An Industry Perspective on the use of Forced Degradation Studies to Assess Comparability of Biopharmaceuticals.

Forced degradation, also known as stress testing, is used throughout pharmaceutical development for many purposes including assessing the comparability of biopharmaceutical products according to ICH Guideline Q5E. These formal comparability studies, the results of which are submitted to health authorities, investigate potential impacts of manufacturing process changes on the quality, safety, and efficacy of the drug. Despite the wide use of forced degradation in comparability assessments, detailed guidance on the design and interpretation of such studies is scarce. The BioPhorum Development Group is an industry-wide consortium enabling networking and sharing of common practices for the development of biopharmaceuticals. The BioPhorum Development Group Forced Degradation Workstream recently conducted several group discussions and a benchmarking survey to understand current industry approaches for the use of forced degradation studies to assess comparability of protein-based biopharmaceuticals. The results provide insight into the design of forced degradation studies, analytical characterization and testing strategies, data evaluation criteria, as well as some considerations and differences for non-platform modalities (e.g., non-traditional mAbs). This article presents survey responses from several global companies of various sizes and provides an industry perspective and experience regarding the practicalities of using forced degradation to assess comparability.

Downstream funding success of early career researchers for resubmitted versus new applications: A matched cohort.

BACKGROUND: Early career researchers face a hypercompetitive funding environment. To help identify effective intervention strategies for early career researchers, we examined whether first-time NIH R01 applicants who resubmitted their original, unfunded R01 application were more successful at obtaining any R01 funding within 3 and 5 years than original, unfunded applicants who submitted new NIH applications, and we examined whether underrepresented minority (URM) applicants differentially benefited from resubmission. Our observational study is consistent with an NIH working group's recommendations to develop interventions to encourage resubmission. METHODS AND FINDINGS: First-time applicants with US medical school academic faculty appointments who submitted an unfunded R01 application between 2000-2014 yielded 4,789 discussed and 7,019 not discussed applications. We then created comparable groups of first-time R01 applicants (resubmitted original R01 application or submitted new NIH applications) using optimal full matching that included applicant and application characteristics. Primary and subgroup analyses used generalized mixed models with obtaining any NIH R01 funding within 3 and 5 years as the two outcomes. A gamma sensitivity analysis was performed. URM applicants represented 11% and 12% of discussed and not discussed applications, respectively. First-time R01 applicants resubmitting their original, unfunded R01 application were more successful obtaining R01 funding within 3 and 5 years than applicants submitting new applications-for both discussed and not discussed applications: discussed within 3 years (OR 4.17 [95 CI 3.53, 4.93]) and 5 years (3.33 [2.82-3.92]); and not discussed within 3 years (2.81 [2.52, 3.13]) and 5 years (2.47 [2.22-2.74]). URM applicants additionally benefited within 5 years for not discussed applications. CONCLUSIONS: Encouraging early career researchers applying as faculty at a school of medicine to resubmit R01 applications is a promising potential modifiable factor and intervention strategy. First-time R01 applicants who resubmitted their original, unfunded R01 application had log-odds of obtaining downstream R01 funding within 3 and 5 years 2-4 times higher than applicants who did not resubmit their original application and submitted new NIH applications instead. Findings held for both discussed and not discussed applications.

Associations of topic-specific peer review outcomes and institute and center award rates with funding disparities at the National Institutes of Health.

A previous report found an association of topic choice with race-based funding disparities among R01 applications submitted to the National Institutes of Health ('NIH') between 2011 and 2015. Applications submitted by African American or Black ('AAB') Principal Investigators ('PIs') skewed toward a small number of topics that were less likely to be funded (or 'awarded'). It was suggested that lower award rates may be related to topic-related biases of peer reviewers. However, the report did not account for differential funding ecologies among NIH Institutes and Centers ('ICs'). In a re-analysis, we find that 10% of 148 topics account for 50% of applications submitted by AAB PIs. These applications on 'AAB Preferred' topics were funded at lower rates, but peer review outcomes were similar. The lower rate of funding for these topics was primarily due to their assignment to ICs with lower award rates, not to peer-reviewer preferences.

Provider and patient burdens of obtaining oral anticancer medications.

Oral anticancer medications (OAMs) are frequently used to treat patients with cancer. Unlike intravenous chemotherapy, OAMs are covered by prescription drug plans. We examined barriers to initiation of OAMs in 116 patients with prostate or kidney cancer (149 unique prescriptions). We found that the median time from initial prescription to prior authorization was 3 days and the median time from initial prescription to patient receipt of drug was 12 days. Seventy-three percent of all prescriptions required 2 or more phone calls by clinic staff and 40% required 5 or more calls. Of 107 prescriptions with data available, 54% utilized financial assistance; these required significantly more phone calls (P = .0001) and led to a longer median time to drug obtainment (P = .003) compared with those that did not require financial assistance. In those prescriptions with both initial and final co-pay information available, the initial out-of-pocket mean and median co-pays were $1226.03 and $329.73, respectively, but these dropped to $124.57 and $25.00 after utilization of co-pay assistance programs, excluding those with a $0 final co-pay. These early observations suggest that a more efficient process for initiation of OAMs is needed.

Veterans' Location in Health Professional Shortage Areas: Implications for Access to Care and Workforce Supply.

OBJECTIVE: To describe the distribution of Veterans in areas of the United States where there are potentially inadequate supplies of health professionals, and to explore opportunities suggested by this distribution for fostering health workforce flexibility. DATA SOURCES: County-level data from the 2015-2016 Health Resources and Services Administration's (HRSA's) Area Health Resources Files (AHRF) were used to estimate Veteran populations in HRSA-designated health professional shortage areas (HPSAs). This information was then linked to 2015 VA health facility information from the Department of Veterans Affairs. STUDY DESIGN: Potential Veteran populations living in Shortage Area Counties with no VHA facilities were estimated, and the composition of these populations was explored by Census division and state. PRINCIPAL FINDINGS: Nationwide, approximately 24 percent of all Veterans and 23 percent of Veterans enrolled in VHA health care live in Shortage Area Counties. These estimates mask considerable variation across states. CONCLUSIONS: An examination of Veterans residing in Shortage Area Counties suggests extensive maldistribution of health services across the United States and the continued need to find ways to improve health care access for all Veterans. Effective avenues for doing so may include increasing health workforce flexibility through expansion of nurse practitioner scopes of practice.

What race and ethnicity measure in pharmacologic research.

Advances in genomic technology have put the utility of collecting racial and ethnic data into question. Some researchers are optimistic about the potential of moving toward "personalized medicine" by using a person's genome to administer medications. Genetics will not erase the importance of race and ethnicity because race and ethnicity do not measure genetic composition. Unlike genes, race and ethnicity are social constructs; 2 persons with identical genetic makeup may self-identify as being of different race or ethnic origin. Race and ethnic categories have been subject to change over time; a person's self-identification may vary according to the context, wording, and format of the question asked. Despite the fluid nature of the concept, self-identified race and ethnicity can capture something that genes cannot, namely, aspects of culture, behavior, diet, environment, and features of social status that commonly used measures of socioeconomic status, such as income, education, and occupation, cannot measure.