Case studies

Challenge :

CADTH does not have an official WTP threshold for reimbursement decisions, but has been using $50,000/QALY to recommend price reductions for oncology drugs; the impact of these price reductions on time to access is unknown.

Methods :

A targeted review of the CADTH reimbursement reports for oncology drugs for 2020 and 2021 was conducted and for the drugs with positive reimbursement time to engagement and negotiation data was collected from the pCPA.

Obstacles :

CADTH’s definition of certain clinical benefit is not clear. Uncertainty in clinical benefit of new drugs is vaguely expressed in CADTH reports. We calculated clinical benefit using ESMO criteria from the clinical evidence of the reports and assessed correlation between clinical benefit and price reductions.

Impact :

The majority of the assessments reporting a price reduction recommended ≥70%, although CADTH acknowledged that these drugs had clinical benefit, also drugs with higher price reductions had longer negotiation times impacting  timely access.

Balijepalli C, Mynzhassarova A, Gullapalli L, Paul Roc N, Barakat S. Applicability of willingness to pay thresholds for oncology drugs: A review of submissions made to the Canadian Agency for Drugs and Technologies in Health. Value Health. 2022;25(7):S504. https://www.valueinhealthjournal.com/article/S1098-3015(22)01339-0/fulltext

Challenge :

There is a significant unmet treatment need in unresectable or metastatic melanoma patients that are resistant/ refractory to anti-PD-1 inhibitors. However, the size and characteristics of the population resistant to anti-PD-1s is not well known.

Methods :

A systematic literature review was conducted to identify the proportion of patients who are/become refractory/resistant to approved anti-PD-1 inhibitors in both the real-world setting and clinical trials.

Obstacles :

Resistance to anti-PD-1 therapies was not uniformly presented across studies. As such, we constructed definitions of resistance for each study by mapping within study data against the components of the consensus definition of resistance developed by the Society for Immunotherapy of Cancer (STIC).

Impact :

By identifying the proportion and clinical characteristics of patients who are/become refractory/resistant to approved anti-PD-1 inhibitors, it can help facilitate context for clinical activity for our clients, regulatory agencies, health technology assessment agencies, and payers.

Shui IM, Scherrer E, Frederickson A, Li JW, Mynzhassarova A, Druyts E, et al. Resistance to anti-PD1 therapies in patients with advanced melanoma: systematic literature review and application of the Society for Immunotherapy of Cancer Immunotherapy Resistance Taskforce anti-PD1 resistance definitions. Melanoma Res. 2022;32(6):393-404. https://journals.lww.com/melanomaresearch/Abstract/2022/12000/Resistance_to_anti_PD1_therapies_in_patients_with.1.aspx

Challenge :

There is a lack of pediatric safety studies observing neuropsychiatric outcomes of hydroxyzine, an antihistamine drug, in children. Combining this with its frequent use in infants and toddlers prompted an investigation into its safety.

Methods :

A population-based retrospective observational study was conducted using administration databases in Canada.

Obstacles :

Determining patterns of drug use and its effect on neuropsychiatric disorders. We conducted Cochran Armitage trend tests and logistic regression with generalized estimating equation models to describe the prescription trends and their association with mental and  neuropsychiatric disorders.

Impact :

Through identifying a association between extensive antihistamine drug use and the subsequent occurrence of neuropsychiatric disorders in children, it can help facilitate potential revisions to existing product monographs and clinical guidelines.

Gober HJ, Li KH, Yan K, Bailey AJ, Carleton BC. Hydroxyzine use in preschool children and its effect on neurodevelopment: A population-based longitudinal study. Front Psychiatry. 2022;12:721875. https://www.frontiersin.org/articles/10.3389/fpsyt.2021.721875/full

Challenge :

Pharmacogenetic testing involves identifying the impact of genetic variations on the efficacy and safety of drug therapy. The complexity of gene-drug interactions and variation in testing technologies can make it challenging to accurately model the clinical outcomes associated with different genotypes.

Methods :

A cost utility model was created to estimate the differences in the costs and the health-related quality of life between oncology patients who received pharmacogenetic testing to those that did not. A decision tree was created for pharmacogenetic testing and no testing pathways.

Obstacles :

Defining decision pathways between testing and no testing depending on genetic risk. Our solution was to utilize novel evidence methods through incorporating polygenic risk models in determining patient risk categories and expert elicitation to determine decision tree pathways for treatment.

Impact :

This study assessed the economic value of providing pharmacogenetic testing to pediatric oncology patients in Canada. Novel evidence methods were utilized in this study and can be tailored to assist other testing technologies in demonstrating value in their regulatory and reimbursement activities.

Yan K, Dionne F, Rassekh S, Ross C, Carleton B. Economic evaluation of pharmacogenomic testing in pediatric oncology patients treated with anthracyclines. Pediatr Blood Cancer. 2020;67:S441-S441. https://onlinelibrary.wiley.com/doi/10.1002/pbc.28742