Demographic Diversity of Clinical Trials for Therapeutic Drug Products: A Systematic Review of Recently Published Articles, 2017-2022.

The US Food and Drug Administration (FDA) encourages the use of enrollment practices that will lead to clinical trials that reflect the population most likely to use the therapeutic product (drug or biologic), if approved. In doing so, the benefit-risk profile of the product may be assessed more completely and offer patients and their health care providers a better understanding of the drug profile and greater confidence in clinical trial results. The objective of this systematic review was to assess recent literature on the demographic diversity of clinical trial participants, describe the methods used in defining clinical trial diversity, and address knowledge gaps to enhance clinical trial diversity. Our literature search initially yielded 246 articles. After applying our eligibility criteria, we conducted a full-text review and analyzed the contents of the 28 remaining articles in our systematic review. Eleven (39%) of the 28 articles used a reference standard to compare the participation of populations in clinical trials to assess diversity. The majority of the 28 articles reported on adult participants; only 5 included pediatric populations. Most articles found that women and minority populations were underrepresented in clinical trials. Some articles proposed solutions to improve clinical trial diversity; however, several did not comment on clinical trial diversity. Despite a growing emphasis on demographic diversity in research, certain populations continue to be underrepresented in clinical trials. There is a need to standardize the definition of diversity in clinical trials. Future research into effective enrollment approaches and appropriate reference standards could improve demographic diversity.

Thrombocytopenia including immune thrombocytopenia after receipt of mRNA COVID-19 vaccines reported to the Vaccine Adverse Event Reporting System (VAERS).

BACKGROUND: The objective of this study is to assess cases of thrombocytopenia, including immune thrombocytopenia (ITP), reported to the Vaccine Adverse Event Reporting System (VAERS) following vaccination with mRNA COVID-19 vaccines. METHODS: This case-series study analyzed VAERS reports of thrombocytopenia after vaccination with Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine. RESULTS: Fifteen cases of thrombocytopenia were identified among 18,841,309 doses of Pfizer-BioNTech COVID-19 Vaccine and 13 cases among 16,260,102 doses of Moderna COVID-19 Vaccine. The reporting rate of thrombocytopenia was 0.80 per million doses for both vaccines. Based on an annual incidence rate of 3.3 ITP cases per 100,000 adults, the observed number of all thrombocytopenia cases, which includes ITP, following administration of mRNA COVID-19 vaccines is not greater than the number of ITP cases expected. CONCLUSIONS: The number of thrombocytopenia cases reported to VAERS does not suggest a safety concern attributable to mRNA COVID-19 vaccines at this time.

Complementary use of passive surveillance and Mini-Sentinel to better characterize hemolysis after immune globulin.

BACKGROUND: Hemolysis after intravenous immune globulins (IGIVs) is a known complication, but expanding indications and recent manufacturing changes warrant ongoing postmarketing surveillance. Characterization of post-IGIV hemolysis to date has been limited to small case series. STUDY DESIGN AND METHODS: We queried the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) from 2007 to 2014. All reported post-IGIV hemolysis cases were classified using a prespecified case definition and a case series analysis performed. We also conducted two assessments using FDA's Mini-Sentinel (MS) system to quantify the risk of hemolysis by six product indications and by IGIV formulation and evaluate the onset interval. RESULTS: A total of 109 FAERS cases met our definition. For cases with available information, 83% (66/80) received IGIV doses of at least 2 g/kg, 98.1% (51/52) had non-O blood group, and 75% (64/85) of events occurred within 4 days of IGIV exposure. We identified 313,045 treatment episodes and 337 post-IGIV hemolytic events in MS from 2006 to 2014, with 72% occurring within 2 days. Rates of hemolysis were highest among patients with Kawasaki disease (KD) and immune thrombocytopenia (ITP). The risk among patients receiving nonlyophilized products was 2.3 times higher than that in patients receiving lyophilized products. CONCLUSION: With the largest case series to date, FAERS data support that higher doses and non-O blood group are key risk factors. The incident rate of post-IGIV hemolysis is estimated at one per 1000 IGIV treatment episodes, with most occurring within 2 days of exposure. The risk is higher in patients with KD and ITP and after receipt of nonlyophilized IGIV.