The Use of Off-label Comparators in NICE Appraisals An Indirect Endorsement?

Transcription

1 The Use of Off-label Comparators in NICE Appraisals An Indirect Endorsement? Jeanette Kusel 1, Grace Wong 1, James Hay 1, Laura Pettit 1 1 Costello Medical Consulting Ltd., Cambridge, UK

2 1. NICE. Guide to the methods of technology appraisal. June 2008 Background NICE have a remit to compare to routine care NICE therefore include interventions outside of their marketing authorisations as comparators Relevant comparators are identified, with consideration given specifically to routine and best practice in the NHS......Relevant comparator technologies may also include those that do not have a marketing authorisation for the indication defined in the scope but that are used routinely for the indication in the NHS. 1

3 Objective of study The objectives of this study were: To assess how frequently NICE request off-label comparators To determine the outcomes of the appraisals in which NICE requested off-label comparators To explore the implications of requesting offlabel comparators

4 Methods The NICE single technology appraisal (STA) scopes from were reviewed All STAs in development (as of 13/06/12) that had not been discontinued and had a draft or final scope were also reviewed Off-label comparators were identified as those that were being used outside their licence according to: The European Medicines Agency or The Electronic Medicines Compendium In cases where off-label comparators were requested in the scope, the manufacturer s submission, the Evidence Review Group report and the final NICE guidance were reviewed to ascertain the outcome of this request

5 Number of off-label comparators requested over time Number of scopes requesting an off-label comparator

6 Proportion of scopes with off-label comparators requested over time Proportion of scopes requesting an off-label comparator 45% 40% 35% 30% 25% 20% 15% 10% 5% 0%

7 Did the manufacturer perform the comparison to the off-label agent? Number of scopes requesting an off-label comparator (to June) Manufacturer did not perform the comparison Manufacturer did perform the comparison

8 Did NICE accept the decision not to compare to off-label agents? Number of scopes requesting an off-label comparator (to June) NICE rejected the decision NICE accepted the decision Off-label endorsement?

9 Did NICE accept the decision not to compare to off-label agents? Number of scopes requesting an off-label comparator (to June) NICE rejected the decision NICE accepted the decision

10 Case study eltrombopag (2010) TA205: Eltrombopag (Revolade ) for the treatment of chronic idiopathic (immune) thrombocytopenic purpura NICE requested a comparison against rituximab, which does not have a licence for this indication The manufacturer only supplied economic evidence for a scenario where rituximab came before eltrombopag in the treatment pathway When the ERG performed further analysis by placing eltrombopag as first in the sequence, before rituximab, it was found to be less cost-effective NICE rejected eltrombopag for this indication, thereby indirectly endorsing the use of off-label rituximab as firstline treatment in this indication

11 Case study belimumab (2012) ID416: Belimumab (Benlysta ) for the treatment of active autoantibody-positive systemic lupus erythematosus NICE requested that belimumab be compared to rituximab, which again does not have a marketing authorisation for this indication The manufacturer for belimumab did not perform this comparison, and the Final Appraisal Determination (FAD) committee rejected the new technology because of this The manufacturer then appealed against this decision The appeal was upheld in September 2012 and the conclusion was made that NICE s findings in relation to rituximab were not justified based on the lack of evidence for this agent in this indication

12 Off-label endorsement? Of the comparisons that were performed by the manufacturer, how many new interventions were rejected as being less cost-effective than the off-label comparator? Number of comparisons to off-label agents performed by the manufacturer (to June) New intervention rejected in favour of, or placed second-line to, an off-label intervention

13 Conclusions NICE have requested a substantial number of off-label comparators since 2008 There is an increasing number of scopes that request offlabel comparators over time, in line with the increasing number of appraisals undertaken by NICE When the manufacturer has not compared to the requested off-label comparator, NICE frequently (but not always) accepts this decision New interventions have been rejected by NICE in favour of off-label comparators Given the significant number of off-label comparators requested in ongoing appraisals, NICE will likely have to face similar issues in the future

14 Implications for NICE NICE must fulfil their remit of requesting comparators that are used as routine clinical practice However, when requesting off-label comparators, NICE may: Experience issues regarding lack of sufficient data Indirectly endorse the use of off-label interventions Open themselves up for liability Therefore what is required? A definition of what is considered routine practice Differentiation between routine practice and best practice A minimum requirement for data on the off-label comparator Consistency between appraisals

15 Thank you for listening Questions? Costello Medical Consulting Ltd (0)