Are the Cost-Effectiveness Rules Used by Public Drug Plans Denying Coverage to Canadians with Rare Disorders? Nigel Rawson, PhD President, Eastlake Research Group Affiliated Scholar, Canadian Health Policy Institute Senior Fellow, Fraser Institute

Rare Disorders About 7,000 known rare disorders Approximately 1 in 12 Canadians are affected by a rare disorder Around 3 million individuals Many are children

Clarke, CMAJ, 2006 CDR recommendations Sept 2003 - Dec 2005 for 33 drugs; 6 for rare disorders CDR recommendation negative for 19/33 (58%) including all 6 rare disorder drugs (100%) Evidence of clinical benefit insignificant or difficult to assess “Should Canadian patients be denied access to potentially effective new treatments for formerly untreatable and serious diseases only because it is virtually impossible to evaluate the cost-effectiveness of those treatments using conventional criteria?” “Is the current approach to reviewing new drugs condemning the victims of rare diseases to death?”

Is ‘condemning’ too strong?

50-year-old with aHUS “I have an ultra-rare blood disease that leads to kidney failure. The only effective therapy is a drug approved by Health Canada but denied by the provincial public drug plans because of its high cost. This disease destroyed my own kidneys as well a transplanted kidney donated by my wife. The doctors won't allow another transplant unless I’m on this drug. What’s really frustrating is that my province refuses to approve this drug for transplants. So I must remain on dialysis.”   aHUS patients have a poor prognosis: 50% progress to end-stage renal disease and the mortality rate is up to 25%

Funding for rare-disease therapy under the microscope (Globe & Mail, Nov 2, 2009) Bonnie Cameron was a 32-year-old single mother featured in a story about patients with fatal pulmonary arterial hypertension (PAH) who have been forced by the province to give up life-sustaining multi-drug cocktails because there is not enough scientific evidence to support the treatment.

Methods CDR submissions with final recommendations for first applications for new indications at December 31, 2015 First submissions for different indications were included; few re-submissions for the same indication were not Indication was categorized as rare if estimated population prevalence was <1/10,000 Information: date, indication, disease rarity, recommendation Reasons for final recommendation examined for rare disorder drugs Examined type of Health Canada regulatory review (priority or standard) Reviewed provincial listing of rare disorder drugs

CDR recommendations, 2004-2015

CDR recommendations, 2004-2015

CDR positive recommendations, 2004-2009 and 2010-2015

Negative CDR recommendations for rare disorder drugs, 2004-2015 23/36 (64%) received a negative recommendation For 17/23 (74%), reasons were: Lack of a clinically relevant outcome (13; 57%) Insufficient evidence of cost-effectiveness or high cost (11; 48%) In addition, Lack of significant clinical benefit (5; 22%)

Health Canada regulatory review type for common and rare disorder drugs

Positive CDR recommendation rate by Health Canada review and drug types

Provincial listing rates for rare disorder drugs, by CDR recommendation

Overall provincial listing rates for rare disorder drugs

Pan-Canadian Pharmaceutical Alliance Impact difficult to assess: Only 8 rare disorder drugs had completed pCPA negotiations (4 with positive, 4 with negative CDR recommendation) For 6 others, pCPA decided not to negotiate (5 with negative, 1 with positive CDR recommendation) As noted in recent article,* the lower CDR positive recommendation rate for rare disorder drugs leads to lower provincial listings * Available on Canadian Health Policy Institute website

Caveat: Listing does not necessarily mean accessible Coverage in most provinces is mainly limited to seniors and social assistance recipients Premiums, deductibles and copayments are often barriers to access Access for most rare disorder drugs subject to extensive clinical criteria, which can be another barrier to access

Conclusions Although CDR positive recommendation rate for rare disorder drugs has improved since Clarke’s 0%, at 39% (35% for ultra-rare), it remains poor compared with 66% for common disorder drugs (2010-15 data) CDR continues to be focused on requiring large RCTs with hard outcomes; less emphasis placed on studies using surrogate outcomes or observational data CDR evaluation of medical need not consistent with Health Canada Lack of a more holistic approach to assessing the value of rare disorder drugs continues to limit access to potentially beneficial new treatments Continuing inconsistencies in provincial benefit listings

Final Remarks Many new expensive rare disorder drugs in the development pipeline Pressing need for federal and provincial governments To implement the Orphan Drug Regulatory Framework and CORD’s 20-point Rare Disease Strategy To develop coherent nationwide policies to ensure that rare disorder drugs are reviewed, approved and funded quickly and equitably Alternative: Canada will continue to ‘condemn’ sufferers of rare disorders