In this issue’s column, the All Wales Medicines Strategy Group reviews the impact of changes to the appraisal process for medicines for rare diseases in Wales.

In September 2015 the All Wales Medicines Strategy Group (AWMSG) updated the policy for appraising medicines developed to treat rare diseases. Reviewing the impact of the changes shows that the number of orphan and ultra-orphan medicines (and equivalents) considered and recommended by AWMSG has increased. AWMSG’s new policy allows greater consideration of the views of clinical experts and patient organisations.

A rare disease is defined by the European Commission as one that affects five or less than five people  in 10,000 of the general population. The clinical and cost-effectiveness evidence for a medicine for a rare disease is often based on small numbers of patients which means the evidence is often associated with greater uncertainty than for other medicines. Medicines for rare diseases may also be associated with high costs due to the small numbers of patients that will be treated.

AWMSG acknowledges that the rarity of a disease is likely to affect the evidence available and the cost of the medicine, and appreciates the need for innovation and research to meet the clinical needs of patients with a rare disease. Patients with a rare disease should have the same opportunity to access medicines as other patients and equity of access is important.

The changes to the way AWMSG appraises medicines for rare diseases were:

• Including medicines with European Commission designated orphan status. The previous AWMSG policy only applied to medicines that were considered by AWMSG to be ultra-orphan medicines (a smaller, sub-set of orphan medicines)

• Including medicines that are not European Commission designated orphan medicines but are developed to treat diseases with a low prevalence in Wales, equivalent to an orphan medicine (≤ five-in-10,000) or an ultra-orphan medicine (≤ one-in-50,000). These are referred to here as orphan equivalent and ultra-orphan equivalent medicines

• Considering additional criteria when appraising medicines for rare diseases, to allow AWMSG to consider a wider societal perspective, when the cost per quality-adjusted life year is higher than the usually accepted thresholds

• Adding a stage in the appraisal process to strengthen the patient and clinician voice. A Clinician and Patient Involvement Group can be convened after a negative recommendation at the preliminary recommendation stage, to discuss in more detail the additional benefits of a medicine from the perspective of clinicians, patients and society

Medicines for Rare Diseases Appraised by AWMSG

Between September 2015-and-December 2017, AWMSG appraised 79 medicines. Of these, 20 (25 per cent) met the criteria for appraisal under the updated policy; 10 were orphan or equivalent and 10 were ultra-orphan or equivalent.

14 (70 per cent) of the 20 appraisals were for a medicine that would not have met the criteria to be considered under the previous AWMSG ultra-orphan policy. This was because they were either an orphan or orphan equivalent medicine (n = 10), or they treated a condition with a prevalence equivalent to an ultra-orphan medicine but were not designated as an orphan medicine (n = four).

Analysing the data for AWMSG appraisals between September 2015-and-December 2017 showed a high positive recommendation rate for all medicines appraised by AWMSG, whether a medicine was indicated for a rare or non-rare disease (see table below).

Patient Access Schemes

Patient access schemes (PAS) are intended to improve the cost-effectiveness of a medicine by offering a discount, rebate, or other variation from its list price. Of the 20 appraisals considered under the new policy during September 2015-to-December 2017, 15 (75 per cent) were associated with a PAS. AWMSG recommended all medicines used to treat a rare disease that were associated with a PAS.

Clinician and Patient Involvement Group Meetings

Five Clinician and Patient Involvement Group (CAPIG) meetings were convened between September 2015-and-December 2017. Of these, three had a positive recommendation from AWMSG and two were not recommended. Convening a CAPIG meeting added up to 11 weeks to the AWMSG appraisal process. Feedback from AWMSG members, clinicians, patient organisations, and applicant companies who attended the CAPIG meetings was favourable.

Impact of the New Policy

The number of medicines that could be considered by AWMSG under the updated policy increased. 12 medicines that were appraised and subsequently given a positive recommendation would not have been eligible for consideration under the previous AWMSG ultra-orphan policy. One medicine, which was not recommended by AWMSG twice before introducing the new policy was reappraised and recommended for use in NHS Wales.

The positive recommendation rate for medicines for rare diseases was high (90 per cent). This was the same as the positive recommendation rate for medicines not indicated for a rare disease. This contrasts with a previous analysis, conducted between 2002-and-2014, in which AWMSG recommended 20 (59 per cent) of 34 orphan medicines (including ultra-orphan medicines). There was a marked increase to a 100 per cent positive recommendation rate of orphan / orphan equivalent medicines (excluding ultra-orphan medicines) compared with 52 per cent in the previous analysis.

The positive recommendation rates for medicines considered to be ultra-orphan or ultra-orphan equivalent were higher (80 per cent and 73 per cent, respectively) after introducing the new policy.

Two medicines meeting the criteria to be considered as a medicine for rare diseases were not recommended by AWMSG. These early findings suggest that the new policy has increased access to medicines for rare diseases by allowing additional considerations, particularly when the incremental cost-effectiveness ratio is above the usually accepted threshold.

Three medicines recommended by AWMSG were subsequently superseded by published NICE advice. NICE made a positive recommendation for all three medicines.