ObjectiveTo review existing regulations and policies utilised by countries to enable patient access to orphan drugs.MethodsA review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country.ResultsFifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country’s legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country’s pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access.ConclusionsOverall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.

Objective To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people.Design Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends.Setting Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network.Participants Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million).Main outcome measures Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides.Results Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were −31.0% (95% confidence interval −33.0% to −29.0%) among adolescents, −24.3% (−25.4% to −23.2%) among young adults, and −14.5% (−16.0% to −12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100 000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, −6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100 000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group.Conclusions Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.

Introduction Most individuals make healthcare visits before suicide, but many do not have a diagnosed mental health condition. This study seeks to investigate suicide risk among patients with a range of physical health conditions in a U.S. general population sample and whether risk persists after adjustment for mental health and substance use diagnoses. Methods This study included 2,674 individuals who died by suicide between 2000 and 2013 along with 267,400 controls matched on year and location in a case-control study conducted in 2016 across eight Mental Health Research Network healthcare systems. A total of 19 physical health conditions were identified using diagnostic codes within the healthcare systems' Virtual Data Warehouse, including electronic health record and insurance claims data, during the year before index date. Results Seventeen physical health conditions were associated with increased suicide risk after adjustment for age and sex (p<0.001); nine associations persisted after additional adjustment for mental health and substance use diagnoses. Three conditions had a >twofold increased suicide risk, including traumatic brain injury (AOR=8.80, p<0.001), sleep disorders, and HIV/AIDS. Multimorbidity was present in 38% of cases versus 15.5% of controls, and represented nearly a twofold increased risk for suicide. Conclusions Although several individual conditions, such as traumatic brain injury, were associated with high risk of suicide, nearly all physical health conditions increased suicide risk, even after adjustment for potential confounders. In addition, having multiple physical health conditions increased suicide risk substantially. These data support suicide prevention based on the overall burden of physical health.