Access to Oncology Medicines in Canada: Consensus Forum for Recommendations for Improvement^†

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript deals with the processes of incorporation of innovative medications for treatment of cancers in Canada, important issue in the context of public health. There are minor suggestions for improvement of the text:

[1] The title seems a little bit of the contents of the study, which presents very interesting results; thus, I suggest to include terms that may increase the appeal of the paper (e.g., Access to Oncology Medicines in Canada: Results of Consensus from the Forum for Recommendations for Improvement of Health Technology Assessment on Cancer Therapies”).

[2] The abstract includes a sentence that compromises the scientific aspects of the methods adopted in the study: “A modified Delphi methodology was used to confirm strong consensus on 30 questions involving five themes…”. The sentence seems to indicate that authors forced individuals to “confirm strong consensus”, i.e., mixing methods with results may support the interpretation that the study was biased. Therefore, it would be better to rewrite the sentence (e.g., “A modified Delphi methodology was used to identify potential consensus on 30 questions involving five themes…”).

[3] The abstract finishes indicating that “Clinicians expect urgent improvements in our health systems to give our patients their best chance of survival”, it would be better to indicate that the sentence refers to the Canadian health systems.

[4] Certain sentences in the beginning of the Introduction could be improved, e.g.:

·       Page 2, lines 55-56: “New treatments continue to improve survival for many cancers, but they are only beneficial if they can be [timely] accessed by patients”.

·       Page 2, lines 56-57: “For many years, most (but not all) new cancer treatments were [incorporated] to [the Canadian health system]”.

·       Page 2, lines 59-63: “However, the percentage of oncology medicines approved in the United States or the European Union coming to Canada steadily decreased from an average of 86% between 2006 and 2014 to only 50% in 2020 [2] when Patented Medicine Prices Review Board (PMPRB) reforms were proposed that would drastically reduce Canadian drug pricing [3-7].”. I suggest that the authors include an explanation on the role of PMPRB, and the reasons why the pressure to reduce drug prices decrease “the percentage of oncology medicines (…) coming to Canada”. It seems that maybe the pressure to reduce prices may compromise the acceptance of incorporation of certain medicines in part of Canadian provinces due to limits in public funding of cancer medication?

·       Page 2, lines 65-70: The sentence is very confusing, my suggestion is to rewrite in two sentences (i.e., “Health technology assessment (HTA) in Canada are performed through evaluation of the Institut national d’excellence en santé et en services sociaux (INESSS) for the province of Quebec [8] and the Canadian Institute for Drugs and Technologies in Health (CADTH) for the rest of Canada [9]. HTA reviews demand that technologies meet a low cost-effectiveness threshold of C$50,000 per quality-adjusted life year, an arbitrary value not adjusted for inflation since the 1980s [10].”. In addition, it would be interesting to apply inflation rates from 1980 until now to show how much 50,000 Canadian dollars represent nowadays. According to a brief search, the Consumer Prices Index from Canada accumulated from 1980 until 2022 is approximately 0.97, which corresponds to deflation in the period (i.e., reduction in prices), therefore, the argument that threshold should be revised due to inflation rates would not be reasonable. Maybe another argument based on changes in health outcomes, or changes in thresholds considered in other countries, could be better…

·       Page 2, line 78: It would be better to describe cancer treatment in technical terms (i.e., surgery, radiotherapy, and chemotherapy), instead of using “cut, burn and chemo”.

[5] The methods should include a description of the modifications included in the Delphi methodology (page 3); otherwise, readers may question the validity of the results of the panel.

[6] In addition, authors should indicate whether any of the background information gathered from participants comprised excluding criteria to participate in the panel (e.g., was there any criteria of knowledge, time in practice, etc. to be included in the panel?).

[7] The description of questions in the questionnaire only indicates that answers to certain questions were based on Likert scale; yet, other questions were based on multiple choice (e.g., questions 1.1, 1.9, and others, according to the Table 1). It would be interesting to indicate that in the description of the five themes of the questionnaire (page 3, lines 110-1280.

 

Finally, the results of the manuscript are very interesting, it would be important to emphasize the validity of the process adopted in the study to enhance HTA processes in other countries (i.e., include in the Discussion some remarks and comparisons on the HTA processes, transparency, and accountability in other countries, if possible).

Author Response

Please find it attached.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The motivation for the study, the methodology and results are well described. However, I am concerned the article is somewhat one-sided and fails to provide an honest account of what is going on.

 

It is uncontroversial that everyone wants a system where wealth should not be a factor in one's capacity to access the best available medicine, whether for cancer or any other disease. The fact that this is truer for clinicians working in oncology is not surprising. So in a way, the Delphi method is set up to discover the obvious, and it should not be surprising that the results presented in the tables weigh heavily towards "Strongly Agree" and "Agree".

 

The real challenge, which was not addressed in the survey, is what are we willing to trade-off to make this happen? The drivers of lack of access are many, but the delphi questions are designed in such a way that it seems the only problem is the unwillingness of payers to subsidise treatment, or their application of standards that are too strict. Clearly there are other drivers that are ignored, such as the profit motive that drives industry's business strategy, and the fact that as we develop drugs for more rare diseases, the costs of drug development per patient that may benefit is much higher. It would have been far more balanced if questions were asked about whether companies should be charging so much for medicines, or questions about responsible innovation e.g. Is there a price which is too high regardless of how effective the medicine is? - thinking of genetic therapies here.

 

According to IQVIA, it is anticipated that by 2027 over 50% of pharmaceutical spending in developed economies will be directed towards high-cost specialty drugs that only treat 2-3% of the population (

IQVIA. Global use of medicines 2023: outlook to 2027 https://www.iqvia.com/insights/the-iqvia-institute/reports/the-global-use-of-medicines-2023). This creates an inequity in its own right, and the proposal to be more lenient with both cost-effectiveness assessment and evidence assessment will only exacerbate this.

The authors also seem to conflate approval, subsidisation, and access. For instance they state on lines 367-371:

 

"Governments should take responsibility for explaining to their citizens why it takes so long to perform HTAs, why it can take many months for the pCPA to decide to negotiate prices for drugs with a reimbursement recommendation, why negotiations can take nearly a year [32], and why cancer therapies that other Canadians, Americans and Europeans can access are not available to them."

 

Canada, America, and Europeans have entirely different systems and they are not comparable in such a straightforward way. Drugs may be approved more quickly by the FDA, but that doesn't mean they are more affordable. Medicines may be approved more slowly in Canada, but once they are approved they may be more universally available. So such broad claims require contextualisation. Yes, drugs are approved more quickly in the United States, but that is because companies know they can negotiate the highest prices, and then strategically launch their products internationally using that as the precedent price. The United States also has a more fragmented insurance system so it is not clear how faster approval translates into affordable access.

 

Given the above, I suggest the authors include a limitations section or expand the discussion to make the overall presentation more balanced. At the very least:

 

1. Acknowledge the bias of the participants who clearly have an interest in wanting greater access to new cancer medicines regardless of expense. 
2. Acknowledge there are other factors that impede access which are not explored, such as a pharmaceutical companies constantly pushing the willingness to pay threshold to the limits in order to maximise profit. 
3. Acknowledge that access is complicated and not easily comparable across jurisdictions. While in some countries drugs may enter the market faster, they may not be as affordable to as many people.
4. Acknowledge that "equitable access" is open to interpretation. On the one hand we want to ensure the best drugs are available for use, but we also need to acknowledge there are limited funds that need to be distributed fairly across the entire population. The IQVIA statistics I provided above could be used.

 

Regarding the abstract:

 

The authors state that: "Canadian patients and their health care providers request improvements in timely access to life-saving therapeutics in line with other countries." However, patients weren't included in the delphi exercise so on what basis are they saying this?

 

I would also suggest the Abstract is amended to provide a more balanced account. The authors state that: "Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding." That is because these are the only questions that were explored. I'm sure they would be equally frustrated by pharmaceutical companies charging exorbitant amounts for drugs that often only provide marginal benefits as has been proven many times in the cancer context.

 

A minor point, Table 1 is busy and could be formatted better for easier reading. E.g. The questions and responses could use different fonts, and a small space between different questions would be helpful.

Author Response

Please find it attached.

Author Response File: Author Response.pdf