Factors associated with positive and negative recommendations for cancer and non-cancer drugs for rare diseases in Canada

Abstract

Background In Canada, reimbursement recommendations on drugs for common and rare diseases are overseen by the Canadian Agency for Drugs and Technologies in Health (CADTH) and made through the pan-Canadian Oncology Drug Review (pCODR) and the Common Drug Review (CDR). While the agency specifies information requirements for the review of drug submissions, how that information is used by each process to formulate final reimbursement recommendations, particularly on drugs for rare diseases (DRDs) in which per patient treatment costs are often high, is unclear. The purpose of this study was to determine which factors contribute to recommendation type for DRDs. Methods Information was extracted from CDR and pCODR recommendations on drugs for diseases with a prevalence < 1 in 2000 from January 2012 to April 2018. Data were tabulated and multiple logistic regression was applied to explore the association between recommendation type and the following factors: condition/review process (cancer vs non-cancer), year, prevalence, clinical effectiveness (improvements in surrogate, clinical and patient reported outcomes), safety, quality of evidence (availability of comparative data, consistency between population in trial and indication, and bias), clinical need, treatment cost, and incremental cost-effective ratio (ICER). Two-way interactions were also explored. Results A total of 103 recommendations were included. Eleven were resubmissions, all of which received a positive recommendation. Among new submissions ( n = 92), DRDs that were safe or offered improvements in clinical or patient reported outcomes were more likely to receive positive reimbursement recommendations. No associations between recommendation type and daily treatment cost, cost-effectiveness, or condition (cancer or non-cancer) were found. Conclusions Clinical effectiveness, as opposed to economic considerations or whether the drug is indicated for cancer or non-cancer, determine the type of reimbursement recommendation.

Correlation between clinical trial endpoints of marketed cancer drugs and reimbursement decisions in China

“…Scholars are divided on drugs of uncertain clinical benefit, with some opposing the positive reimbursement decisions of drugs with unclear clinical benefits ( 21 ) and others advocating that a new standard for drugs with surrogate endpoints should be established ( 22 ). Previous studies have analyzed the relevance between reimbursement decisions and clinical trial endpoints ( 23 – 28 ), the situation is not consistent across countries, while few studies have focused on the situation in China.…”

A systematic literature review of revealed preferences of decision-makers for recommendations of cancer drugs in health technology assessment

“…The characteristics of the included studies were shown in Table 1. The majority of studies ( n = 7) (21–23;25–27;29) only investigated decisions in a single agency, except that Pinto et al (28) study researched the recommendations in two agencies in a separate analysis, and Maynou Pujolras and Cairns (24) study pooled the decisions from six European agencies. A total of six agencies were studied independently, including Pharmaceutical Benefits Advisory Committee (PBAC) in Australia (21), Commission of Reimbursement of Medicines (CRM) in Belgium (27), Health Insurance Review and Assessment Service (HIRA) in South Korea (22), National Authority for Health (HAS) in France (23), NICE in the UK (28), and pCODR in Canada (25;26;28;29).…”

“…The number of HTA decisions ranged from 17 to 393 (median = 75). Most studies ( n = 6) have no specific restrictions on the types of cancers with three exceptions that Li et al (23) study was limited to the solid cancers, Niraula and Nugent (26) study was limited to the solid cancers and hematologic malignancies, and Nagase et al (25) study was limited to the rare cancers. The definitions of explored factors and analysis methods were summarized in Supplementary Tables 2 and 3, respectively.…”

“…A total of 1,636 articles were excluded after the screening of title and abstract, and 119 articles were included for full-text evaluation. Finally, nine articles were included in the analysis (Figure 1) (21)(22)(23)(24)(25)(26)(27)(28)(29).…”

Assessment of the clinical and cost-effectiveness evidence in the reimbursement decisions of new cancer drugs

“…Previous studies have assessed possible influential factors on decision making and found, for example, the reported clinical benefit, level of severity, orphan designation status, study design, treatment intent, and the availability of alternative treatments to influence reimbursement decisions for cancer drugs and drugs in general. 26 , 28 , 31 , 32 , 33 , 34 Concerns regarding the quality of evidence and uncertainty when assessing clinical benefits and effectiveness used in cost-effectiveness analyses and reimbursement decisions have been emphasized. 35 , 36 , 37 Studies on the available evidence for cancer drugs have primarily assessed the evidence used for market authorizations and found that evidence for the clinical benefit is limited regarding the effects on patient-centered outcomes such as survival and QoL.…”