Health Technology Assessment Process for Oncology Drugs: Impact of CADTH Changes on Public Payer Reimbursement Recommendations.

Public reimbursement systems face the challenge of balancing provision of needed treatments and the reality of limited resources. Canada has a complex system for drug approval and public reimbursement, with jurisdiction divided between the federal government and the provinces/territories. A pivotal role is that of health technology assessment (HTA), which relies primarily on health economic principles to analyze the value of drugs on a population health basis and make recommendations about public reimbursement. The Canadian Agency for Drugs and Technologies in Health (CADTH) provides recommendations to all provinces but Quebec. This article provides an overview of Canada's approval and public reimbursement pathway, including the role of HTA and the economic principles on which it relies. Starting in late 2020, CADTH reduced the cost per quality-adjusted life year (QALY) threshold, the metric relied upon in making recommendations to public payers. An analysis of all 56 oncology drug final recommendations issued from January 2020 to January 2022 was conducted and confirms this reduction in the cost per QALY threshold. As a result of this threshold reduction, recommendations to the provinces include, in a number of cases, substantially greater price reductions. The potential implications for successful price negotiation with the pan-Canadian Pharmaceutical Alliance (pCPA), the public negotiating body for the provinces, are discussed.

Examining the association between oncology drug clinical benefit and the time to public reimbursement.

BACKGROUND: We examined if oncology drug indications with high clinical benefit, as measured by the American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), received public reimbursement status faster than those with lower clinical benefit from the time of pan-Canadian Oncology Drug Review (pCODR) recommendation. METHODS: Oncology drug indications submitted to pCODR between July 2011 and October 2018 were examined. Included indications had a regulatory approval date, completed the pCODR review process, received a positive pCODR recommendation, and been funded by at least one province. Trials cited for clinical efficacy were used to determine the clinical benefit (per ASCO-VF and ESMO-MCBS) of drug indications. RESULTS: Eighty-four indications were identified, yielding 65 ASCO-VF and 50 ESMO-MCBS scores. The mean ASCO-VF and ESMO-MCBS scores were 44.9 (SD = 21.1) and 3.3 (SD = 1.0), respectively. The mean time to provincial reimbursement from pCODR recommendation was 13.2 months (SD = 9.3 months). Higher ASCO-VF and ESMO-MCBS scores had low correlation with shorter time to reimbursement, (ρ = -0.21) and (ρ = 0.24), respectively. In the multivariable analyses, ASCO-VF (p = 0.40) and ESMO-MCBS (p = 0.31) scores were not significantly associated with time to reimbursement. Province and year of pCODR recommendation were associated with time to reimbursement in both ASCO and ESMO models. CONCLUSIONS: Oncology drug indications with higher clinical benefit do not appear to be reimbursed faster than those with low clinical benefit. This suggests the need to prioritize oncology drug indications based on clinical benefit to ensure quicker access to oncology drugs with the greatest benefits.

Comparing Manufacturer Submitted and Pan-Canadian Oncology Drug Review Reanalysed Incremental Cost-Effectiveness Ratios for Novel Oncology Drugs.

BACKGROUND: To determine the magnitude of difference between manufacturer-submitted and pan-Canadian Oncology Drug Review (pCODR) calculated incremental cost-effectiveness ratios (ICERs), incremental cost (ΔC), and incremental effectiveness (ΔE); to examine whether there is a significant difference in the proportion of ICERs deemed cost-effective; to evaluate trends in the ICERs over time; and to identify methodological issues in manufacturer-submitted economic models. METHODS: Economic guidance reports for all drug indications submitted from July 2011-November 2018 were extracted from the pCODR database. Cumulative distribution plots were constructed to compare the manufacturer-submitted economic values with both the pCODR lower- and upper-reanalyzed estimates. The proportion of drug reviews considered cost-effective at varying willingness-to-pay (WTP) thresholds by the manufacturer and pCODR were calculated. Manufacturer changes in ICERs over time from 2012 to 2018 were determined. Recurring methodological issues with manufacturer submissions were tallied. RESULTS: There were 73 unique indications that were included. Manufacturer-submitted ICERs were consistently lower than pCODR estimates for most indications. Manufacturer-submitted ICERs were generally more cost-effective over a range of WTP thresholds. From 2012 to 2018, manufacturer and economic guidance panel (EGP) lower limit reanalyzed ICERs did not change significantly over time. However, EGP upper limit re-analyses did show decreasing cost-effectiveness (increasing ICERs). The two most common issues identified in the manufacturer-submitted models were related to survival time horizon and utility estimates. CONCLUSIONS: Manufacturers tend to overestimate the cost-effectiveness of their therapies when submitting economic models to pCODR. Although certain methodological issues are still common in manufacturer-submitted models, revision rates are high for most issues raised by pCODR.

Reimbursement recommendations for cancer drugs supported by phase II evidence in Canada.

Background: Phase ii data are increasingly being used as primary evidence for public reimbursement for oncologic drugs. We compared the frequency of reimbursement recommendations for phase ii and phase iii submissions and assessed for variables associated with a positive or conditional recommendation. Methods: We identified submissions made to the pan-Canadian Oncology Drug Review's Expert Review Committee (perc), of the Canadian Agency for Drugs and Technologies in Health, July 2011 to July 2019, that were supported only by phase ii data. We identified variables within the perc's deliberative framework, including clinical and economic factors, associated with the final reimbursement recommendation. We conducted a multivariable analysis with logistic regression for these variables: feasibility of phase iii study, hematologic indication, and unmet need. Results: We identified 139 submissions with a perc final recommendation. In 27 instances (19%), the submission had only phase ii evidence, and a positive recommendation was issued for 63% of them (the positive recommendation rate was 82% for submissions with phase iii evidence). Clinical benefit (p < 0.001), unmet need (p = 0.047), and patient alignment (p = 0.015) were associated with a positive recommendation. If a future phase iii study was deemed feasible for submissions with only phase ii evidence, then in univariable (p = 0.040) and multivariable analysis (p = 0.024), the perc was less likely to recommend reimbursement (odds ratio: 0.132). Conclusions: Although more than half the oncologic submissions with phase ii data were recommended for public reimbursement, compared with submissions having phase iii data, they were less likely to be recommended. A positive or conditional recommendation was more likely if clinical benefit and alignment with patient values was demonstrated. The perc was less likely to recommend reimbursement for submissions with phase ii evidence if a phase iii trial was deemed possible.

Strategizing health technology assessment for containment of cancer drug costs in a universal health care system: Case of the pan-Canadian Oncology Drug Review.

A universal health care system has been a source of both identity and pride for Canadians for the last 6 decades. Currently, Canada actively negotiates the prices of cancer drugs but is not immune to their overwhelming financial toxicities. Prices of cancer drugs are set to ensure maximal profit based on what the market will bear rather than by the value they offer or solely because of the cost of research and development, as often is claimed by the manufacturers. The pan-Canadian Oncology Drug Review (pCODR) is mandated to provide funding recommendations to Canada's provinces and territories. For the most part, the pCODR has been crucial in assessing the cost-effectiveness and feasibility of new drugs in the Canadian context but it could assist more in safeguarding payers against extreme drug costs. Herein, the author suggests a few strategies by which national efforts such as the pCODR and its partners can help Canada to become a leader in facilitating value-based sustainable cancer care.

Conditional approval of cancer drugs in Canada: accountability and impact on public funding.

Background: We examined how conditional market approval of cancer pharmaceuticals by Health Canada (hc) affects public funding recommendations by the pan-Canadian Oncology Review (pcodr). We were also interested to see how often hc conditions are enforced. Methods: Health Canada and pcodr databases for 2010-2017 were analyzed for patterns in hc conditional authorization and post-authorization reviews of cancer drugs and for correlation with pcodr reimbursement recommendations. Results: Between 2010 and 2017, pcodr reviewed 105 unique drug-indication pairings; 21% (n = 22) had conditional hc authorization. In all cases, conditional authorization was given on the basis of preliminary data in a surrogate endpoint and was contingent on further data showing benefit in more robust outcome measures (for example, overall survival). Of those 22 drugs, 36% did not have updated data, 36% had updated data that met hc conditions, and 27% had data that met some, but not all, conditions. During the period considered, hc never revoked conditional authorization for failure to meet conditions. None of the 22 drugs was given an unconditional positive recommendation for public reimbursement by pcodr. A conditional recommendation was given to 11 of the drugs (50%), and reimbursement was not recommended for 6 drugs (27%) because of insufficient evidence. Conclusions: One fifth of the cancer drugs reviewed for public reimbursement in Canada were conditionally authorized by hc based on preliminary data. Conditional authorization was associated with a recommendation against public funding by pcodr. No drugs had their conditional market authorization revoked for failure to meet conditions, suggesting that a more robust hc reappraisal framework is needed.

The prioritization preferences of pan-Canadian Oncology Drug Review members and the Canadian public: a stated-preferences comparison.

The pan-Canadian Oncology Drug Review (pcodr) is responsible for making coverage recommendations to provincial and territorial drug plans about cancer drugs. Within the pcodr process, small groups of experts (including public representatives) consider the characteristics of each drug and make a funding recommendation. It is important to understand how the values and preferences of those decision-makers compare with the values and preferences of the citizens on whose behalf they are acting. In the present study, stated preference methods were used to elicit prioritization preferences from a representative sample of the Canadian public and a small convenience sample of pcodr committee members. The results suggested that neither group sought strictly to maximize quality-adjusted life year (qaly) gains and that they were willing to sacrifice some efficiency to prioritize particular patient characteristics. Both groups had a significant aversion to prioritizing older patients, patients in good pre-treatment health, and patients in poor post-treatment health. Those results are reassuring, in that they suggest that pcodr decision-maker preferences are consistent with those of the Canadian public, but they also imply that, like the larger public, decision-makers might value health gains to some patients more or less highly than the same gains to others. The implicit nature of pcodr decision criteria means that the acceptability or limits of such differential valuations are unclear. Likewise, there is no guidance as to which potential equity factors-for example, age, initial severity, and so on-are legitimate and which are not. More explicit guidance could improve the consistency and transparency of pcodr recommendations.

Challenges in striving to simultaneously achieve multiple resource allocation goals: the pan-Canadian Oncology Drug Review (pCODR) example.

The pan-Canadian Oncology Drug Review (pCODR) makes recommendations to Canada's provinces and territories (except Quebec) to guide their cancer drug funding decisions. The objective of this paper is to explore, using an economic perspective and the pCODR as an example, the challenges associated with striving to simultaneously achieve the goals of maximizing health benefits with available resources and improving access to a more consistent standard of care across Canada. The first challenge concerns how to interpret the goals in order to determine how resources should be allocated to achieve each goal. The second challenge relates to whether, if pursued simultaneously, both goals can be achieved to the same extent that each goal could have been achieved alone with the same available resources. Regarding the first challenge, we illustrate that, due to a lack of definitional clarity, it is difficult to determine exactly how resources should be allocated in order to achieve the goal of improving access to a more consistent standard of care across Canada. Regarding the second challenge, we illustrate that choosing to strive for both of the pCODR goals simultaneously will likely be associated with tradeoffs in the extent to which one or both goals can be achieved (relative to what could have been achieved for each goal alone with the same available resources). We suggest that, if the pCODR and the provincial drug plan decision-makers it supports want to strive for both goals simultaneously, they must prioritize the goals and explicitly identify the tradeoffs associated with the prioritization. This will ensure that the consequences of striving to simultaneously achieve both goals are explicit, transparent, and predictable for provincial drug plan decision-makers, physicians, patients, caregivers, and society as a whole.

Meaningful patient representation informing Canada's cancer drug funding decisions: views of patient representatives on the Pan-Canadian Oncology Drug Review.

In this interview with the patient representatives on the Expert Review Committee (perc) of the Pan-Canadian Oncology Drug Review (pcodr), those representatives offer their views about how to be a valuable contributing member of Canada's national cancer drug funding recommendation committee. The article seeks to inform readers, and especially clinicians, about pcodr from the perspective of the patient representatives.