Overall survival benefits of cancer drugs initially approved by the US Food and Drug Administration on the basis of immature survival data: a retrospective analysis.

BACKGROUND: New cancer drugs can be approved by the US Food and Drug Administration (FDA) on the basis of surrogate endpoints while data on overall survival are still incomplete or immature, with too few deaths for meaningful analysis. We aimed to evaluate whether clinical trials with immature survival data generated evidence of overall survival benefit during the period after marketing authorisation, and where that evidence was reported. METHODS: In this retrospective analysis, we searched Drugs@FDA to identify cancer drug indications approved between Jan 1, 2001, and Dec 31, 2018, on the basis of immature survival data. We systematically collected publicly available data on postapproval overall survival results in labelling (Drugs@FDA), journal publications (MEDLINE via PubMed), and clinical trial registries (ClinicalTrials.gov). The primary outcome was availability of statistically significant overall survival benefits during the period after marketing authorisation (until March 31, 2023). Additionally, we evaluated the availability and timing of overall survival findings in labelling, journal publications, and ClinicalTrials.gov records. FINDINGS: During the study period, the FDA granted marketing authorisation to 223 cancer drug indications, 95 of which had overall survival as an endpoint. 39 (41%) of these 95 indications had immature survival data. After a minimum of 4·3 years of follow-up during the period after marketing authorisation (and median 8·2 years [IQR 5·3-12·0] since FDA approval), additional survival data from the pivotal trials became available in either revised labelling or publications, or both, for 38 (97%) of 39 indications. Additional data on overall survival showed a statistically significant benefit in 12 (32%) of 38 indications, whereas mature data yielded statistically non-significant overall survival findings for 24 (63%) indications. Statistically significant evidence of overall survival benefit was reported in either labelling or publications a median of 1·5 years (IQR 0·8-2·3) after initial approval. The median time to availability of statistically non-significant overall survival results was 3·3 years (2·2-4·5). The availability of overall survival results on ClinicalTrials.gov varied considerably. INTERPRETATION: Fewer than a third of indications approved with immature survival data showed a statistically significant overall survival benefit after approval. Notable inconsistencies in timing and availability of information after approval across different sources emphasise the need for better reporting standards. FUNDING: None.

Financial Toxicity of Withdrawn Poly (Adenosine Diphosphate Ribose) Polymerase Inhibitor Indications for Ovarian Cancer.

OBJECTIVES: We sought to quantify exposure to and financial impacts of poly (adenosine diphosphate ribose) polymerase inhibitor (PARPi) treatments for eventually withdrawn ovarian cancer indications. METHODS: We identified in Optum's deidentified Clinformatics® Data Mart database 1695 patients with ovarian cancer diagnoses who received olaparib, rucaparib, or niraparib between January 2015 and September 2021. We describe PARPi use and out-of-pocket, total healthcare, and PARPi spending among patients with ovarian cancer with 3 or more previous lines of therapy. RESULTS: Of the 1695 patients who received PARPi, 254 were estimated to have been heavily pretreated and exposed to eventually withdrawn indications. Cumulative total medical and pharmacy costs for these patients were $53 392 184; PARPi costs accounted for 34%. Median PARPi cost per patient was $43 347. Cumulative out-of-pocket costs totaled $533 281. CONCLUSIONS: Potential patient harm, including financial toxicity, might have been mitigated through more stringent drug approval requirements.

Forecasting essential childhood cancer drug need: An innovative model-based approach.

BACKGROUND: Childhood cancer outcomes in low-income and middle-income countries have not kept pace with advances in care and survival in high-income countries. A contributing factor to this survival gap is unreliable access to essential drugs. METHODS: The authors created a tool (FORx ECAST) capable of predicting drug quantity and cost for 18 pediatric cancers. FORx ECAST enables users to estimate the quantity and cost of each drug based on local incidence, stage breakdown, treatment regimen, and price. Two country-specific examples are used to illustrate the capabilities of FORx ECAST to predict drug quantities. RESULTS: On the basis of domestic public-sector price data, the projected annual cost of drugs to treat childhood cancer cases is 0.8 million US dollars in Kenya and 3.0 million US dollars in China, with average median price ratios of 0.9 and 0.1, respectively, compared with costs sourced from the Management Sciences for Health (MSH) International Medical Products Price Guide. According to the cumulative chemotherapy cost, the most expensive disease to treat is acute lymphoblastic lymphoma in Kenya, but a higher relative unit cost of methotrexate makes osteosarcoma the most expensive diagnosis to treat in China. CONCLUSIONS: FORx ECAST enables needs-based estimates of childhood cancer drug volumes to inform health system planning in a wide range of contexts. It is broadly adaptable, allowing decision makers to generate results specific to their needs. The resultant estimates of drug need can help equip policymakers and health governance institutions with evidence-informed data to advance innovative procurement strategies that drive global improvements in childhood cancer drug access.

Integrating public preferences into national reimbursement decisions: a descriptive comparison of approaches in Belgium and New Zealand.

BACKGROUND: Public health care payer organizations face increasing pressures to make transparent and sustainable coverage decisions about ever more expensive prescription drugs, suggesting a need for public engagement in coverage decisions. However, little is known about countries' approaches to integrating public preferences in existing funding decisions. The aim of this study was to describe how Belgium and New Zealand used deliberative processes to engage the public and to identify lessons learned from these countries' approaches. METHODS: To describe two countries' deliberative processes, we first reviewed key country policy documents and then conducted semi-structured interviews with five leaders of the processes from Belgium and New Zealand. We assessed each country's rationales for and approaches to engaging the public in pharmaceutical coverage decisions and identified lessons learned. We used qualitative content analysis of the interviews to describe key themes and subthemes. RESULTS: In both countries, the national public payer organization initiated and led the process of integrating public preferences into national coverage decision making. Reimbursement criteria considered outdated and changing societal expectations prompted the change. Both countries chose a deliberative process of public engagement with a multi-year commitment of many stakeholders to develop new reimbursement processes. Both countries' new reimbursement processes put a stronger emphasis on quality of life, the separation of individual versus societal perspectives, and the importance of final reimbursement decisions being taken in context rather than based largely on cost-effectiveness thresholds. CONCLUSIONS: To face the growing financial pressure of sustainable funding of medicines, Belgium's and New Zealand's public payers have developed processes to engage the public in defining the reimbursement system's priorities. Although these countries differ in context and geographic location, they came up with overlapping lessons learnt which include the need for 1) political commitment to initiate change, 2) broad involvement of all stakeholders, and 3) commitment of all to engage in a long-term process. To evaluate these changes, further research is required to understand how coverage decisions in systems with and without public engagement differ.

Total and out-of-pocket expenditures among women with metastatic breast cancer in low-deductible versus high-deductible health plans.

PURPOSE: High-deductible health plan (HDHP) enrollment is expanding rapidly and might substantially increase out-of-pocket (OOP) payment burden. We examined trends in total and OOP health service expenditures overall and by insurance coverage type among women with metastatic breast cancer. METHODS: We used a longitudinal time series design to examine measures among 5364 women with metastatic breast cancer insured by a large US health insurer from 2004 to 2011. We measured outcomes during the 12 months after a first identified metastatic breast cancer diagnosis and required women to have at least 6 months of prior enrollment. We plotted enrollment measures and adjusted total and OOP spending. We fit trend lines using linear autoregressive models. RESULTS: Between 2004 and 2011, the percentage of women with metastatic breast cancer enrolled in employer-mandated HDHPs increased from 8 to 23% while the percentage enrolled in employer-mandated low-deductible plans (LDHPs) decreased from 69 to 37%. Over the same time period, estimated annual inflation-adjusted total health service spending among women with metastatic breast cancer whose employers only offered HDHPs or LDHPS increased from $96,899 to $104,688 (increase of $1197 per year; 95% confidence interval [CI]: $47,$2,348). Corresponding OOP spending values among these women with employer-mandated deductible levels were $4,496 and $5,151 ($91 per year trend; 95% CI -$13,$195). From 2004-2011, women in HDHPs and LDHPs had unchanged annual OOP spending, estimated at of $6642 (95% CI $6,268,$7016) and $4,247 (95% CI $3956,$4538), respectively. Thus, women in HDHPs experienced 55% (44%, 66%) more OOP spending than women in LDHP. CONCLUSIONS: OOP spending among women with metastatic breast cancer and employer-mandated deductible levels was 55% higher among HDHP than LDHP members, and employer-mandated HDHP enrollment increased substantially from 2004 to 2011. Stakeholders and policymakers should design health plans that protect financially vulnerable cancer patients from high OOP costs.

Impact of high-deductible insurance on adjuvant hormonal therapy use in breast cancer.

OBJECTIVE: High-deductible health plans (HDHPs) have become the predominant commercial health insurance arrangement in the US. HDHPs require substantial out-of-pocket (OOP) costs for most services but often exempt medications from high cost sharing. We examined effects of HDHPs on OOP costs and utilization of adjuvant hormonal therapy (AHT), which are fundamental care for patients with breast cancer. METHODS: This controlled quasi-experimental study used claims data (2003-2012) from a large national health insurer. We included 986 women with incident early-stage breast cancer, age 25-64 years, insured by employers that mandated a transition from low-deductible (≤ $500/year) to high-deductible (≥ $1000/year) coverage, and 3479 propensity score-matched controls whose employers offered only low-deductible plans. We examined AHT utilization and OOP costs per person-year before and after the HDHP switch. RESULTS: At baseline, the OOP costs for AHT were $40.41 and $36.55 per person-year among the HDHP and control groups. After the HDHP switch, the OOP costs for AHT were $91.76 and $72.98 per person-year among the HDHP and control groups, respectively. AHT OOP costs increased among HDHP members relative to controls but the change was not significant (relative change 13.72% [95% CI - 9.25, 36.70%]). AHT use among HDHP members did not change compared to controls (relative change of 2.73% [95% CI - 14.01, 19.48%]); the change in aromatase inhibitor use was - 11.94% (95% CI - 32.76, 8.88%) and the change in tamoxifen use was 20.65% (95% CI - 8.01, 49.32%). CONCLUSION: We did not detect significant changes in AHT use after the HDHP switch. Findings might be related to modest increases in overall AHT OOP costs, the availability of low-cost generic tamoxifen, and patient awareness that AHT can prolong life and health. Minimizing OOP cost increases for essential medications might represent a feasible approach for maintaining medication adherence among HDHP members with incident breast cancer.

State Medicaid Reimbursement for Medications for Chronic Hepatitis C Infection from 2012 through 2015.

BACKGROUND: New direct-acting antivirals (DAAs) can cure chronic hepatitis C virus (HCV) infection. High DAA prices combined with a large number of patients needing treatment may pose substantial economic burden on health systems. OBJECTIVES: To examine Medicaid reimbursement for medications for HCV infection before and after the availability of new DAAs overall and by state and to also assess the impact of Medicaid expansion on reimbursement for DAAs. METHODS: We calculated Medicaid reimbursements for medications for HCV infection between 2012 and 2015 in all 50 states and the District of Columbia. Outcomes included inflation-adjusted Medicaid reimbursement for medications for HCV infection, market share of individual DAAs, percentages of Medicaid outpatient pharmacy reimbursement for DAAs, and Medicaid reimbursement per Medicaid enrollee with HCV infection. RESULTS: Medicaid reimbursement for medications for HCV infection increased from $723 million in 2012 to $2.35 billion in 2015. We found variations in Medicaid reimbursement for DAAs between states in 2014 (up to 7.4 times HCV infection prevalence) that widened in 2015 (0.1-11.4 times HCV infection prevalence). Expansion states had significantly higher increases in reimbursement for DAAs per enrollee with HCV infection compared with non- or late-expansion states ($2178.60; 95% confidence interval $1558.90-$2798.40), controlling for pre-expansion reimbursement. CONCLUSIONS: Medicaid reimbursement for DAAs differs across states after controlling for HCV infection prevalence. A third of states contributed more than 5% to 15% of pharmacy reimbursements to DAAs. Medications for HCV infection are only one class of highly priced specialty drugs. Innovative policy strategies are needed for health systems to manage coverage for an increasing number of expensive specialty medications indicated for an increasing number of patients.

Association Between Preapproval Confirmatory Trial Initiation and Conversion to Traditional Approval or Withdrawal in the FDA Accelerated Approval Pathway.

This study examines the Food and Drug Administration's accelerated approval pathway and whether preapproval initiation was associated with faster conversion to traditional approval or withdrawal for drugs with nononcology indications.

Drivers of expenditure on primary care prescription drugs in 10 high-income countries with universal health coverage.

BACKGROUND: Managing expenditures on pharmaceuticals is important for health systems to sustain universal access to necessary medicines. We sought to estimate the size and sources of differences in expenditures on primary care medications among high-income countries with universal health care systems. METHODS: We compared data on the 2015 volume and cost per day of primary care prescription drug therapies purchased in 10 high-income countries with various systems of universal health care coverage (7 from Europe, in addition to Australia, Canada and New Zealand). We measured total per capita expenditure on 6 categories of primary care prescription drugs: hypertension treatments, pain medications, lipid-lowering medicines, noninsulin diabetes treatments, gastrointestinal preparations and antidepressants. We quantified the contributions of 5 drivers of the observed differences in per capita expenditures. RESULTS: Across countries, the average annual per capita expenditure on the primary care medicines studied varied by more than 600%: from $23 in New Zealand to $171 in Switzerland. The volume of therapies purchased varied by 41%: from 198 days per capita in Norway to 279 days per capita in Germany. Most of the differences in average expenditures per capita were driven by a combination of differences in the average mix of drugs selected within therapeutic categories and differences in the prices paid for medicines prescribed. INTERPRETATION: Significant international differences in average expenditures on primary care medications are driven primarily by factors that contribute to the average daily cost of therapy, rather than differences in the volume of therapy used. Average expenditures were lower among single-payer financing systems that appeared to promote lower prices and the selection of lower-cost treatment options.

Racial disparities in all-cause mortality among younger commercially insured women with incident metastatic breast cancer.

Racial disparities in breast cancer mortality persist and are likely related to multiple factors. Over the past decade, progress has been made in treating metastatic breast cancer, particularly in younger women. Whether disparities exist in this population is unknown. Using administrative claims data between 2000 and 2011 (OptumInsight, Eden Prairie, MN) of members insured through a large national US health insurer, we identified women aged 25-64 years diagnosed with incident metastatic breast cancer diagnosed between November 1, 2000, and December 31, 2008. We examined time from diagnosis to death, with up to 3 years of follow-up. We stratified analyses by geocoded race and socio-economic status, age-at-diagnosis, morbidity score, US region of residence, urban/non-urban, and years of diagnosis. We constructed Kaplan-Meier survival plots and analyzed all-cause mortality using multivariate Cox proportional hazard models. Among 6694 women with incident metastatic breast cancer (78 % Caucasian, 4 % African American, and 18 % other), we found higher mortality rates among women residing in predominantly African American versus Caucasian neighborhoods (hazard ratio (HR) 1.84; 95 % confidence interval, CI 1.39-2.45), women with high versus lower morbidity (HR 1.30 [1.12-1.51]), and women whose incident metastatic diagnosis was during 2000-2004 versus 2005-2008 (HR 1.60 [1.39-1.83]). Caucasian (HR 0.61 [0.52-0.71]) but not African American women (HR not significant) experienced improved mortality in 2005-2008 versus 2000-2004. Despite insured status, African American women and women with multi-morbidity had poorer survival. Only Caucasian women had improved mortality over time. Modifiable risk factors for increased mortality need to be addressed in order to reduce disparities.

Impacts of a new insurance benefit with capitated provider payment on healthcare utilization, expenditure and quality of medication prescribing in China.

OBJECTIVES: To assess a new Chinese insurance benefit with capitated provider payment for common diseases in outpatients. METHODS: Longitudinal health insurance claims data, health administrative data and primary care facility data were used to assess trajectories in outpatient visits, inpatient admissions, expenditure per common disease outpatient (CD/OP) visit and prescribing indicators over time. We conducted segmented regression analyses of interrupted time series data to measure changes in level and trend overtime, and cross-sectional comparisons against external standards. RESULTS: The number of total outpatient visits at 46 primary care facilities (on the CD/OP benefit as of July 2012) increased by 46 895 visits/month (P = 0.004, 95% CI: 15 795-77 994); the average number of CD/OP visits reached 1.84/year/enrollee in 2012; monthly inpatient admissions dropped from 6.4 (2009) to 4.3 (2012) per 1000 enrollees; the median total expenditure per CD/OP visit dropped by CNY 15.40 (P = 0.16, 95% CI: -36.95~6.15); injectable use dropped by 7.38% (P = 0.03, 95% CI: -14.08%~-0.68%); antibiotic use was not improved. CONCLUSIONS: Zhuhai's new CD/OP benefit with capitated provider payment has expanded access to primary care, which may have led to a reduction in expensive specialist inpatient services for CD/OP benefit enrollees. Cost awareness was likely raised, and rapidly growing expenditures were contained. Although having been partially improved, inappropriate prescribing of antibiotics and injectables was still prevalent. More explicit incentives and specific quality of care targets must be incorporated into the capitated provider payment to promote scientifically sound and cost-effective care and treatment.

Thirty Years of Media Coverage on High Drug Prices in the United States--A Never-Ending Story or a Time for Change?

In recent years drug prices have increasingly become a topic of debate for patients, providers, payers and policy makers. To place the current drug price debate into historical context, we searched the New York Times and Wall Street Journal from 1985 - 2015 and found that concerns about drug prices have commonly featured in the press over the study period with recently stronger calls for change. Price levels, types of innovations, stakeholder responses, and strategies to address high prices discussed in the media suggest that concerted efforts are required to enable affordable and high-value innovations.

Effects of safety warnings and risk management plan for Thiazolidinediones in Taiwan.

PURPOSE: To evaluate changes in thiazolidinedione use and quality of prescription following safety warnings for thiazolidinediones and cardiac risk in 2007, Risk Management Plan (RMP) policy for rosiglitazone in 2010, and warning for pioglitazone and bladder cancer risk in 2010 in Taiwan. METHODS: We obtained 2003-2011 claims data from Taiwan's National Health Insurance Research Database. Using an interrupted time series design and segmented regression, we estimated changes in monthly prescribing rates for thiazolidinediones among all and prevalent diabetes patients with and without cardiovascular disease history (CV history). We also compared time to prescription of thiazolidinediones among new diabetes patients with CV history before and after each regulatory action using survival analysis. RESULTS: Among prevalent patients with and without CV history, the prescribing rates of rosiglitazone decreased 36.88% and 28.92% after safety warnings in 2007 respectively. Pioglitazone prescriptions increased 13% among patients with CV history, but no changes were detected among patients without CV history. After rosiglitazone's RMP policy in 2010, large reductions in prescriptions were observed in patients with CV history (-101.67%) and those without CV history (-88.04%). Among new diabetes patients with CV history, cardiac safety warnings in 2007 significantly delayed the prescription of rosiglitazone, but no significant change was found for pioglitazone. CONCLUSIONS: The Taiwan FDA regulatory actions for thiazolidinediones communicated possible risks of cardiac events and bladder cancer. Different safety regulatory actions had differential impacts on the use of rosiglitazone and pioglitazone and the quality use of these drugs among the high-risk patients.

Effect of the economic recession on pharmaceutical policy and medicine sales in eight European countries.

OBJECTIVE: To identify pharmaceutical policy changes during the economic recession in eight European countries and to determine whether policy measures resulted in lower sales of, and less expenditure on, pharmaceuticals. METHODS: Information on pharmaceutical policy changes between 2008 and 2011 in eight European countries was obtained from publications and pharmaceutical policy databases. Data on the volume and value of the quarterly sales of products between 2006 and 2011 in the 10 highest-selling therapeutic classes in each country were obtained from a pharmaceutical market research database. We compared these indicators in economically stable countries; Austria, Estonia and Finland, to those in economically less stable countries, Greece, Ireland, Portugal, Slovakia and Spain. FINDINGS: Economically stable countries implemented two to seven policy changes each, whereas less stable countries implemented 10 to 22 each. Of the 88 policy changes identified, 33 occurred in 2010 and 40 in 2011. They involved changing out-of-pocket payments for patients in 16 cases, price mark-up schemes in 13 and price cuts in 11. Sales volumes increased moderately in all countries except Greece and Portugal, which experienced slight declines after 2009. Sales values decreased in both groups of countries, but fell more in less stable countries. CONCLUSION: Less economically stable countries implemented more pharmaceutical policy changes during the recession than economically stable countries. Unexpectedly, pharmaceutical sales volumes increased in almost all countries, whereas sales values declined, especially in less stable countries.

Impact of pharmaceutical policy interventions on utilization of antipsychotic medicines in Finland and Portugal in times of economic recession: interrupted time series analyses.

OBJECTIVES: To analyze the impacts of pharmaceutical sector policies implemented to contain country spending during the economic recession--a reference price system in Finland and a mix of policies including changes in reimbursement rates, a generic promotion campaign and discounts granted to the public payer in Portugal - on utilization of, as a proxy for access to, antipsychotic medicines. METHODOLOGY: We obtained monthly IMS Health sales data in standard units of antipsychotic medicines in Portugal and Finland for the period January 2007 to December 2011. We used an interrupted time series design to estimate changes in overall use and generic market shares by comparing pre-policy and post-policy levels and trends. RESULTS: Both countries' policy approaches were associated with slight, likely unintended, decreases in overall use of antipsychotic medicines and with increases in generic market shares of major antipsychotic products. In Finland, quetiapine and risperidone generic market shares increased substantially (estimates one year post-policy compared to before, quetiapine: 6.80% [3.92%, 9.68%]; risperidone: 11.13% [6.79%, 15.48%]. The policy interventions in Portugal resulted in a substantially increased generic market share for amisulpride (estimate one year post-policy compared to before: 22.95% [21.01%, 24.90%]; generic risperidone already dominated the market prior to the policy interventions. CONCLUSIONS: Different policy approaches to contain pharmaceutical expenditures in times of the economic recession in Finland and Portugal had intended--increased use of generics--and likely unintended--slightly decreased overall sales, possibly consistent with decreased access to needed medicines--impacts. These findings highlight the importance of monitoring and evaluating the effects of pharmaceutical policy interventions on use of medicines and health outcomes.

Quality use of medicines within universal health coverage: challenges and opportunities.

BACKGROUND: Medicines are a major driver of quality, safety, equity, and cost of care in low and middle-income country health systems. Universal health coverage implementers must explicitly address appropriate use of medicines to realize the health benefits of medicines, avoid wasting scarce resources, and sustain the financial viability of universal health coverage schemes. DISCUSSION: Medicines are major contributors to the health and well-being of individuals and populations when used appropriately, and they waste resources and endanger health when used unnecessarily or incorrectly. Stakeholders need to balance inherently competing objectives in the pharmaceutical sector. Emerging and expanding UHC schemes provide potential levers to balance competing system objectives.To use these levers, sustainable universal coverage programs will require a) information systems that can track medicines utilization, expenditures, and quality of medicines use; b) routine monitoring of indicators of medicines availability, access, affordability, and use; c) policies and programs that facilitate appropriate medicines use by prescribers, dispensers, and patients; d) transparency in setting priorities for medicines coverage under resource constraints; and e) a system perspective to engage diverse actors.As they operationalize paths toward universal health coverage and include targeted medicines coverage policies and programs, systems can build on, and innovate, pharmaceutical policy frameworks and management tools from different countries' settings. SUMMARY: Ensuring that medicines which achieve important health outcomes are available, accessible to all, used appropriately, and sustainably affordable is essential for realizing universal health coverage. Stakeholder cooperation and use of information and financing system levers provide opportunities to work toward this goal.

Regulatory histories of recently withdrawn ovarian cancer treatment indications of 3 PARP inhibitors in the US and Europe: lessons for the accelerated approval pathway.

Background: Withdrawals of drug indications may reveal potential inadequacies in the regulatory approval processes of new drugs. Understanding potential weaknesses of the regulatory approval process is paramount given the increasing use of expedited pathways. In this paper, we focus on three poly-ADP-ribose polymerase inhibitors (olaparib, rucaparib and niraparib) for the treatment of women with heavily pretreated, recurrent ovarian cancer, which were eventually withdrawn. Methods: We use a comparative case study approach to evaluate the regulatory histories of these drug indications in the US and Europe. Results: Two drug indications benefited from the FDA's accelerated approval pathway, which explicitly lowers the bar for evidence of efficacy at the time of approval. Following accelerated approval, manufacturers are mandated to conduct post-marketing studies to confirm clinical benefit. The FDA granted accelerated approval to olaparib and rucaparib based on data on surrogate endpoints and converted the approval to regular approval after the submission of additional data on surrogate endpoints from one of two required confirmatory trials, that is, without data on clinical benefit. Niraparib directly received regular approval based only on data on a surrogate endpoint. By contrast, the EMA granted conditional marketing authorisation to rucaparib and was quicker to restrict usage than the FDA. Conclusion: The regulatory histories of these drug indications highlight the need to reform the accelerated approval pathway by ensuring that post-marketing requirements are followed, and that regular approval is only based on evidence of clinical benefit.

Cancer drug indication approvals in China and the United States: a comparison of approval times and clinical benefit, 2001-2020.

Background: Perceived delays in cancer drug approvals have been a major concern for policymakers in China. Policies have been implemented to accelerate the launch of new cancer drugs and indications. This study aimed to assess similarities and differences between China and the United States in the approvals, timing, and clinical benefit evidence of cancer drug indications between 2001 and 2020. Methods: This study retrospectively identified all cancer drugs and indications approved in both China and the United States from January 1st, 2001 to December 31, 2020, and described differences in approval times as well as in submission and review times. Information on the availability of overall survival benefit evidence by December 31, 2020, was collected. Univariate and multiple logistic regression analyses were used to assess whether evidence of benefit and other factors affected the propensity and timing of approvals of cancer drug indications in China. Findings: Between 2001 and 2020, 229 indications corresponding to 145 cancer drugs approved in the United States were identified. Of those, 80 indications (34.9%) were also approved in China by the end of 2020. Cancer drug indications were approved in China at a median of 1273.5 days after approval in the United States. The median submission and review time differences for cancer drug indications in China were 1198.0 days and 180.0 days respectively. Submission time differences accounted for most of the approval time differences (p < 0.001). Indications supported by overall survival benefit evidence had shorter median review time differences (145.0 days) than those without such evidence (235.0 days, p = 0.008). Indications with overall survival benefit evidence were 3.94 times more likely to be approved in China compared to those without such evidence (p = 0.001), controlling for approval year, cancer type, and the prevalence of cancer by site. Interpretation: FDA-approved cancer drug indications demonstrating a survival benefit were more likely to receive approvals in China with shorter regulatory review times compared to indications without such evidence. Given that manufacturer submission times were the main driver of cancer drug approval times in China, factors influencing submission timing should be explored. Funding: No funding.

Health care payments in the Asia Pacific: validation of five survey measures of economic burden.

INTRODUCTION: Many low and middle-income countries rely on out-of-pocket payments to help finance health care. These payments can pose financial hardships for households; valid measurement of this type of economic burden is therefore critical. This study examines the validity of five survey measures of economic burden caused by health care payments. METHODS: We analyzed 2002/03 World Health Survey household-level data from four Asia Pacific countries to assess the construct validity of five measures of economic burden due to health care payments: any health expenditure, health expenditure amount, catastrophic health expenditure, indebtedness, and impoverishment. We used generalized linear models to assess the correlations between these measures and other constructs with which they have expected associations, such as health care need, wealth, and risk protection. RESULTS: Measures of impoverishment and indebtedness most often correlated with health care need, wealth, and risk protection as expected. Having any health expenditure, a large health expenditure, or even a catastrophic health expenditure did not consistently predict degree of economic burden. CONCLUSIONS: Studies that examine economic burden attributable to health care payments should include measures of impoverishment and indebtedness.