over 12 months post brand switch, with key findings including:
      • Approximately one-quarter of patients using the originator brand of lamotrigine switched to generic lamotrigine within 60 days of the policy implementation in 2007.
      • For around 10% of those who switched brands, there were multiple switches (three or more) between generic and brand products.
      • Switch-back rates of 3% were apparent within 30 days post-switch.
      • There was no difference in health outcome measures associated with switching from originator lamotrigine to a generic equivalent.
    2. Consumers and consumers groups focussed on the risks seen with brand switching. The consumer submissions were genuine and heartfelt. By way of examples only:
      • “Now I face the horror of another change. I literally feel nauseous having just read about this…I really do appreciate how hard you all have to work to make things work but people will die…”
      • “In a community which talks to each other, we hear of other people for whom changing brands have triggered seizures.”
      • “As much as your ‘experts’ will go on about the bioequivalence being the same whatever the brand, you know full well that is not the case in reality because brand switches (of all types of drugs) have a long and clinically proven track record of affecting people individually and there is no guarantee that it won’t.”
      • One consumer noted, with concern, that the Neurological Subcommittee had not been able to reach a consensus on which (UK MHRA) category lamotrigine fits into – stating that “without a consensus on this issue people may potentially be given a generic form of medication which may not be suitable for and put them at risk of harm”. This consumer filed a lengthy submission that raised a number of relevant and important points – including about implementation activities.
  5. The submission made by Medsafe on the proposal warrants particular consideration here. The concerns raised by Medsafe have subsequently attracted media and other attention.

September – November 2018 - Medsafe submission and discussion

  1. Medsafe is the business unit within the Ministry of Health that is responsible for the regulation of medicines in New Zealand. Medsafe administers the Medicines Act 1981 and associated regulations – and, in doing so, it is Medsafe’s role to ensure that medicines meet acceptable standards of safety, quality and efficacy.[33]
  2. On 19 September 2018 Medsafe made a submission to PHARMAC on the proposal. In its opening paragraph, Medsafe set out its position in the following terms:

Medsafe considers that the proposal goes against the international consensus on switching between brands of anti-epileptic medicines. Medsafe also considers that this proposal poses a potentially significant safety issue. The international consensus [1] is that even with bioequivalent
anti-epileptic medicines, switching could result in the loss of seizure control for any individual using this medicine to control their epilepsy. A single seizure can be extremely detrimental to a patient’s life and all measures should be taken to ensure this risk is minimised. Consensus between international organisations and published literature is that any decision to change brands of AEDs should be made between the prescriber and the patient with approval from a specialist.

  1. Medsafe’s submission commented on specific matters, including the literature, referred to by the Neurological Subcommittee in its Minutes of its November 2015 meeting. Medsafe attached additional publications and studies which Medsafe considered were important.
  2. On 26 October 2018, PHARMAC announced that it was putting its proposal to move to one funded brand of lamotrigine on hold while it considered the submissions and sought further advice.
  3. On 13 November 2018, a senior group of PHARMAC representatives met with senior Medsafe representatives to discuss Medsafe’s submission. Minutes of the meeting were taken by PHARMAC, with a draft shared with Medsafe – and, in due course, Medsafe marked-up its proposed changes to the minutes.
  4. Following the meeting, Medsafe wrote to PHARMAC (by way of letter dated 21 November 2018) to clarify its earlier submission. Medsafe raised issues with one of the studies relied on by PHARMAC (Dr Lessing’s study, referred to above); and noted that the literature review that PHARMAC relied upon in support of the proposal was conducted three years’ previously. Medsafe recommended a further literature review be undertaken. Medsafe also made some recommendations about implementation (should the proposal proceed) – including that the brand switch should not occur when the patient reaches the pharmacy without prior counselling by the GP; and that GPs should refer the most vulnerable patients for specialist intervention to oversee and monitor the switch. Medsafe suggested that easy-to-read leaflets should be prepared and distributed by GPs, specialists and pharmacists – and all patients should be actively followed up to check that they were coping well with the change. Medsafe stated that PHARMAC should ensure that an alternative funding mechanism is made more accessible for patients who need to switch back to their original brand.
  5. There were other further exchanges between PHARMAC and Medsafe in December 2018 and January 2019. While there were some modifications to Medsafe’s position, Medsafe continued to have concerns and maintained its position that lamotrigine should be considered a Category 2 AED under the MHRA categorisation system.
  6. An important matter on which there was no disagreement between PHARMAC and Medsafe was that all generic brands of lamotrigine approved in New Zealand are all considered bioequivalent to the innovator, Lamictal.
  7. On 18 December 2018 PHARMAC informed Medsafe that, following Medsafe’s feedback and engagement, PHARMAC would be seeking clinical advice from the Neurological and Mental Health Subcommittee. Medsafe were told that the points it had raised would be brought to the Subcommittees’ attention; and that an updated literature search would be conducted.

February 2019 – Joint meeting of the Neurological and Mental Health Subcommittees

  1. On 7 February 2019 a joint meeting of the Neurological and Mental Health Subcommittees was held. The only agenda item for the two Subcommittees was to consider the proposal to switch to one funded brand of lamotrigine.[34]
  2. A briefing paper was sent to members on 18 January 2019. In accordance with PHARMAC’s usual practice, this gave the members three weekends to review the papers in advance of the meeting. The stated purposes of the briefing paper were to seek clinical advice on concerns that were raised during consultation; and to seek clinical advice on possible implementation activities to support the change (should it go ahead). The paper posed a number of questions for the Subcommittees, including the following questions which are central to this review:
    • Are the Subcommittee still comfortable with PHARMAC progressing with a move to one funded brand of lamotrigine, supported by the implementation activities noted in this paper and an exceptions mechanism?
    • Do the Subcommittees consider that a longer transition (i.e. longer than the previously advised 3-6 months) would be needed to support a brand change should the proposal go ahead?
    • Do the Subcommittees have any comments/suggestions regarding the proposed implementation activities noted in this paper?
  3. The briefing paper provided a comprehensive summary of the consultation feedback (including, but not limited to, Medsafe’s concerns, and the communications with Medsafe). A literature search was included, with studies and papers from over 50 publications summarised. A specific section included the publications provided by Medsafe. The paper provided the details of the research that had been undertaken by PHARMAC staff to ensure that all relevant publications were identified. Copies of the publications, consultation responses, and previous Subcommittee minutes were attached as appendices.
  4. The joint meeting was chaired by Professor Weatherall. There were three other PTAC members in attendance in their capacity as Subcommittee members – meaning that a total of four PTAC members attended. It was an in-person meeting, held in Wellington. The Minutes prepared for the meeting are extensive, and traverse the literature and the Subcommittees’ comments on the particular studies. The Subcommittees’ summary warrants being set out in full:[35]

1.45 The Subcommittee considered all of the consultation feedback, including the concerns raised by Medsafe with regards to the possibility of an increase in breakthrough seizures attributable to a brand change, and considered that based on a full review of the available evidence, there was no pharmacological reason to suggest there would be a clinical problem, with changing brands of lamotrigine for patients with epilepsy or mental health conditions.

1.46  The Subcommittee considered that there would be patients who experience adverse events, e.g. breakthrough seizures, even when there is no brand change. The Subcommittee considered that in the event of a brand change there would be patients who experience adverse events that would attribute these to a brand change, and that factors likely to contribute to this perception could include reduced adherence, nocebo, or other psychological factors.

1.47  The Subcommittee considered that ensuring adequate information, education, and reassurance to healthcare professionals and patients would be required to support patients with epilepsy or a mental health condition should there be a brand change for lamotrigine.

1.48  The Subcommittee considered that it was supportive of the proposal to move to one funded brand of lamotrigine (Logem), with implementation support as discussed above.

  1. It is evident to me from the documentation that I have reviewed that the joint meeting was comprehensive and substantive. All the concerns that had been raised about the proposal were carefully considered. The two Subcommittees’ support for the proposal was clear.

29 March 2019 – PHARMAC Board meeting

  1. PHARMAC’s Board considered the proposal to move to one funded brand of lamotrigine at its Board meeting on 29 March 2019.[36] The briefing paper to the Board noted that the proposal had not been dealt with by the Chief Executive under delegated authority because of the estimated financial impact of the proposal and because “the proposal is considered contentious due to perceived and potential clinical risks of a brand change in this population”.
  2. The briefing paper provided to the Board canvassed the process PHARMAC had undertaken, including setting out the concerns of Medsafe and other submitters – with the relevant documentation attached to the paper. Subcommittee Minutes were also attached; as was a proposed Implementation plan.
  3. The briefing paper proposed that implementation would occur over a five month period beginning on 1 May 2019. The Board was informed that, should the proposal be approved, it would mean significant savings of over $30 million over five years to DHBs.
  4. PHARMAC’s Board resolved to move to one funded brand of lamotrigine. The specific resolutions included approving the necessary changes to the Pharmaceutical Schedule; approving the provisional agreement with Mylan; and resolving that the consultation process on the proposal was appropriate and no further consultation was required. These resolutions comprised PHARMAC’s Sole Supply Decision.
  5. Professor Weatherall, the PTAC Chair, attended the Board meeting as an observer. As referred to above, Professor Weatherall had been closely involved in the process – including chairing the joint meeting of the Neurological and Mental Health Subcommittee meeting in February 2019.
  6. The Board’s Minutes also record that David Lui, the CAC Chair, attended the Board meeting as an observer. This is the first reference that I have seen in the documentation relating to PHARMAC’s decision making process to either Mr Lui, or the CAC. Further comment is made on this below.

Clinical Advisor’s advice

  1. This is an appropriate place to record the advice I have received from A/Prof Doogue on the decision to move to one funded brand of lamotrigine. As I have mentioned, A/Prof Doogue’s full advice is attached as Appendix 2.
  2. A/Prof Doogue’s key conclusions can be summarised here as follows:
    1. PHARMAC could reasonably conclude that for patients who take their medicines correctly, switching between brands of lamotrigine would not cause meaningful differences in drug exposure. PHARMAC could reasonably conclude the pharmacological effects of the brands would be the same.
    2. There were no material pharmacological risks with this brand change. The evidence that no pharmacological consequences were expected from the lamotrigine brand change “was stronger than for almost any other brand change”.
    3. PHARMAC had sufficient evidence to conclude that moving to one brand of lamotrigine was appropriate.
    4. The conclusions reached by the Neurological and Mental Health Subcommittees at the joint meeting on 7 February 2019 were consistent with, and supported by, the evidence relied on by A/Prof Doogue.
    5. A/Prof Doogue does not see any significance in the Neurological Subcommittee’s inability to reach a consensus as to whether lamotrigine should be in category 1, 2 or 3 of the UK’s MHRA categorisation.
    6. PHARMAC’s original ‘exceptional circumstances’ criteria was adequate protection for the particular consumer group.
  3. In the introduction to this report I referred to my discussions and correspondence with a paediatric neurologist. These took place in early May 2020, which was after I had submitted my draft report to PHARMAC. The paediatric neurologist raised concerns about the prescribing of generic lamotrigine and about PHARMAC’s implementation policies. After having read further, publicly available, documents relevant to the issue, some of the paediatric neurologist’s initial concerns were alleviated - but the paediatric neurologist continued to express concern as to whether Logem is therapeutically equivalent to the originator brand. The paediatric neurologist also raised concerns about what they regarded as a lack of systematic monitoring, amongst agencies, of treatment failures with generic medicines.
  4. I have discussed the paediatric neurologist’s concerns with A/Prof Doogue and he has reviewed the submissions made by the paediatric neurologist. A/Prof Doogue’s advice to me is that the matters raised by the paediatric neurologist do not change his earlier, written advice.

Footnotes

[20] Record of the Neurological Subcommittee of PTAC meeting, 19 April 2007, at [4.12].

[21] Record of the Neurological Subcommittee of PTAC meeting, 19 April 2007, at [4.13].

[22] Record of the Neurological Subcommittee of PTAC meeting, 2 April 2009, at [4.3].

[23] Record of the Neurological Subcommittee of PTAC meeting, 5 August 2010, at [5.2].

[24] Record of the Neurological Subcommittee of PTAC meeting, 24 July 2012, at [3.2].

[25] Record of the Neurological Subcommittee of PTAC meeting, 24 July 2012, at [3.3].

[26] Record of the PTAC meeting, 1 & 2 August 2013.

[27] Record of the Neurological Subcommittee of PTAC meeting, 11 November 2015.

[28] Record of the Neurological Subcommittee of PTAC meeting, 11 November 2015, at [7.7].

[29] Record of the Neurological Subcommittee of PTAC meeting, 11 November 2015, at [7.10].

[30] Record of the Neurological Subcommittee of PTAC meeting, 11 November 2015, at [7.12].

[31] Record of the Neurological Subcommittee of PTAC meeting, 11 November 2015, at [7.20] – [7.28]. 

[32] Record of the Mental Health Subcommittee meeting, 23 November 2016.

[33] See the ‘About Medsafe’ page on Medsafe’s website - https://www.medsafe.govt.nz/other/about.asp(external link)

[34] There was a second, unrelated agenda item for the Neurological Subcommittee only.

[35] Record of the Joint Neurological and Mental Health Subcommittee Meeting, 7 February 2019, at [1.45] – [1.48]. While the Minutes refer to ‘Subcommittee’ (in the singular), it is clear that the two Subcommittees were involved.

[36] The Board had been informed in May 2018 about the intention to initiate an RFP for lamotrigine. PHARMAC told me that the Board was updated on developments at each meeting leading up to the 29 March 2019 meeting.