Risk-Based Monitoring in Clinical Trials: 2021 Update.

Clinical trial quality depends on ensuring participant safety and data integrity, which require careful management throughout the trial lifecycle, from protocol development to final data analysis and submission. Recent developments-including new regulatory requirements, emerging technologies, and trial decentralization-have increased adoption of risk-based monitoring (RBM) and its parent framework, risk-based quality management (RBQM) in clinical trials. The Association of Clinical Research Organizations (ACRO), recognizing the growing importance of these approaches, initiated an ongoing RBM/RBQM landscape survey project in 2019 to track adoption of the eight functional components of RBQM. Here we present results from the third annual survey, which included data from 4889 clinical trials ongoing in 2021. At least one RBQM component was implemented in 88% of trials in the 2021 survey, compared with 77% in 2020 and 53% in 2019. The most frequently implemented components in 2021 were initial and ongoing risk assessments (80 and 78% of trials, respectively). Only 7% of RBQM trials were Phase IV, while the proportions of Phase I-III trials ranged 27-36%. Small trials (< 300 participants) accounted for 60% of those implementing RBQM. The therapeutic areas with the largest number of RBQM trials were oncology (38%), neurology (10%), and infectious diseases (9%). The 2021 survey confirmed a pattern of increasing RBM/RBQM adoption seen in earlier surveys, with risk assessments, which have broad regulatory support, driving RBQM growth; however, one area requiring further development is implementation of centralized monitoring combined with reductions in source data verification (SDV) and source data review (SDR).

Risk-Based Monitoring in Clinical Trials: Increased Adoption Throughout 2020.

With the emergence of new technologies for data collection, the continued impact of the COVID-19 pandemic, and the increasing number of partially or fully decentralized clinical trials (DCTs), the importance of risk-based monitoring (RBM) and the larger risk-based quality management (RBQM) framework in clinical trial management is increasing. RBM and RBQM focus on the detection of events or trends that impact trial quality in terms of participant safety and data integrity. In 2019, the Association of Clinical Research Organizations (ACRO) began a landscape survey of RBM/RBQM implementation in ongoing clinical trials. Initial results of this survey, representing full-year data for 2019, were reported previously. Here, we present full-year landscape data for 2020 drawn from 5,987 clinical trials ongoing at the end of 2020, including 908 new studies started that year. Of these trials, 77% implemented at least one RBM/RBQM component, an increase from 47% for studies ongoing at the end of 2019. We also observed increased implementation for three of the five RBM components included in the survey. Centralized monitoring decreased nominally in 2020 compared with 2019. Although the percentages of 2020 trials incorporating reduced source data verification (SDV) and reduced source data review (SDR) increased from 2019 to 2020, these numbers are still low considering the large percentage of trials implementing at least one RBQM component. In the current clinical trial landscape, as more DCTs are launched and new data collection technologies are implemented, there remains a pressing need for greater use of centralized monitoring coupled with reductions in SDR/SDV and, ultimately, greater adoption of RBM and RBQM.

Differences in IgG Antibody Responses following BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines.

Studies examining antibody responses by vaccine brand are lacking and may be informative for optimizing vaccine selection, dosage, and regimens. The purpose of this study is to assess IgG antibody responses following immunization with BNT162b2 (30 µg mRNA) and mRNA-1273 (100 µg mRNA) vaccines. A cohort of clinicians at a nonprofit organization is being assessed clinically and serologically following immunization with BNT162b2 or mRNA-1273. IgG responses were measured at the Remington Laboratory by an IgG assay against the SARS-CoV-2 spike protein-receptor binding domain. Mixed-effect linear (MEL) regression modeling was used to examine whether the SARS-CoV-2 IgG level differed by vaccine brand, dosage, or number of days since vaccination. Among 532 SARS-CoV-2 seronegative participants, 530 (99.6%) seroconverted with either vaccine. After adjustments for age and gender, MEL regression modeling revealed that the average IgG antibody level increased after the second dose compared to the first dose (P < 0.001). Overall, titers peaked at week 6 for both vaccines. Titers were significantly higher for the mRNA-1273 vaccine on days 14 to 20 (P < 0.05), 42 to 48 (P < 0.01), 70 to 76 (P < 0.05), and 77 to 83 (P < 0.05) and higher for the BNT162b2 vaccine on days 28 to 34 (P < 0.001). In two participants taking immunosuppressive drugs, the SARS-CoV-2 IgG antibody response remained negative. mRNA-1273 elicited higher IgG antibody responses than BNT162b2, possibly due to the higher S-protein delivery. Prospective clinical and serological follow-up of defined cohorts such as this may prove useful in determining antibody protection and whether differences in antibody kinetics between the vaccines have manufacturing relevance and clinical significance. IMPORTANCE SARS-CoV-2 vaccines using the mRNA platform have become one of the most powerful tools to overcome the COVID-19 pandemic. mRNA vaccines enable human cells to produce and present the virus spike protein to their immune system, leading to protection from severe illness. Two mRNA vaccines have been widely implemented, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech). We found that, following the second dose, spike protein antibodies were higher with mRNA-1273 than with BNT162b2. This is biologically plausible, since mRNA-1273 delivers a larger amount of mRNA (100 µg mRNA) than BNT162b2 (30 µg mRNA), which is translated into spike protein. This difference may need to be urgently translated into changes in the manufacturing process and dose regimens of these vaccines.

Increasing Community College Enrollment When Everything Says You Shouldn't

[...]the checklist sheet included a color-coding scheme going down the left-hand side of the document. Since the main administration building does not have a one-stop shop, attendees would need some help navigating the building. The team intended the checklist to go with the individual when they left the event. [...]it included important dates for the upcoming semester as well as the fee payment deadline. [...]the return on investment was $142.14 per dollar spent. [...]the college adapted the in-person event to a virtual one. Because of this shift, the team stretched the event out over several days, from April 28th through May 1st.