Assay-guided treatment sequencing in chronic lymphocytic leukemia (CLL): a cost-effectiveness analysis.

Costly targeted cancer treatments challenge publicly-funded healthcare systems seeking to align expected benefit with value for money. In 2021, The Canadian Agency for Drugs and Technologies in Health (CADTH) published a provisional funding algorithm for risk-based treatment of chronic lymphocytic leukemia (CLL). We estimate the cost-effectiveness of this algorithm against current standard of care. We constructed a probabilistic Markov model comparing next generation sequencing (NGS) assay-guided front-line treatment of acalabrutinib versus venetoclax with obinutuzumab to a comparator wherein patients initiate acalabrutinib. The primary outcome was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Analyses were conducted from the British Columbia healthcare system perspective, with outcomes discounted at 1.5%. Assay informed treatment for patients with CLL resulted in an incremental cost effectiveness ratio of $18,040 (95% CI $16,491-$19,501) per quality adjusted life-year (QALY) gained. The probability of the NGS guided treatment algorithm being cost effective was 80% at a willingness to pay threshold of $50,000 and a corresponding ICER of $18,040. Assay-guided treatment sequencing adds additional costs to healthcare but may be a cost-effective intervention for adult patients with CLL. Integration of real-world evidence would improve the validity and reliability of model estimated for decision-makers.

How health technology assessment can help to address challenges in drug repurposing: a conceptual framework.

Drug repurposing faces various challenges that can impede its success. We developed a framework outlining key challenges in drug repurposing to explore when and how health technology assessment (HTA) methods can address them. We identified 20 drug-repurposing challenges across the categories of data access, research and development, collaboration, business case, regulatory and legal challenges. Early incorporation of HTA methods, including literature review, empirical research, stakeholder consultation, health economic evaluation and uncertainty assessment, can help to address these challenges. HTA methods canassess the value proposition of repurposed drugs, inform further research and ultimately help to bring cost-effective repurposed drugs to patients.

Use of Efficiency Frontiers to Align Prices and Clinical Benefits of Biologic Therapies for Plaque Psoriasis.

Importance: The US lacks a systematic approach for aligning drug prices with clinical benefit, and traditional cost-effectiveness analysis (CEA) faces political obstacles. The efficiency frontier (EF) method offers policymakers an alternative approach. Objective: To assess how the EF approach could align prices and clinical benefits of biologic medications for plaque psoriasis and estimate price reductions in the US vs 4 peer countries: Australia, Canada, France, and Germany. Design and Setting: This health economic evaluation used the EF approach to compare the prices and clinical benefits of 11 biologics and 2 biosimilars for plaque psoriasis in the US, Australia, Canada, France, and Germany. Data were collected from February to March 2023 and analyzed from March to June 2023. Main Outcome Measures: EFs were constructed based on each biologic's efficacy, measured using the Psoriasis Area and Severity Index (PASI) 90 response rate, and annual treatment cost as of January 2023; US costs were net of estimated manufacturer rebates. Prices based on the EF were compared with traditional CEA-based prices calculated by the Institute for Clinical and Economic Review at a threshold of $150 000 per quality-adjusted life-year gained. Results: Among 13 biologics, PASI 90 response rates ranged from 17.9% (etanercept) to 71.6% (risankizumab); US net annual treatment costs ranged from $1664 (infliximab-dyyb) to $79 277 (risankizumab). The median (IQR) net annual treatment cost was higher in the US ($34 965 [$20 493-$48 942]) than prerebate costs in Australia ($9179 [$6691-$12 688]), Canada ($15 556 [$13 017-$16 112]), France ($9478 [$6637-$11 678]), and Germany ($13 829 [$13 231-$15 837]). The US EF included infliximab-dyyb (PASI 90: 57.4%; annual cost: $1664), ixekizumab (PASI 90: 70.8%; annual cost: $33 004), and risankizumab (PASI 90: 71.6%; annual cost: $79 277). US prices for psoriasis biologics would need to be reduced by a median (IQR) of 71% (31%-95%) to align with those estimated using the EF; the same approach would yield smaller price reductions in Canada (41% [6%-57%]), Australia (36% [0%-65%]), France (19% [0%-67%]), and Germany (11% [8%-26%]). Except for risankizumab, the EF-based prices were lower than the prices based on traditional CEA. Conclusions and Relevance: This economic evaluation showed that for plaque psoriasis biologics, using an EF approach to negotiate prices could lead to substantial price reductions and better align prices with clinical benefits. US policymakers might consider using EFs to achieve prices commensurate with comparative clinical benefits, particularly for drug classes with multiple therapeutic alternatives for which differences can be adequately summarized by a single outcome measurement.

Estimated Spending on Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa.

Importance: New gene therapies can offer substantial benefits to patients, particularly those with rare diseases who have few therapeutic options. In May 2023, the US Food and Drug Administration (FDA) approved the first topical gene therapy, beremagene geperpavec (B-VEC), for treating both autosomal recessive and autosomal dominant dystrophic epidermolysis bullosa (DEB). However, FDA approval was based on limited data in patients with autosomal dominant disease, even though they comprise approximately 50% of all DEB cases. Objective: To estimate projected spending in the US on B-VEC therapy for treating autosomal recessive and autosomal dominant DEB. Design, Setting, and Participants: This economic evaluation used data from the National Epidermolysis Bullosa Registry to estimate the current population of US patients with autosomal dominant and autosomal recessive DEB, with the aim of estimating US spending on B-VEC therapy from an all-payers perspective during 1- and 3-year periods after FDA approval. A base-case cost of $300 000 per patient per year was assumed based on a report from the manufacturer (Krystal Biotech). Exposure: Treatment with B-VEC. Main Outcomes and Measures: Estimated overall spending on B-VEC in the first year and over a 3-year period after FDA approval. Several prespecified sensitivity analyses with different assumptions about the eligible patient population and the cost of therapy were performed, and lifetime total costs of treatment per patient were estimated. Results: The estimated number of US patients with DEB who were eligible for treatment with B-VEC in the first year after FDA approval was 894. The estimated total expenditure for B-VEC therapy was $268 million (range, $179 million-$357 million). Over a 3-year period, estimated spending was $805 million (range, $537 million-$1.1 billion). Estimated lifetime total costs per patient were $15 million (range, $10 million-$20 million) per patient with autosomal recessive DEB and $17 million (range, $11 million-$22 million) for patients with autosomal dominant DEB. Conclusions and Relevance: Results of this economic evaluation suggest that the FDA's broad indication for the use of B-VEC in treating both autosomal recessive and autosomal dominant DEB will have significant implications for payers.

High Cost of Chimeric Antigen Receptor T-Cells: Challenges and Solutions.

Chimeric antigen receptor (CAR) T-cells are a cellular immunotherapy with remarkable efficacy in treating multiple hematologic malignancies but they are associated with extremely high prices that are, for many countries, prohibitively expensive. As their use increases both for hematologic malignancies and other indications, and large numbers of new cellular therapies are developed, novel approaches will be needed both to reduce the cost of therapy, and to pay for them. We review the many factors that lead to the high cost of CAR T-cells and offer proposals for reform.

Congress' Misguided Plan to Ban QALYs.

This Viewpoint discusses the flawed assumptions and potential negative impacts of a proposed federal bill that would ban government health care programs from using the quality-adjusted life-year (QALY) and "similar measures" when determining insurance coverage or negotiating prices.

Health technology assessment for cancer medicines across the G7 countries and Oceania: an international, cross-sectional study.

BACKGROUND: Criticisms have emerged that cancer medicines offer modest benefits at increasingly high prices. Reimbursement decisions made by health technology assessment (HTA) agencies have become a complex endeavour for cancer medicines. Most high-income countries (HICs) use HTA criteria to identify high-value medicines for reimbursement under public drug coverage plans. We compared HTA criteria specific for cancer medicines in economically similar HICs, to understand how these criteria contribute to reimbursement decisions. METHODS: We did an international, cross-sectional analysis in collaboration with author investigators across eight HICs, from the Group of Seven (known as G7; Canada, England, France, Germany, Italy, and Japan) and Oceania (Australia and New Zealand). Publicly available data from HTA agency reports and official documentation were extracted and analysed between Aug 15, 2021, and July 31, 2022. We collected data pertaining to the decision-making criteria used by the national HTA agency; HTA reimbursement status for 34 medicine-indication pairs corresponding to 15 unique US top-selling cancer medicines; and HTA reimbursement status for 18 cancer medicine-indication pairs (13 unique medicines) with minimal clinical benefit (score of 1 on the European Society of Medical Oncology Magnitude of Clinical Benefit Scale). Descriptive statistics were used to compare HTA decision criteria and drug reimbursement recommendations (or for Germany and Japan, final reimbursement status) across the eight countries. FINDINGS: Therapeutic impact related to clinical outcomes of the new medicine was a uniform criterion across the eight countries, whereas quality of evidence (under the remit of therapeutic impact assessment) and equity were infrequently cited criteria. Only the German HTA agency mandated that surrogate endpoints be validated in therapeutic impact assessment. All countries except Germany included formal cost-effectiveness analyses within HTA reports. England and Japan were the only countries that specified a cost-effectiveness threshold. Of the 34 medicine-indication pairs corresponding to US top-selling cancer medicines, Germany reimbursed the maximum (34 [100%]), followed by Italy (32 [94%] recommended for reimbursement), Japan (28 [82%] reimbursed), Australia, Canada, England, and France (27 [79%] recommended for reimbursement), and New Zealand (12 [35%] recommended for reimbursement). Of the 18 cancer medicine-indication pairs with marginal clinical benefit, Germany reimbursed 15 (83%) and Japan reimbursed 12 (67%). France recommended nine (50%) for reimbursement, followed by Italy (seven [39%]), Canada (five [28%]), and Australia and England (three [17%] each). New Zealand did not recommend any medicine-indications with marginal clinical benefit for reimbursement. Considering the overall cumulative proportion across the eight countries, 58 (21%) of 272 indications for the US top-selling medicines and 90 (63%) of 144 marginally beneficial medicine-indications were not recommended for reimbursement or reimbursed. INTERPRETATION: Our findings indicate discordance in public reimbursement decisions across economically similar countries, despite overlapping HTA decision criteria. This suggests a need for improved transparency around the nuances of the criteria to ensure improved access to high-value cancer medicines, and deprioritisation of low-value cancer medicines. Health systems have opportunities to improve their HTA decision-making processes by learning from the systems in other countries. FUNDING: None.

Transferable Exclusivity Vouchers and Incentives for Antimicrobial Development in the European Union.

The European Commission's proposal to address antimicrobial resistance using transferable exclusivity vouchers (TEVs) is fundamentally flawed. European policymakers and regulators should consider alternatives, such as better funding for basic and clinical research, use of advance market commitments funded by a pay-or-play tax, or enacting an EU Fund for Antibiotic Development.

Health-related quality of life measures in incarcerated populations: protocol for a scoping review.

INTRODUCTION: Incarcerated populations represent a vulnerable and marginalised segment of society, with increased health needs and a higher burden of communicable and non-communicable diseases. Traditional population health outcomes do not capture physical, mental, emotional and social well-being. Health-related quality of life (HRQoL) outcomes attempt to measure these important parameters. To date, there has not been a scoping review to summarise the HRQoL literature in the incarcerated population. Thus, we aim to perform such a review to inform health policy decisions in incarcerated populations and support health economic evaluations of interventions in incarcerated populations. METHODS AND ANALYSIS: We will conduct a scoping review of the literature on the HRQoL in the incarcerated population informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the corresponding PRISMA Extension for Scoping Reviews. The submissions records of six electronic databases with peer-reviewed literature and three health technology assessment agencies will be searched. The search strategy was informed by recommendations for HRQoL reviews. We will include studies that report HRQoL, health state utility values or reference to quality adjusted life years or quality-adjusted life expectancies of incarcerated populations. No assessments of items' quality will be made, as the purpose of this scoping review is to synthesise and describe the coverage of the evidence. We will also identify knowledge gaps on the HRQoL in the incarcerated population. ETHICS AND DISSEMINATION: Research ethics approval is not required as primary data will not be collected. The findings of this scoping review will be used to inform health economic analyses for the incarcerated population and will be disseminated through peer-reviewed publications and conference presentations.

Defining a Core Data Set for the Economic Evaluation of Precision Oncology.

OBJECTIVES: Precision oncology is generating vast amounts of multiomic data to improve human health and accelerate research. Existing clinical study designs and attendant data are unable to provide comparative evidence for economic evaluations. This lack of evidence can cause inconsistent and inappropriate reimbursement. Our study defines a core data set to facilitate economic evaluations of precision oncology. METHODS: We conducted a literature review of economic evaluations of next-generation sequencing technologies, a common application of precision oncology, published between 2005 and 2018 and indexed in PubMed (MEDLINE). Based on this review, we developed a preliminary core data set for informal expert feedback. We then used a modified-Delphi approach with individuals involved in implementation and evaluation of precision medicine, including 2 survey rounds followed by a final voting conference to refine the data set. RESULTS: Two authors determined that variation in published data elements was reached after abstraction of 20 economic evaluations. Expert consultation refined the data set to 83 unique data elements, and a multidisciplinary sample of 46 experts participated in the modified-Delphi process. A total of 68 elements (81%) were selected as required, spanning demographics and clinical characteristics, genomic data, cancer treatment, health and quality of life outcomes, and resource use. CONCLUSIONS: Cost-effectiveness analyses will fail to reflect the real-world impacts of precision oncology without data to accurately characterize patient care trajectories and outcomes. Data collection in accordance with the proposed core data set will promote standardization and enable the generation of decision-grade evidence to inform reimbursement.

Qualitative Research Informing a Preference Study on Selecting Cannabis for Cancer Survivor Symptom Management: Design of a Discrete Choice Experiment.

INTRODUCTION: The legalization of recreational cannabis use can enable cancer survivors to manage aspects of their care with cannabinoids without medical authorization or stigmatization. However, the absence of medical guidance-from the scientific literature or the healthcare system-makes it difficult for survivors to reach informed decisions about their care. OBJECTIVE: This article outlines the qualitative research undertaken to design a discrete choice experiment (DCE) aimed at understanding Canadian cancer survivors' preferences for managing their cancer symptoms with cannabis in this complex socio-medical context. METHODS: In this study, we drew on previously published qualitative research (a literature review and interviews with cancer survivors) and the theory of planned behavior, holding weekly team meetings to review the qualitative data and identify initial attributes associated with medicinal cannabis consumption to inform the DCE design. The initial attributes were further assessed to determine whether they were sensitive to the Canadian context, modifiable to produce levels and trade-offs, and amenable to policy intervention, in order to form the DCE choice sets. The choice sets were tested via think-aloud exercises with members of the general population and included debriefing interviews. Think-aloud participants were recruited from patient groups and previous studies. RESULTS: Based on our review of the interview study, we identified the following attributes associated with selecting medicinal cannabis: effectiveness; chance of side effects; support from family, friends, and/or physicians; cost; and availability. Ability to perform everyday activities was added and monthly out-of-pocket cost was refined to render the DCE realistic to cancer survivors in the Canadian context. Revisions to the DCE instructions, terminology, and cost levels were made based on results from the think-aloud exercises (n = 10). CONCLUSIONS: This qualitative study outlines the preference evidence collected regarding Canadian cancer survivors' decisions to manage their symptoms with cannabis to inform a DCE quantitative survey. It contributes to transparent reporting of qualitative work in DCE development and to understanding cancer survivors' preferences regarding medicinal cannabis consumption under legalization.

PET-Based Staging Is Cost-Effective in Early-Stage Follicular Lymphoma.

The objective was to assess the cost-effectiveness of staging PET/CT in early-stage follicular lymphoma (FL) from the Canadian health-care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding staging PET/CT versus using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a noncurative approach, or no change in RT treatment as planned. The subsequent disease course was described using a state-transition cohort model over a 30-y time horizon. Diagnostic characteristics, probabilities, utilities, and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars), and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5%. Results: In the reference case scenario, staging PET/CT was the dominant strategy, resulting in an average lifetime cost saving of $3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs) and was cost-effective in 89% of simulations (i.e., either saved costs or had an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis showed that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT before curative-intent RT.

Quality of End-of-Life Cancer Care in Canada: A 12-Year Retrospective Analysis of Three Provinces' Administrative Health Care Data Evaluating Changes over Time.

This retrospective cohort study of cancer decedents during 2004-2015 examined end-of-life cancer care quality indicators (QIs) in the provinces of British Columbia (BC), Ontario, and Nova Scotia (NS). These included: emergency department use, in-patient hospitalization, intensive care unit admissions, physician house calls, home care visits, and death experienced in hospital. Ontario saw the greatest 12-year decrease in in-hospital deaths from 52.8% to 41.1%. Hospitalization rates within 30 days of death decreased in Ontario, increased in NS, and remained the same in BC. Ontario's usage of aggressive end-of-life measures changed very little, while BC increased their utilization rates. Supportive care use increased in both NS and Ontario. Those who were male or living in a lower income/smaller community (in Ontario) were associated with a decreased likelihood of receiving supportive care. Despite the shift in focus to providing hospice and home care services, approximately 50% of oncology patients are still dying in hospital and 11.7% of patients overall are subject to aggressive care measures that may be out of line with their desire for comfort care. Supportive care use is increasing, but providers must ensure that Canadians are connected to palliative services, as its utilization improves a wide variety of outcomes.

Cost-Effectiveness Analysis of Stereotactic Ablative Body Radiotherapy for the Treatment of Oligometastatic Tumors versus Standard of Care.

BACKGROUND: Recent clinical trial results reported that stereotactic radiotherapy (SABR) may improve survival for patients with oligometastatic (OM) cancer. Given that these results come from a phase II trial, there remains considerable uncertainty about this finding, and about the cost-effectiveness of SABR for patients with OM cancer. In this analysis, we estimate the cost-effectiveness of SABR for oligometastatic cancer patients. METHODS: A probabilistic time-dependent Markov model was constructed to simulate treatment of oligometastatic cancer patients over five- and ten-year time horizons. The primary data source was the phase II, Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases (SABR-COMET )trial and supplemented with data from the literature. We estimated the effect of SABR and the standard of care (SoC) using quality-adjusted life-years (QALYs). Costs were measured from a provincial payer perspective (2018 Canadian dollars). RESULTS: In the reference case analysis (five-year time horizon), SABR was associated with additional incremental costs of CAD 38,487 and an incremental QALY gain of 0.84. This resulted in an incremental cost-effectiveness ratio (ICER) of CAD 45,726 per QALY gained. Over a ten-year time horizon, the increased uncertainty in the long-term effectiveness of SABR resulted in an ICER of CAD 291,544 per QALY gained. Estimates from the probabilistic analysis indicated that at a willingness-to-pay (WTP) threshold of CAD 50,000 and CAD 100,000 per QALY gained, there is 54% and 78% probability (respectively) that SABR would be cost-effective using the five-year time horizon. CONCLUSIONS: The adoption of SABR therapy requires a considerable upfront capital investment. Our results suggest that the cost-effectiveness of SABR is contingent on the uncertainty in the evidence base. Further clinical trials to confirm the effectiveness of SABR and research into the real-world costs associated with this treatment could reduce the uncertainty around implementation of the technology.

Experiences and perspectives of individuals accessing CAR-T cell therapy: A qualitative analysis of online Reddit discussions.

INTRODUCTION: Several chimeric antigen receptor (CAR-T) T-cell therapies have been approved for use for haematological malignancies. Despite known safety, access, and cost issues, little is known about how patients and caregivers understand novel treatments such as CAR-T and their associated uncertainties. METHODS: We gathered data from Reddit, an online public social media site. We performed a keyword search in three relevant subreddit threads: r/cancer, r/lymphoma, r/leukemia. We systematically extracted threads and associated comments and reviewed against our inclusion criteria. RESULTS: We identified a total of 186 posts and 87 were included in the qualitative analysis from March 1, 2013, to April 15, 2021. Qualitative content analysis was used to identify themes. Of those excluded, 88 contained discussions of other immunotherapies and 11 were scientific profiles. We identified four themes: 1) navigating uncertainty with community, 2) finding a cure, 3) managing treatment-related uncertainties, and 4) overcoming uncertainties related to access. We found patients experience numerous barriers when seeking access to novel therapeutics, such as CAR-T therapies. CONCLUSIONS: The perceptions and struggles of patients and their families are relevant for developing technology assessments that are sensitive to patient experiences, as well as to inform policies for equitable resource allocation. POLICY SUMMARY: Our study underscores the importance of balanced decision making between patients and physicians to ensure patients understand the risk and benefits of cancer treatments. Study investigators might evaluate trial participants based on patient demographics to ensure equitable access to studies for individuals in settings where internet access is less common.

Health-related quality of life data collected in chimeric antigen receptor T-cell (CAR-T) therapy clinical trials.

INTRODUCTION: Chimeric antigen receptor T-cell (CAR-T) therapy represents a novel approach to cancer treatment, particularly advanced cancer. Much of the current evidence for the effectiveness of these therapies is associated with considerable uncertainty. This uncertainty poses a challenge for decision-makers and health systems responsible for granting patients access to these therapies. While the stage of development of the technology is a component of this uncertainty, it can be reduced with relevant data collection alongside clinical trials that is meaningful to patients and decision-makers. The objective of this research was to investigate the frequency with which HRQoL data is collected in currently registered clinical trials investigating CAR-T cancer treatment. METHODS: We searched for current CAR-T clinical trials at a registry compiled at United States National Institutes of Health National Library of Medicine (NLM) database. Trials were required to be active, recruiting, or completed. Trials were required to be phase I-IV, listed as 'interventional', and specific to cancer treatment. RESULTS: There were 424 clinical trials that were included in our analysis. The majority of these trials (76 %) were investigating CAR-T therapy in haematological malignancies. Of the included studies, only 29 (6.8 %) included HRQoL as a primary or secondary outcome measure. Only 25 (5.9 %) trials reported collecting data on overall survival. CONCLUSIONS: This investigation into clinical trials for CAR-T therapies has shown a failure to collect valuable HRQoL data. Sponsors of clinical trials need to appreciate that clinical trials for novel therapies need to collect relevant data that is paramount to informing decision-making and providing access to patients. POLICY STATEMENT: The effectiveness of innovative cancer therapies, such as CAR-T, remains associated with considerable uncertainty. This uncertainty can be reduced for decision-makers via the collection of critical HRQoL data. Sponsors of clinical trials should be incentivized to collect these data, particularly where the intention is to use that trial for a reimbursement submission and decision..

Challenges with sex-specific subgroup analyses in oncology clinical trials for drug approvals between 2015-2020.

INTRODUCTION: Women continue to be underrepresented in oncology clinical trials, leading to poor, underpowered subgroup analyses that cannot be generalized to cancer patients in practice. In 2014, the US Food and Drug Administration (FDA) released an Action Plan, which included actions to improve the quality and reporting of demographic subgroup data. We sought to evaluate the five-year progress since the release of this report by assessing the credibility of sex-specific subgroup analyses in oncology clinical trials. METHODS: We reviewed the FDA Hematology/Oncology Approvals website for New Molecular Entities (NMEs) that were approved for adults from 2015 to 2020. Publications and their supplementary indexes were reviewed by two authors (K.J. & A.R.) against ten criteria that gauge the credibility of subgroup analyses by assessing factors related to study design, analysis, and context. One point was awarded for each criteria met, for a maximum score of 10. RESULTS: We identified a total of 73 NMEs approved for cancer treatment between 2015-2020, of which 61 met our eligibility criteria. Of these, 32 studies (52 %) reported a subgroup analysis by sex and were included in our analysis. Phase 2 (41 %) and Phase 3 (53 %) studies represented most studies. No study met ≥3 credibility criteria. CONCLUSION: Only half the studies included in our analysis reported outcomes by sex, which suggests the activities stipulated in the 2014 US FDA Action Plan might be ineffective. This is concerning as uncredible sex-specific subgroup analyses can lead to wrongful clinical decision-making and poor patient outcomes. POLICY SUMMARY: Our findings suggest sex-specific subgroup analyses in oncology are not credible and users of these data should interpret results with caution. Regulatory bodies, such as the US FDA, ought to mandate subgroup analyses by demographic groups in drug applications. Peer-reviewed journals could ensure investigators disclose study results by sex as a condition for publication.

Understanding cancer survivors' reasons to medicate with cannabis: A qualitative study based on the theory of planned behavior.

BACKGROUND: Prior to nonmedical cannabis legalization in Canada, individuals were only able to access cannabis legally through licensed producers with medical authorization. Now with an additional legal access system designed for nonmedical purposes, it is unclear what factors influence cancer survivors' decisions to medicate or not medicate cannabis as a complementary therapy to alleviate their cancer symptoms. METHODS: We recruited cancer survivors via social media. Interested individuals were purposively sampled to ensure maximization in terms of age, sex, and province of residence. Constructs of the Theory of Planned Behavior were explored during the telephone interviews as participants described what influenced their decisions to medicate or not medicate cannabis to manage their symptoms. RESULTS: Interviews were conducted with 33 cancer survivors. All individuals believed that cannabis would manage their cancer symptoms. Those that chose to medicate with cannabis provided a variety of reasons, including that cannabis was a more natural alternative; that it reduced their overall number of prescription drugs; and that safer products had become available with the legalization of nonmedical cannabis. Some individuals also indicated that support from physicians and validation from family and friends were important in their decision to medicate with cannabis. Individuals who opted not to medicate with cannabis raised concerns about the lack of scientific evidence and/or possible dependency issues. Some also felt their physician's disapproval was a barrier to considering cannabis use. CONCLUSIONS: The findings revealed that recreational legalization made using cannabis appear safer and easier to access for some cancer survivors. However, physicians' censure of cannabis use for symptom management was a barrier for survivors considering its use.