Evaluating the Value for Money of Precision Medicine from Early Cycle to Market Access: A Comprehensive Review of Approaches and Challenges.

OBJECTIVES: This study aimed to perform a comprehensive review of modeling approaches and methodological and policy challenges in the economic evaluation (EE) of precision medicine (PM) across clinical stages. METHODS: First, a systematic review was performed to assess the approaches of EEs in the past 10 years. Next, a targeted review of methodological articles was conducted for methodological and policy challenges in performing EEs of PM. All findings were synthesized into a structured framework that focused on patient population, Intervention, Comparator, Outcome, Time, Equity and ethics, Adaptability and Modeling aspects, named the "PICOTEAM" framework. Finally, a stakeholder consultation was conducted to understand the major determinants of decision making in PM investment. RESULTS: In 39 methodological articles, we identified major challenges to the EE of PM. These challenges include that PM applications involve complex and evolving clinical decision space, that clinical evidence is sparse because of small subgroups and complex pathways in PM settings, a one-time PM application may have lifetime or intergenerational impacts but long-term evidence is often unavailable, and that equity and ethics concerns are exceptional. In 275 EEs of PM, current approaches did not sufficiently capture the value of PM compared with targeted therapies, nor did they differentiate Early EEs from Conventional EEs. Finally, policy makers perceived the budget impact, cost savings, and cost-effectiveness of PM as the most important determinants in decision making. CONCLUSIONS: There is an urgent need to modify existing guidelines or develop a new reference case that fits into the new healthcare paradigm of PM to guide decision making in research and development and market access.

Mapping the value for money of precision medicine: a systematic literature review and meta-analysis.

Objective: This study aimed to quantify heterogeneity in the value for money of precision medicine (PM) by application types across contexts and conditions and to quantify sources of heterogeneity to areas of particular promises or concerns as the field of PM moves forward. Methods: A systemic search was performed in Embase, Medline, EconLit, and CRD databases for studies published between 2011 and 2021 on cost-effectiveness analysis (CEA) of PM interventions. Based on a willingness-to-pay threshold of one-time GDP per capita of each study country, the net monetary benefit (NMB) of PM was pooled using random-effects meta-analyses. Sources of heterogeneity and study biases were examined using random-effects meta-regressions, jackknife sensitivity analysis, and the biases in economic studies checklist. Results: Among the 275 unique CEAs of PM, publicly sponsored studies found neither genetic testing nor gene therapy cost-effective in general, which was contradictory to studies funded by commercial entities and early stage evaluations. Evidence of PM being cost-effective was concentrated in a genetic test for screening, diagnosis, or as companion diagnostics (pooled NMBs, $48,152, $8,869, $5,693, p < 0.001), in the form of multigene panel testing (pooled NMBs = $31,026, p < 0.001), which only applied to a few disease areas such as cancer and high-income countries. Incremental effectiveness was an essential value driver for varied genetic tests but not gene therapy. Conclusion: Precision medicine's value for money across application types and contexts was difficult to conclude from published studies, which might be subject to systematic bias. The conducting and reporting of CEA of PM should be locally based and standardized for meaningful comparisons.

Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry.

BACKGROUND: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone. OBJECTIVE: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS. METHODS: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models. RESULTS: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48]). CONCLUSIONS: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization.

Public acceptability of COVID-19 control measures in Singapore, Hong Kong, and Malaysia: A cross-sectional survey.

BACKGROUND: Several countries have implemented control measures to limit SARS-CoV-2 spread, including digital contact tracing, digital monitoring of quarantined individuals, and testing of travelers. These raise ethical issues around privacy, personal freedoms, and equity. However, little is known regarding public acceptability of these measures. METHODS: In December 2020, we conducted a survey among 3635 respondents in Singapore, Hong Kong, and Malaysia to understand public perceptions on the acceptability of COVID-19 control measures. FINDINGS: Hong Kong respondents were much less supportive of digital contact tracing and monitoring devices than those in Malaysia and Singapore. Around three-quarters of Hong Kong respondents perceived digital contact tracing as an unreasonable restriction of individual freedom; <20% trusted that there were adequate local provisions preventing these data being used for other purposes. This was the opposite in Singapore, where nearly 3/4 of respondents agreed that there were adequate data protection rules locally. In contrast, only a minority of Hong Kong respondents viewed mandatory testing and vaccination for travelers as unreasonable infringements of privacy or freedom. Less than 2/3 of respondents in all territories were willing to be vaccinated against COVID-19, with a quarter of respondents undecided. However, support for differential travel restrictions for vaccinated and unvaccinated individuals was high in all settings. INTERPRETATION: Our findings highlight the importance of sociopolitical context in public perception of public health measures and emphasize the need to continually monitor public attitudes toward such measures to inform implementation and communication strategies.