December 13, 2022

1. Funding Algorithms
December 13, 2022

2. Hot Topics Expert Webinar Series
www.cancertaintyforall.ca/ 2
pCPA and provincial listings | Wednesday Nov. 23, 2022 @1pm Eastern
Why timelines for public reimbursement of cancer medicines are getting longer and how this impacts patients
To register, please visit www.cancertaintyforall.ca/hot_topics
Funding algorithms | Tuesday Dec. 13, 2022 @1pm Eastern
What goes into decisions on what medicines patients can access across different lines of treatments?
QALYs | Tuesday Jan. 24, 2023 @1pm Eastern
How arbitrary decisions on cost-effectiveness impact patients’ access to some novel cancer treatments
Surrogate endpoints | Tuesday Feb. 21, 2023 @1pm Eastern
Are drug review processes flexible enough to expedite patients’ access to new cancer medicines?

3. Today’s panel
www.cancertaintyforall.ca/ 3
Speakers Moderator
Bill Dempster
CEO
3Sixty Public Affairs
Robert Bick
Consultant
(and CanCertainty
Campaign Co-Lead)
Alex Chambers
Manager
Rare Disease Patient Journey
Novartis Canada
Howard Lim
Medical Oncologist
BC Cancer Agency

4. www.cancertaintyforall.ca/ 4
Send in your questions!
• We will address your
questions in the last 15
minutes of the webinar
• Click on the “Chat” panel /
button any time to submit
your questions
• If it is addressed to one of
the panelists in particular,
please say who

5. Funding algorithm development
• CADTH develops funding algorithms that determine place of therapy
of cancer treatments on public drug plan formularies
- Indicates how new therapy could be used compared to existing funded
treatments and the impact on the sequence of use for other existing
funded therapies
- Intended to support provincial decision-making for drug reimbursement
• Previously, the Cancer Drug Implementation Advisory Committee
(CDIAC) played this role, until July 2019, when this mandate was
transferred to pCODR/CADTH
www.cancertaintyforall.ca/ 5
Source: CADTH website: https://www.cadth.ca/news/path-forward-integrating-key-functions-cancer-drug-implementation-advisory-committee-cdiac

6. Previous algorithm process
Process
The Canadian Association of Provincial Cancer Agencies (CAPCA) through CDIAC
represented payers, and provided advice concerning how new drugs could be
integrated into existing funding algorithms to achieve greater consistency
www.cancertaintyforall.ca/ 6
Issues
- Various stakeholders were concerned that CAPCA oversight of the Algorithm Development process
could result in economic information having greater “weight” than clinical information when
determining the drug sequencing algorithm
- The CDIAC process did not include broader clinician engagement (outside of clinical leads of
provincial tumour sites)
- Process lacked transparency - work product was tightly held, with no opportunity to comment on
or view a provisional algorithm

7. Current algorithm process
Improvements:
1. Explicit consideration of clinical evidence
2. Allows Manufacturer/Clinician/Patient Input
3. “Panel algorithm process” includes Implementation
panel with 3-5 cancer specialists, recognized as experts
for that specific tumour site
4. (Some) increased transparency: draft algorithm
published for feedback
www.cancertaintyforall.ca/ 7

8. www.cancertaintyforall.ca/ 8
A panel algorithm is undertaken when
advice of clinical specialists is required
to adapt an existing funding algorithm
or establish a new provisional funding
algorithm
 Typically be initiated when 1 or
more drugs may be impacted by the
implementation of a new drug
A rapid algorithm is undertaken when
pERC recommendations can be directly
incorporated into an algorithm without
supplemental advice from clinical
specialists
 Typically initiated in situations
where the new drug will not alter
the current sequence of drugs

9. Panel algorithm
Scoping Document
• Stakeholders are notified of an implementation advice panel being convened re:
sequencing of treatments for a particular indication
• CADTH posts a document detailing the scope of the implementation advice panel
and communicates that the call for stakeholder input is open
• Timeline: 10 business days to provide written input to CADTH on the treatment
algorithm and the place in therapy for product included in algorithm
Draft Provisional Algorithm Report
• Timeline: CADTH posts draft provisional algorithm report for stakeholder feedback
– call for feedback stays open for 5 business days
• CADTH reviews feedback with the chair of the implementation advice panel, who
determines if there is a need to reconvene the panel for additional meeting(s) to
discuss and revise the algorithm report
• Final report is posted on CADTH’s website
www.cancertaintyforall.ca/ 9

10. Rapid algorithm
 CADTH notifies stakeholders that a rapid algorithm is
being prepared by publishing project details on its website
www.cancertaintyforall.ca/ 10
Draft Provisional Algorithm Report
• Timeline: CADTH posts draft provisional algorithm report for stakeholder
feedback – call for feedback stays open for 5 business days
• Final report is posted on CADTH’s website

11. Templates
www.cancertaintyforall.ca/ 11

12. Patient Groups: Helping facilitate clinician input!
• Reach out to appropriate member of your Medical /
Scientific Advisory Group/Committee immediately
and seek to establish a “lead” clinician
• Be prepared to assist lead in assembling an ad hoc
group to participate in feedback
• Be prepared to assist in collecting Conflict of Interest
declarations from participating clinicians
• Assist lead author in adjudicating input from participating clinicians
• Assist in uploading Feedback on CADTH site
www.cancertaintyforall.ca/ 12
Tip: Timelines are tight…work quickly!
Input: Considerations for patient groups

13. Input: Considerations for patient groups (cont’d)
Recognizing that treatment guidelines are evidence-based products, patient
groups may want to mirror/endorse clinician input where possible
 Focus on preserving lines of therapy
and options within each line
 Provide ethical rationale for funding
therapy where appropriate
www.cancertaintyforall.ca/ 13

14. Input: Considerations for clinicians
You can do it alone, or you can participate in a Joint
Submission. Who do you join with?
• Are you part of a national research network for your disease
specialty/specialties?
• Are you a member of a patient group’s Medical/Scientific
Advisory Board?
• Are you a member of an expert clinician group that develops
consensus recommendations for the management and
treatment of a specific cancer?
• Were you an investigator for the clinical trial for the drug – and
are there other Canadian investigators?
www.cancertaintyforall.ca/ 14
Tip: Reach out also to the representative patient group (E.D. or CEO), as they often
assist in organizing the teams of clinicians to provide “joint” clinician input

15. Algorithm considerations
1. Current state: What is available (reimbursed) in each line of therapy, for what
cohorts of patients, and what are the sequencing
opportunities/combinations?
2. Near Future State:
• How will the drug under review disrupt or alter the current state?
• Will it impact access in subsequent lines? For instance, will evidentiary
limitations or pragmatic considerations regarding the new drug serve to
cut off access to subsequent lines of therapy?
• Would a physician potentially not prescribe this therapy because of future
access considerations?
3. Emerging evidence on sequencing: You may possibly be aware of emerging
evidence (e.g., abstracts, ongoing trials, patient registry RWE, ESMO E-learning
etc.) that is not part of the evidence package being considered by CADTH
www.cancertaintyforall.ca/ 15

16. Algorithm considerations (cont’d…)
4. Clinician Expert Opinion: You may have rationale supporting certain drug sequences despite the
lack of specific RCT evidence for that sequence:
• The drug under review has a similar mechanism of action as another drug currently
approved in that specific line of therapy
• There may be evidence related to another tumor site demonstrating the efficacy of that
sequence
5. Drug Pipeline: Are there other drugs in the pipeline for this tumour site? How will those drugs
disrupt or impact existing treatment pathways? If the standard of care for a preceding line of
therapy is likely to change in the future, how will that impact access to the drug currently under
review?
6. Real World Patients: You may know of evidence or have a sound clinical rationale for
recommending eligibility for the new drug beyond the study population
www.cancertaintyforall.ca/ 16

17. Dimensions of algorithm consideration:
Preserving lines of therapy
Expert physician opinion is “evidence”. If a sequencing proposition is
not in the current package of evidence being considered by CADTH, and
the proposition is not presented in any way, the final treatment
algorithm may not meet real world clinical needs.
www.cancertaintyforall.ca/ 17
Note: Advice provided within the provisional funding
algorithms is non-binding for the participating jurisdictions

18. Improvements to CADTH’s algorithm process
www.cancertaintyforall.ca/ 18
Stakeholders should urge CADTH
to reform the algorithm process to ensure:
1. It does not further delay reimbursement of Health Canada
approved treatments
2. That greater transparency be built into the provisional
algorithm development process in alignment with
CADTH’s Guiding Principles
3. Others for discussion… and, for now, a case study!

19. Case Study: Lenvatinib for Hepatocellular
Carcinoma (HCC)
• Sorafenib (SOR) was the standard of care in the 1st line treatment of metastatic HCC
(funded in all provinces)
• Lenvatinib is an oral, multiple receptor TKI for the 1st line treatment of adult patients with
unresectable HCC
o Lenvatinib demonstrated non-inferiority to sorafenib on OS and statistically significant and clinically
meaningful improvements in the secondary endpoints of PFS, TTP and ORR (REFLECT)
o It was widely expected to replace SOR as standard of care
• A change in Standard of Care in the 1st line impacts all subsequent lines of therapy
• Clinicians providing input had to consider not just the clinical utility of the drug under
review, but the impact it would have on existing and emerging 2nd and 3rd line treatment
options
www.cancertaintyforall.ca/ 19

20. Lenvatinib for Hepatocellular Carcinoma:
excerpts from clinician input
3.4 Sequencing and Priority of Treatments
There are numerous phase 3 trials for HCC that will be reporting in the next 1-2 years, and the
understanding on how to sequence new drugs and drug combinations with existing therapies will be
evolving. There are a number of available options for second line therapy following either intolerance
to sorafenib or progressive disease (cabozantinib, regorafenib, ramicurumab). Although LEN and SOR
differ somewhat in their targets, there is no available data to suggest that current second-
line therapies would be less effective following LEN. We believe it would be
reasonable to use regorafenib or cabozantinib post Lenvatinib. All of the available
second line therapies, and likely future immunotherapies, have novel targets that differ from both SOR
and LEN. Both therapies should be available in the first-line setting, and patients
should have the opportunity to switch in case of severe side effects from one of
these drugs.
www.cancertaintyforall.ca/ 20

21. Lenvatinib for Hepatocellular Carcinoma:
excerpts from clinician input
Implementation Commentary:
• 1st line therapy should include the option of SOR or LEN. Consideration should be made for
patients switching therapies due to side effect difficulties in the absence of radiological
progression
• We believe it would be reasonable to treat patients with SOR after LEN. While most 2nd line trials
were post SOR, the recent data at ASCO showed that patients still received second line therapy post
LEN and had a median survival of 20 months. If they demonstrated a response to LEN, survival was
around 25 months. ……However, further trial data regarding sequencing and immunotherapy will
be released in 2019 which may change the sequencing question
• In the future, if cabozantinib is funded, it could be potentially used as a 3rd line TKI treatment
since the CELESTIAL trial included patients who had up to 2 lines of previous treatment as long as
one line was SOR
www.cancertaintyforall.ca/ 21

22. pCODR Final Clinical Guidance Report:
Lenvatinib for HCC
www.cancertaintyforall.ca/ 22
“Despite the lack of evidence, the CGP acknowledge that there is no rationale to suggest that
the efficacy of second line HCC treatments would be influenced by the first line therapy.”

23. www.cancertaintyforall.ca/ 23
Discussion

24. NEXT WEBINAR
www.cancertaintyforall.ca/ 24
QALYs| January 24, 2022 @1pm Eastern
How arbitrary decisions on cost-effectiveness
impact patients’ access to some novel cancer
treatments

25. Coalition Members
www.cancertaintyforall.ca/ 25