November 2, 2015
Mr. Brent Fraser
Vice-President of Pharmaceutical Reviews
Canadian Agency for Drugs and Technologies in Canada (CADTH)
865 Carling Avenue, Suite 600
Ottawa, Ontario K1S 5S8

Dear Mr. Fraser:
Re: Consultation response: CADTH Anti-VEGF Therapeutic Review Draft Science Report

On behalf of Canada’s Research-Based Pharmaceutical Companies (Rx&D) and the member companies of BIOTECanada, we are pleased to provide feedback on the Anti-VEGF Therapeutic Review Draft Science Report (“the Draft Science Report” or “the report”). Our comments are restricted to policy considerations associated with the Draft Science Report. We will not comment on specific elements of the review itself.

With respect to therapeutic reviews in general, Rx&D and BIOTECanada maintain the guiding principle that these reviews should help optimize drug therapy to ensure that the right drugs are prescribed and used appropriately to improve or maintain patient health outcomes. Directly relevant to the current consultation, we would further highlight the following review elements which we believe represent reasonable best practices:

Therapeutic review timelines should be such that they provide adequate time for consideration and contribution by stakeholders;
If including an analysis of unapproved indications of a given product, then clear rationale and criteria regarding the appropriateness of its inclusion in the review should be pre-defined in addition to any Health Canada warnings or contraindications being respected;
Cost-containment should not be the central or dominant thematic lens through which a therapeutic review is initiated or conducted; and
Therapeutic review draft analysis and recommendations should be presented in a manner that explains whether and how the various types of evidence and various stakeholder contributions have been addressed.
Inadequate timeline for stakeholder input
We commend CADTH for moving to a standardized consultation period of a minimum of 30 days for both CDR and pCODR policy submissions and process changes. However, the timeline for comment on the considerably more dense scientific material contained in the current 160-page scientific document (10 business days) is inadequate for due consideration, scientific evaluation, and meaningful stakeholder response.

As a consequence of this inadequate timeframe, there is a risk that the overall quality of stakeholder feedback for the current review could be less robust (and thus less useful to CADTH) than it otherwise would have been. We encourage CADTH to apply the new consultation standards from CDR and pCODR to the therapeutic review work stream, including both in terms of broader process consultations and opportunities to comment on technical documents related to an individual review.

Use of “off label” comparators
The industry acknowledges that, in some cases, it may be appropriate for Health Technology assessors or other public agencies to evaluate certain drugs off-label as a reflection of clinical practice. These assessments need to be grounded on appropriate criteria including existing approved products and other relevant regulatory information related to the class in question. However, in the current review it does not appear that any stakeholders other than CADTH’s member jurisdictions have had input into what those criteria might have been or how they would be applied in scoping the products under consideration.

We are concerned that the inclusion of unapproved products in the scope of a review may convey an unintended impression of clinical relevancy or legitimacy where such evidence is contrary to direction given by the Health Canada. It is crucial that Health Canada’s role as the nationally recognized evaluator of safety and efficacy be maintained and respected. CADTH has established a precedent in this case by not only including therapeutic comparators which are unapproved for the indication of interest, but comparators for which there are clear and unambiguous warnings against the same indication. Health Canada warnings or counter-indications should always be highlighted and respected under the therapeutic review process in the interests of patient safety and as
a reflection of the substantial independent regulatory review which lead to their being included in a product monograph.

There is no explanation provided in the Draft Science Report as to why the approved product monographs for the products with approved indications are all properly cited, while the product
monograph of the unapproved product – including its clear warnings against intravitreal use – is not. CADTH classifies the product as a “non-indicated” therapy, noting that it is “not approved for the
treatment of retinal conditions in Canada” but without any reference to the actual source product monograph document. This is a significant omission which, at a minimum, fails to offer an equivalent
standard of information for all selected products despite that information being readily available on a public basis.

Furthermore, the Draft Science Report contains statements that contradict Health Canada approved Product Monographs and appears to recommend actions that are associated with risks outlined in the product monographs.

“While not recommended in the product monographs, fractioning of vials of [two of the products] is possible in order to reduce drug costs1.”
1 Anti-VEGF Therapeutic Review Draft Science Report, p. 15

Cost-containment should not be the Report focus
It is important to separate the scientific and pharmacoeconomic elements of the therapeutic review from budget considerations of the payers who will make use of the ultimate recommendations. CADTH describes a therapeutic review as an evidence-based review of publicly available sources regarding a therapeutic category of drugs or a class of drugs in order to support drug listing and policy decisions, as well as encouraging the optimization of drug therapy. In order to properly inform decisions in an impartial manner, the content of a Science Report should be limited to scientific evidence. Budgetary or affordability considerations should be left to those parties with responsibility for making those policy decisions, i.e. public and private payers. Without this separation, there is risk of undue influence on the outcome of the review, and the recommendations flowing from the review.

The Draft Science Report features a significant level of budget impact considerations, for reasons which have not been made apparent. The separation of evidence evaluation and budget impact analysis is important to ensuring review quality and impartiality. It is critical to take reasonable steps to avoid a scientific analysis being shaped by any particular cost-control policy objective, as appears to take place within the current review.

With greater emphasis than in previous therapeutic reviews, CADTH appears to be considering the affordability, rather than the cost-effectiveness of a treatment. This approach includes, for example, a hypothetical extrapolation of one province’s reimbursement program onto the budget impact analysis of another province, matters not typically relevant to a review of scientific and clinical evidence, or even cost-effectiveness.

Rx&D and BIOTECanada are not in a position to provide feedback as to the quality of this budget impact analysis due to a lack of time associated with the short comment period. We would however note that this budget impact assessment does feature prominently in the Draft Science Report despite clear evidence from patients regarding the restrictive impacts of those policies.

Stakeholder input considered and explained
The industry has a number of concerns regarding the new therapeutic review framework used for theAnti-VEGF Review. Although we appreciate the opportunity to provide feedback on the new framework, we note that the changes to the framework have been applied prior to consultation. The rationale, objectives, or potential consequences of the changes adopted have yet to be explored in the same consultative manner CADTH has engaged in for other policy and process changes.

With regard to the Draft Science Report, the input of patients has been noted. Specifically highlighted are the perceived differences between therapies such as negative patient experiences with the
unapproved drugs included in the study and some unfortunate incidences of patients feeling compelled into using a particular unapproved therapy. We sincerely hope these factors directly related to the realworld use of products in this class will be taken into consideration in CDEC’s eventual deliberation and potential recommendations. Ultimately, patients will assess whether they feel their perspectives and contributions to the Review have been reflected in the conclusions of the report.

Unlike the current CDR process, it is not apparent from the revised therapeutic review framework that any manufacturer input to a Review will be considered by the expert committee. Within the CDR
process, all manufacturer input is forwarded to CDEC along with the reviewer’s responses to the manufacturer comments. If this is not currently the practice for therapeutic reviews, we would
recommend that that all stakeholder feedback (including manufacturer and associations) should be forwarded to the expert committee in its original form for consideration against other information
generated within any Review.

In light of the foregoing, we recommend that the Draft Science Report should be modified to:
Address the inconsistencies with Health Canada approved product monographs;
Remove budgetary and affordability content; and
Identify the input received to date and how it was integrated into the review.
Finally we submit that recommendations stemming from this should acknowledge and reflect the primacy of Health Canada’s authority to review the safety, efficacy, and quality of drug products in
Canada. Please do not hesitate to contact us should you have any questions about our feedback. Rx&D and BIOTECanada welcome the opportunity to expand on our comments on both the current
therapeutic review as well as the general framework, and we remain committed to working with CADTH on enhancing the transparency, conduct, and outputs of therapeutic reviews.


Russell Williams , President, Rx&D

Andrew Casey, President & CEO, BIOTECanada