Participant Recruitment From Low- and Middle-Income Countries for Pivotal Trials of Drugs Approved by the U.S. Food and Drug Administration : A Cross-Sectional Analysis.

BACKGROUND: Many participants in clinical trials supporting U.S. Food and Drug Administration (FDA) drug approvals are recruited from outside the United States, including from low- and middle-income countries (LMICs). Where participants are recruited for pivotal trials has implications for ethical research conduct and generalizability. OBJECTIVE: To describe LMIC recruitment for pivotal trials of newly approved drugs for cancer, neurologic disease, and cardiovascular disease. DESIGN: Cross-sectional analysis. SETTING: Pivotal trials of new cancer, cardiovascular, and neurologic drugs approved from 2012 to 2019 matched to ClinicalTrials.gov, FDA records, and publications. MEASUREMENTS: Host countries and available per country enrollments were extracted. The primary end point was the proportion of pivotal trials enrolling participants in LMICs. The secondary end point was the proportion of pivotal trial participants contributed by LMICs for each indication area. RESULTS: Data were obtained from 66 new drugs and 144 pivotal clinical trials. All cardiovascular approvals (12 drugs, 29 trials) and neurologic approvals (26 drugs, 54 trials) were analyzed, as well as a random sample of cancer approvals (28 of 85 drugs [33%]) matched to their pivotal trials (61 of 210 trials [29%]). Among the trials, 56% in cancer, 79% in cardiovascular disease, and 56% in neurology recruited from an LMIC. For multicountry trials, country-level enrollment figures were not available for 71 trials (55%). For those reporting per country enrollment, the percentage of participants recruited from LMICs was 8% for cancer trials, 36% for cardiovascular trials, and 17% for neurology trials. LIMITATIONS: The study was limited to FDA-approved drugs in 3 areas, including a sample of cancer drugs. Pivotal trials of nonapproved drugs or drugs for other indications were not captured. CONCLUSION: Most pivotal trials for FDA-approved drugs recruit from LMICs. Publications and FDA documents generally do not provide country-level data on recruitment. PRIMARY FUNDING SOURCE: None.

Does education about local vaccination rates and the importance of herd immunity change US parents' concern about measles?

It is unclear how broadly aware parents are of the concept of herd immunity and whether parents consider community benefits of vaccination when making decisions about their child's vaccinations. We aimed to determine whether educating parents about community-level benefits of measles, mumps, and rubella (MMR) vaccination and local vaccination rates would impact concern about their child's risk of measles and risk of a measles outbreak. We conducted an electronic survey among Minnesota parents of children aged 6-18 years in August 2016. We assessed baseline knowledge of herd immunity, asked participants to estimate MMR vaccination coverage in their county, and asked participants to estimate the minimum coverage needed to prevent measles outbreaks. We then delivered a short, educational intervention via the survey to inform participants about the benefits of herd immunity, the actual MMR vaccination coverage in their county, and that at least 95% MMR vaccination coverage is needed to prevent measles outbreaks. Pre- and post-intervention, participants were asked to report how concerned they were that their child might get measles. We used logistic regression models to assess factors associated with awareness of herd immunity, change in concern about one's child's measles risk, and overall concern for a measles outbreak. Among 493 participants, 67.8% were aware of herd immunity at baseline. Post-intervention, 40.2% (n = 198) of parents learned that MMR vaccination rates in their county were higher than they expected. All participants found out that their county MMR rates were lower than the measles herd immunity threshold of 95%. Overall, 27.0% (n = 133) of participants reported an increase in concern that their child might get measles after learning about local vaccination coverage and the coverage needed to achieve herd immunity. We found that our short, educational intervention aimed to increase awareness about herd immunity and local vaccination led to an increase in concern about disease risk among less than a third of parents.

Global assessment of national mandatory vaccination policies and consequences of non-compliance.

BACKGROUND: Declining vaccination coverage and increasing hesitancy is a worldwide concern. Many countries have implemented mandatory vaccination policies to promote vaccination. However, mandatory vaccination policies differ significantly by country. Beyond case studies, no comprehensive study has compared these policies or the penalties for non-compliance on a global scale. METHODS: We conducted extensive keyword, policy, and literature searches to identify mandatory national vaccination policies globally and develop a comprehensive database. A mandatory national vaccination policy was defined as a policy from a national authority that requires individuals to receive at least one vaccination based on age or to access a service. Two reviewers independently evaluated evidence for a mandate and whether non-compliance penalties were incorporated. We categorized penalties into four types, based on the nature of the penalty. These penalties impact an individual's financial, parental rights, educational (i.e., child's school entry and access), and liberty status. We rated the severity within each category. RESULTS: Of 193 countries investigated, 54% (n = 105) had evidence of a nationwide mandate as of December 2018. The frequency, types, and severity of penalties varied widely across all regions. We found that 59% (n = 62) of countries with national mandates defined at least one penalty for non-compliance with a vaccine mandate. Among those, educational penalties (i.e., limiting a child's entry or ongoing access to school) were the most common (69%; n = 43), with most countries with educational penalties refusing school enrollment until vaccination requirements are met (81%; n = 35). CONCLUSION: We undertook a comprehensive assessment of national mandatory vaccination policies and identified a diversity of penalties in place to promote compliance. Our results highlight the need to critically evaluate the implementation of non-compliance penalties in order to determine their effectiveness and to define best practices for sustaining high vaccination uptake worldwide.

'What have you HEARD about the HERD?' Does education about local influenza vaccination coverage and herd immunity affect willingness to vaccinate?

BACKGROUND: Vaccination protects individuals directly and communities indirectly by reducing transmission. We aimed to determine whether information about herd immunity and local vaccination coverage could change an individual's vaccination plans and concern about influenza. METHODS: We surveyed Minnesota residents ≥18 years during the 2016 Minnesota State Fair. Participants were asked to identify the definition of herd immunity, to report their history of and plans to receive influenza vaccine, to report their concern about influenza, and to estimate the reported influenza vaccination coverage in their county. After providing educational information about herd immunity and local vaccination rates, we reassessed vaccination plans and concerns. We used logistic regression to estimate predicted percentages for those willing to be vaccinated, for concern about influenza, and for changes in these outcomes after the intervention. We then compared those individuals with and without prior knowledge of herd immunity, accounting for other characteristics. RESULTS: Among 554 participants, the median age was 57 years; most were female (65.9%), white (91.0%), and non-Hispanic/Latino (93.9%). Overall, 37.2% of participants did not know about herd immunity and 75.6% thought that the influenza vaccination coverage in their county was higher than it was reported. Those not knowledgeable about herd immunity were significantly less likely than those knowledgeable about the concept to report plans to be vaccinated at baseline (67.8% versus 78.9%; p = 0.004). After learning about herd immunity and influenza vaccination coverage, the proportion of those not knowledgeable about herd immunity who were willing to be vaccinated increased significantly by 7.3 percentage points (p = 0.001). Educating participants eliminated the significant difference in the proportion planning to be vaccinated between these two groups (80.1% of those knowledgeable and 75.1% of those who were not initially knowledgeable became willing; p = 0.148). CONCLUSIONS: Education about herd immunity and local vaccination coverage could be a useful tool for increasing willingness to vaccinate, generating benefits both to individuals and communities.