Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study.

Objective To determine if drugs approved through the Food and Drug Administration's expedited development and review pathways have different rates of safety related label changes after approval compared with drugs approved through standard non-expedited pathways.Design Retrospective cohort study.Setting FDA public records, January 1997 to April 2016.Participants 382 FDA approved drugs.Main outcome measures The number of times a particular safety section of a label (boxed warning, contraindication, warning, precaution, or adverse reaction) was changed during a drug's time on the market. The relative rate of safety related label changes per year for expedited pathway and non-expedited pathway drugs was compared by forming matched pairs of drugs in the same therapeutic class that were approved within three years of each other.Results Among the 382 eligible new drugs, 135 (35%) were associated with an expedited development or review pathway, and matches were available for 96 (71%). The matched pairs were associated with a total of 1710 safety related label changes during the study period. Expedited pathway drugs were characterized by a rate of 0.94 safety related label changes for each drug per year, compared with 0.68 safety related label changes per year for non-expedited pathway drugs (rate ratio 1.38, 95% confidence interval 1.25 to 1.52). Compared with non-expedited pathway drugs, expedited pathway drugs had a 48% higher rate of changes to boxed warnings and contraindications, the two most clinically important categories of safety warnings (1.48, 95% confidence interval 1.07 to 2.06). A qualitative review of changes to the boxed warning sections revealed that less than 5% (3/67) were changed to describe reduced risks for patients.Conclusions Expedited development and regulatory review pathways can accelerate the availability of new drugs, but drugs approved through these pathways are associated with increased safety related label changes after approval, particularly for the types of changes representing the highest risk warnings. To inform appropriate policy interventions, additional research should explore the causal factors contributing to these different rates.

A New Golden Age? Proposal for an Innovative Global Health Funding Mechanism for Middle-Income Countries.

Despite economic growth and increased global commitment to health financing in the past decades, the health needs of some of the world's most vulnerable people remain overlooked. In particular, middle-income countries (MICs) often face the conundrum of receiving reduced development assistance for health (DAH) while still being home to most of the world's poor and the majority of the global burden. We believe that this reflects shortcomings in the global DAH system's architecture, which operate on principles that do not respond well to current realities. Hence, we propose a novel mechanism for international health financing and action that specifically addresses the newly emerged strengths and needs of MICs. The Incentives for Health (I4H) Alliance will offer MICs flexible incentives in exchange for their making and meeting health-related commitments in their countries. Countries can set their own health targets, in alignment with the existing Sustainable Development Goals' framework, and those that achieve them will be subsequently rewarded with financial or other incentives, which are not restricted to the health sector. We believe that the I4H Alliance will promote greater MIC involvement towards global health financing both as incentive providers and recipients; encourage collaboration between Ministries of Health and Finance; and provide a needed complement to traditional DAH mechanisms. We advocate for the creation of I4H at a MICs-oriented financing institution such as the New Development Bank. We intend I4H to spark new thinking around innovative health financing approaches to ensure that the "golden age" of global health remains ahead.