International Country-Level Trends, Factors, and Disparities in Compassionate Use Access to Unlicensed Products for Patients With Serious Medical Conditions

This cohort study examines the disparity in compassionate use access observed across countries and explores the key driving factors. Question What are the key factors associated with the significant disparity in compassionate use (CU) activity across countries? Findings In this cohort study of 31 711 CU requests received from 110 countries, the presence of CU regulations and their public availability, as well as local clinical trial activity, were positively associated with higher request rates. Despite generally free provision of unlicensed therapeutic products, there was an association between a country's economic development and its request activity for unlicensed compounds via CU. Meaning Existence and public availability of CU regulations and an increase in local clinical trial activity are modifiable country-level factors that could potentially facilitate patient access to novel lifesaving medicines. Importance Compassionate use (CU) is a treatment option for patients with serious or life-threatening medical conditions that provides access to locally unlicensed medications (generally free of charge) when all available treatment options have been exhausted and enrollment in a clinical trial is not possible. Objective To examine the disparity in CU access observed across countries and explore the key driving factors. Design, Settings, and Participants This study analyzed all Novartis CU requests (for individual/named patients and cohort programs) received between January 1, 2018, and December 31, 2020, and investigated selected country-specific factors for association with request activity. Data analysis was performed from February 2021 to February 2022. Main Outcomes and Measures Country-specific request activity was quantified using request counts and rates per million population and examined in stratified and multivariable analyses (negative-binomial regression) for association with the following covariates: existence of local CU regulations and their public availability, clinical trial activity, population size, and gross domestic product. Results During the 36-month observation period, 31 711 CU requests were received from 110 countries, 23 194 (73%) of which came from only 10 high-income countries. All high-income countries combined accounted for 27 612 (87%) of all requests, while lower-middle-income and low-income countries contributed only 1021 (3%). Of all requests, 29 870 (94%) were from countries with CU regulations made publicly available on the internet, and higher request activity was demonstrated in countries conducting more clinical trials. Presence and public availability of CU regulations, population size, gross domestic product, and clinical trial activity were independently associated with the CU request activity in multivariable analysis. Conclusions and Relevance In this cohort study analyzing Novartis CU requests over a 3-year period, existence and public availability of CU regulations and local clinical trial activity were positively associated with higher CU request rates. The analysis also identified an association between macroeconomic factors and CU request activity, despite the generally free provision of unlicensed therapeutic products. Similar analyses of other comparable experiences are needed to supplement these initial observations. Ultimately, better understanding of factors associated with CU request activity would translate into improved early access to novel lifesaving products for patients with unmet medical needs around the world.

Automated summary

The presence and public availability of compassionate use regulations, as well as an increase in local clinical trial activity, are associated with higher rates of compassionate use requests across countries. Despite the free provision of unlicensed therapeutic products, there is a correlation between a country's economic development and its request activity for unlicensed compounds via compassionate use.