Implications of Oncology Trial Design and Uncertainties in Efficacy-Safety Data on Health Technology Assessments

Abstract

Background: Advances in cancer medicines have resulted in tangible health impacts, but the magnitude of benefits of approved cancer medicines could vary greatly. Health Technology Assessment (HTA) is a multidisciplinary process used to inform resource allocation through a systematic value assessment of health technology. This paper reviews the challenges in conducting HTA for cancer medicines arising from oncology trial designs and uncertainties of safety-efficacy data. Methods: Multiple databases (PubMed, Scopus and Google Scholar) and grey literature (public health agencies and governmental reports) were searched to inform this policy narrative review. Results: A lack of robust efficacy-safety data from clinical trials and other relevant sources of evidence has made HTA for cancer medicines challenging. The approval of cancer medicines through expedited pathways has increased in recent years, in which surrogate endpoints or biomarkers for patient selection have been widely used. Using these surrogate endpoints has created uncertainties in translating surrogate measures into patient-centric clinically (survival and quality of life) and economically (cost-effectiveness and budget impact) meaningful outcomes, with potential effects on diverting scarce health resources to low-value or detrimental interventions. Potential solutions include policy harmonization between regulatory and HTA authorities, commitment to generating robust post-marketing efficacy-safety data, managing uncertainties through risk-sharing agreements, and using value frameworks. Conclusion: A lack of robust efficacy-safety data is a central problem for conducting HTA of cancer medicines, potentially resulting in misinformed resource allocation.

What’s the reality for CDK4/6 inhibitors: Clinical trials or real‐world evidence?

“…Ideally RWE should primarily be used to inform policymaking, through analysis of patterns of health service utilization and identification of structural barriers to access to care, and to help shape strategies for patient-centric coverage and reimbursement decisions, including in the context of health technology assessments. 19,20 In conclusion, the SEER-analysis by Goyal et al 2 presents confirmatory RWE for the benefit of CDK4/6 inhibitors observed in clinical trials for endocrine sensitive, de novo, metastatic BC in an older population. However, this evidence is not a substitute for the results from phase 3, randomized clinical trials.…”

“…Randomization intrinsically minimizes bias in patient selection, ensuring fair comparisons across balanced groups. Ideally RWE should primarily be used to inform policymaking, through analysis of patterns of health service utilization and identification of structural barriers to access to care, and to help shape strategies for patient‐centric coverage and reimbursement decisions, including in the context of health technology assessments 19,20 …”

Surrogate Measures of Drug Efficacy—A Finger Pointing at the Moon

“…Such mandatory reassessment, particularly for drugs originally approved on the basis of potentially unreliable surrogate measures, could also be an opportunity to require follow-up clinical studies conducted while a drug is in routine use. This kind of ongoing evaluation is far more useful for clinicians, patients, and policy makers than a simplistic approval decision made at a single, early point in time on the basis of potentially inadequate outcome measures but not informed by further evidence . Experience in the US indicates that manufacturers are often slow or even inert in implementing such postmarketing requirements required by the Food and Drug Administration, but the concept of reexamination does open the door to such a more systematic assessment after a drug has been approved quickly on the basis of less dependable measures.…”

“…This kind of ongoing evaluation is far more useful for clinicians, patients, and policy makers than a simplistic approval decision made at a single, early point in time on the basis of potentially inadequate outcome measures but not informed by further evidence. 7 Experience in the US indicates that manufacturers are often slow or even inert in implementing such postmarketing requirements required by the Food and Drug Administration, 8,9…”

The value of patient reported outcomes in palliative radiotherapy: A discussion in light of current findings

“…This is important because traditional endpoints in interventional cancer trials, such as progression-free survival (PFS) or overall survival, do not correlate well with QoL (8). Surrogate endpoints have created uncertainties in translating surrogate measures into patient-centric clinically and economically meaningful outcomes (9). Nevertheless, in the last decade, such surrogate markers like PFS and tumour response have been increasingly used in clinical trials to reduce trial cost by…”