This evaluation indicates that the CADTH-pCPA alignment has strengthened in recent years. Unlike the earlier analysis [3], no evidence was found that drugs for ultra-rare disorders had a greater probability of receiving a negative recommendation from CADTH. The few DRDs that received a negative recommendation generally did so because reviewers had concerns about efficacy. Their developers were unlikely to be invited to negotiate with the pCPA.
The majority of CADTH reviews resulted in a positive recommendation with clinical access conditions and/or a price reduction. CADTH’s clinical criteria have become more extensive, which may in part be due to more DRDs for specific gene mutations being launched. Price criteria commonly included a specific percentage reduction to achieve a cost-effectiveness threshold of $50,000 per QALY, which has apparently become CADTH’s standard. Price reduction recommendations range widely but were at least a 75% reduction for three-quarters of them.
Price recommendations to achieve a low $50,000 per QALY threshold are not restricted to DRDs. Similar recommendations can be found in reviews of drugs for common disorders. In fact, CADTH reimbursement reports have recently been restructured to require a pricing statement, despite the agency’s role not being price regulation. CADTH’s price recommendations are clearly intended to establish a starting point for pCPA negotiations. Nevertheless, a successful price negotiation was achieved for almost 90% of the DRDs with a positive recommendation. It seems unlikely that manufacturers submitted to price cuts of 75% or more.
Who benefits from the alignment between CADTH and the pCPA?
The alignment works well for the federal, provincial and territorial governments who own, fund and manage CADTH and the pCPA, as well as their own drug programs [6]. Government drug plans participating in a successful pCPA negotiation are not mandated to cover the medication. The likelihood that a DRD will be listed by most plans increased as time elapsed after a successful price negotiation but decreased as their cost increased. Delaying access means not having to pay for new listings. It also means manufacturers are hindered in selling their products and have less time to benefit from patent protection, while patients have to wait longer for access to potentially beneficial medicines.
The time taken by CADTH and the pCPA to complete their work resulted in access being delayed by more than a year for three-quarters of the DRDs and nearly three years for 25%. This on top of the time Health Canada takes to review and approve the DRDs for marketing (median 258 days, inter-quartile range: 210–357 days). Additional delays are caused by individual government drug plans deciding whether to list the DRDs. The entire process between marketing approval and government drug plan listing can take several years. For one DRD, sapropterin (Kuvan), it took almost 10 years since marketing approval to obtain a positive CADTH recommendation and complete a successful pCPA price negotiation [7] and the drug is still only listed in five government plans with restrictive access criteria.
Dates on which government drug plans decided to list the DRDs were not available for this analysis. However, a recent assessment of 63 medicines with an orphan drug designation approved by the European Medicines Agency between January 2015 and March 2020 demonstrated that the shortest median durations from Health Canada approval to reimbursement were 17.3 months in British Columbia and 19.6 months in Quebec and Manitoba, whereas in Europe, the shortest median durations from regulatory approval to a decision on reimbursement were 3.2 months in Austria, 4.1 months in Germany and 6.0 months in Finland [8]. It remains to be seen whether the work recently begun on a process to align regulatory reviews and health technology assessments in Canada reduces the duration between marketing approval and drug plan listing.
The current analysis also showed that, over the last eight years, clinical access criteria specified by CADTH have become more extensive and are applied rigorously by drug plans, which denies access for patients who do not satisfy the criteria [9]. Furthermore, higher cost DRDs were listed more slowly by drug plans, which especially impacts Canadians with ultra-rare disorders because drugs for these disorders tend to be more expensive.
Since 2017, Canada’s federal government has attempted to introduce major revisions in the regulations of the tribunal whose role is to prevent time-limited drug patents from being abused by excessive prices that would have significantly altered the country’s pharmaceutical environment [10]. This led to considerable uncertainty during the last five years in the biopharmaceutical industry and anxiety among patients, especially those wanting access to new ground-breaking medicines that offer solutions to unmet or poorly met health needs. Legal decisions against the federal government have led to a scale-back in the changes, which will be limited to an adjustment in the tribunal’s international list price comparison. Some but not all drug developers may accept this revision. Only time will tell whether DRDs are impacted more or less than other drugs by this change.
The government also intends to implement a national strategy for access to DRDs, but the affordability of DRDs has been over-emphasized so far [11]. High-cost ground-breaking DRDs that fulfill unmet needs for patients and also reduce expensive hospitalizations and other health services and are life-changing for patients but are unaffordable for the average Canadian must be part of the initiative. An urgent need exists for the federal, provincial and territorial governments to implement a long-overdue, comprehensive rare disease strategy [8, 12] that includes ensuring that DRDs are reviewed and reimbursed quickly and equitably to provide adequate health care to all Canadians that need them.