Aligned Reviews Between Health Canada (HC) and Health Technology Assessment Organizations (HTAs)
Date: September 26th, 2018
Time: 10:00 AM – 11:30 AM
Presenters: Alex Chambers (CADTH), Virginie Landreville (INESSS), M Coyer (HC), and T Richter (CADTH)
Purpose: To describe the HC-HTA (CADTH and INESSS) aligned review process in more detail, and discuss any questions regarding this initiative. This initiative aims to improve regulatory review in order to obtain more timely access to drug products.
- Background and Objectives
- Evolution of the Initiative
- Summary of the Process
- Information of Value to HTAs
- HTA Information Use
- Opportunities and Next Steps
- Questions and Answers
1) Background and Objectives
The purpose of this collaboration is to decrease the time between HC market authorization and HTA recommendations. This initiative is also in response to a call for greater review process coordination in order to facilitate faster public drug plan funding decisions.
Drug access continuum: focus on the first two players (HC and HTAs)
- HC – regulator of safety, efficacy and quality
- HTA partners – CADTH (CDR/pCODR) and INESSS, assess value
- pCPA – the price negotiator
- Federal/provincial/territorial Ministries of Health – the decision makers/funders
- From funding decisions being made months after HC authorization → reduced delays between Notice of Compliance (NOC) issuance and HTA recommendations
- From independent and sequential reviews → concurrent reviews
- From informal/ad hoc interactions → formalized sharing of information
- Decreased delays (dependant on timing of industry filing to HTAs)
- Improved communication (active discussions, efficient issue resolution, less duplication)
2) Evolution of the Initiative
- Late 2016 – idea for the pilot was developed
- 2017-2018 – success of the pilot from the Bureau of Metabolism, Oncology and Reproductive Sciences (BMORS)/ pan-Canadian Oncology Drug Review (pCODR)
- Reciprocal sharing (pCODR used to share info with BMORS, but not vice versa)
- Improved timing (open dialogue about timelines)
- Maintenance of timelines (e.g. changes in drug indication could be shared)
- Sharing of HC reports (e.g. pre-submission meeting info)
- Post-pilot – a formalized, transparent process was developed
- CADTH and INESSS changed their process, and began accepting submissions up to 180 days prior to anticipated NOC (includes oncology and non-oncology)
- HC/HTAs developed a Notice to Industry and a consent letter (posted June 2018)
- 5 submissions have undergone an aligned review since the pilot launch
3) Summary of the Process
- Scope – new drug submissions (NDS) and supplemental new drug submissions (SNDS) for new indications made to HC, where the sponsor intends to seek a coverage recommendation from the HTAs pre-NOC
- Applies to pharmaceutical and biologic drugs, including biosimilars
- Participation – aligned review participation is voluntary but encouraged
- Depends on submission of the consent template (cannot be changed in any way)
- Consent is submission specific, and needs to be filed with HC and/or up to 30 days after market authorization by HC
- Consent does not include information sharing between HTAs
- Timing – benefits will be maximized with earlier sponsor submission
- Strongly encouraged to give consent as early as possible and to file with the HTAs around the same time
- Requirements – independent review requirements will remain the same
- Transparency – sponsor participation in aligned reviews will be public
- Starting Fall 2018 (Oct 1st), HC will indicate the aligned submissions on the list
HTA Advance notification process: required for pre-NOC filing
- CADTH – manufacturers are required to submit an advanced notification template
- Features a section indicating willingness to participate in HC/CADTH info sharing
- Minimum notice of 30 business days for CDR and 120 calendar days for pCODR
- INESSS – manufacturers are required to notify INESSS of the intention to submit an evaluation request at least 2 months prior to planned submission
4) Information of Value to HTAs
- Wording of the indication, dosage range in the product monograph, dosage strengths that will be approved, dosage forms that will be approved and NOC/c qualifying studies
- Early notice of changes allows revisions of clinical/pharmacoeconomic reports
- Priority review or NOC/c eligibility assessment reports, pre-submission meeting minutes, proposed product monographs and final clinical review reports with manager’s memo
- Important for critical appraisal (internal validity of pivotal trials), clinical relevance of trial effect sizes and in interpreting the language used in approved indications
- Notification of a NOD (deficiency), NON (non-compliance) or timeline changes
- Requires for the CADTH review process and INESSS evaluation to be stopped
- Will decrease drain on resources since this process is very time consuming
- HTAs will not receive manufacturing process information included in a NON/NOD
5) HTA Information Use
- Information is received and transmitted using a secure distribution portal
- May share information with those who are included in the list of authorized recipients
- E.g. public drug plans, cancer agencies and the pCPA
- Shared information is stored in accordance with existing policies for storing confidential CADTH report information
- All information received from HC will be taken into consideration during the assessment
- INESSS may discuss submission with CADTH or HC upon receipt of the consent form
- Confidential info will be redacted from the final report prior to publishing
- Info is transmitted through a secure e-post platform
- Received information is stored according to current standard practices
- INESSS and CADTH recommendation issuance should not have > 1-month difference
6) Opportunities and Next Steps
- Impact of the alignment initiative will be measured, and the uptake rate will be monitored
- The process will be adjusted as needed to ensure it benefits HC, HTAs and industry, as well as to ensure it supports the goal of increasing collaboration
- Send any further follow-up questions to: OPPRS_enquiries@hc-sc.gc.ca, email@example.com, or firstname.lastname@example.org
7) Questions and Answers
- Are there plans for an aligned review process for medical devices?
- At this time there are no plans to expand the scope to include medical devices
- That would require a different group of people to respond to that
- Will take that idea back to those colleagues for their consideration
- Is there a targeted minimum delay for this process?
- Ideally it would be 0 days, but it is a voluntary process so it depends on when the submission comes in from the sponsor
- Smaller delays will be produced the earlier the submission comes in
- Is it possible that HC will inform the HTAs of a NOD/NON before manufacturers are aware?
- HTAs will likely be involved in the same discussion as the manufacturer if this were to occur, so it is likely not possible for the HTAs to be informed in advance
- Why can’t a pre-NOC be submitted prior than the timelines indicated?
- There is no value in submitting earlier than that since the minimum is 180 days
- If it is submitted too early then it will create a gap in the application
- What is included in the consent letter about specific information sharing?
- Provides consent to share between HC and CADTH, and HC and INESSS
- Existing consent to share information will not be changed
- Will the sponsor be made aware of comments between the federating bodies?
- Lots of interactions between HC and the HTA’s will occur, so the sponsor will not be advised of all of it due to the high volume of information being shared
- Does participation in the aligned pathway change the info that is shared downstream?
- May change since info that is usually requested downstream (by bodies such as CADTH and INESSS) could be integrated into the review process earlier in this agreement
- How can someone find out what kind of products are included?
- As of October 1st 2018, the submissions that have been accepted for aligned review will be identified on the HC list of submissions
- Does the sponsor have to agree to sharing of information with both HTAs?
- Yes as we want the benefits to apply to both HTAs, and not just CADTH or INESSS individually
- How will HTAs manage uncertainty over the aspects of the review that are finalized late in the process?
- There is always uncertainty with pre-NOC submissions, but this initiative will limit as much uncertainty as possible since the HTAs will be kept more up to date
- Does the alignment process have any effect on the PMPRB review?
- PMPRB is downstream from HC/HTAs, so they are not impacted by this project
- However they will be aware which products are undergoing aligned review (public info)
- What is the latest time frame for a sponsor to proceed with this aligned review?
- Consent is allowed to be received up to 30 days after the NOC is provided from HC
- What do adjusted timelines mean for performance dates?
- We will be exceeding or meeting the existing targets, the dates will not be pushed back
- Will CADTH and pCODR meetings be allowed before NOC is issued?
- There is no plan to change the current requirement of receiving the NOC document 6 days before the meeting
- Are there any targets for the percentage of HTA submissions that will undergo this pathway?
- At this point, the bar has not been set for goal percentages
- The first focus is on collecting the information regarding this new initiative
- WiIl industry have visibility for what info is being shared with further downstream groups?
- CADTH’s initial info sharing process will not be changed
- If HC info is incorporated into the publically shared information then downstream groups will have access to it as well (but the HC information will not be flagged as such)
- INESSS agrees that all the info will be fully integrated without indications for its source
- Do sponsors have a requirement to send NOD/NON info to HTAs?
- INESSS and CADTH both require notification of these decisions within 5 days of the sponsor receiving them
- It is in the best interest of the sponsor to share this info instead of relying on HC
- What is the experience in the pilot with sharing of info from CADTH to HC?
- Have not shared this info in any of the reviews to date
- CADTH and INESSS have recently announced an intention to collaborate with a panel of specialists. Are there any plans to further align with these bodies?
- No plans currently, but methods may developed in the future to become more efficient
- Are there plans to reduce the requirements for information submitted to HTAs since they will likely receive it from HC already?
- Requirements will remain the same
- Intent of this process is not to share the work, just share information
- Given that the CADTH process has several defined points for sponsor clarification, will HC adapt a similar process?
- Always looking to improve HC’s strategies, however we are not looking specifically at the CADTH process to guide these improvements
- What is the current experience of the timing of consent?
- With this more formalized alignment process, we have noticed that the consent forms are coming in very early in the process
- What does HC do with the info shared from CADTH?
- Not much info has been shared in this way yet, and it is usually just dates and timelines surrounding the submission
- Will HTAs still require copies of clarifaxes?
- Yes, as the existing requirements will remain the same
- Is there an optimal time to file a HTA submission?
- 180 days is the optimal time in order to minimize any gap in the assessment
- Does the alignment process apply to plasma products?
- Plasma products still maintain an independent review process, so it does not apply
- Will a summary of the HTA and HC discussion be included in the HTA report?
- No specific report will be provided for this separate information, but the discussion info can be incorporated in the existing HTA report
- HTA submission data may include longer term clinical data than is given to HC. Will this info be brought into the HC assessment?
- No this is not the intention, as the data packages are independent
- Would info sharing with CADTH and INESSS impact the HC label?
- Same as above, the processes remain independent
- With this new process, will sensitive information given to HC be shared and therefore accidentally publicly published?
- HTAs do not need this sensitive information, so it will not be shared with them
- Existing confidentiality guidelines will be maintained
- If a HC submission is also involved with another country (like Australia), will the information from the other country be shared with HTAs as well?
- The type of info that is being shared between countries right now is not the type that would be relevant for HTAs, but it is a possibility