Strength of Evidence Underlying the CMS-FDA Parallel Review of Comprehensive Genomic Profiling Tests in the Cancer Setting.

BACKGROUND: Although use of comprehensive genomic profiling (CGP) was approved by a novel CMS/FDA parallel review process, the quality of the supporting evidence is unclear. We evaluated the rigor of the peer-reviewed literature cited in the National Coverage Determination Memorandum for the FoundationOne CDx (F1CDx). METHODS: We identified studies cited in the memorandum. Two independent researchers evaluated each study and applied a modified version of the Fryback and Thornbury hierarchy[1], an established framework for evaluating the efficacy of diagnostic tests. Studies focused on clinical outcomes were then categorized by study design, guided by recommendations from the Center for Medical Technology Policy. RESULTS: The sample included 113 scientific studies. The majority (n = 60, 53.1%) used CGP outside the course of clinical care, and there was significant heterogeneity in the cancer types assessed and sequencing depth. We found 8 (7.1%) studies that assessed whether clinical care had changed due to CGP testing, and 38 (33.6%) assessed clinical outcomes. After excluding studies that tested for five or fewer genomic alterations, 25 remained in the clinical outcomes sample: Of these, only one included a comparator group that did not receive CGP testing. Only four studies used F1CDx as the primary genomic test, none of which compared the outcomes of patients who did vs did not receive the F1CDx test. CONCLUSIONS: The findings indicate gaps in the supporting evidence for broad CGP use in patients with solid tumors. More rigorous studies that assess clinical utility would better inform the approval process for novel diagnostic tests.

Clinical Considerations for Children of Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual, and All Sexually and Gender Diverse Families.

The visibility of lesbian, gay, bisexual, transgender, queer, intersex, asexual, and all sexually and gender diverse (LGBTQIA+) families is growing. Anti-LGBTQIA+ rhetoric and actions continue to shape the public discourse, legislation, and health care. This article highlights unique challenges and strengths of children raised by LGBTQIA+ parents. Health care professionals should be cognizant of challenges and resiliencies these children experience in a normative society regarding gender identity, sexual orientation, and sex development. Clinicians can conduct inclusive and nonjudgmental family and social histories in welcoming practices, with careful consideration of unique familial dynamics these children may experience at home.

Reporting of Study Participant Demographic Characteristics and Demographic Representation in Premarketing and Postmarketing Studies of Novel Cancer Therapeutics.

Importance: Adequate representation of demographic subgroups in premarketing and postmarketing clinical studies is necessary for understanding the safety and efficacy associated with novel cancer therapeutics. Objective: To characterize and compare the reporting of demographic data and the representation of individuals by sex, age, and race in premarketing and postmarketing studies used by the Food and Drug Administration (FDA) to evaluate novel cancer therapeutics. Design, Setting, and Participants: In this cross-sectional study, premarketing and postmarketing studies for novel cancer therapeutics approved by the FDA from 2012 through 2016 were identified. Study demographic information was abstracted from publicly available sources, and US cancer population demographic data was abstracted from US Cancer Statistics. Analyses were conducted from February 25 through September 21, 2020. Main Outcomes and Measures: The percentages of trials reporting sex, age, and race/ethnicity were calculated, and participation to prevalence ratios (PPRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the US cancer population in each group. PPRs were constructed for premarketing and postmarketing studies and by cancer type. Underrepresentation was defined as PPR less than 0.8. Results: From 2012 through 2016, the FDA approved 45 cancer therapeutics. The study sample included 77 premarketing studies and 56 postmarketing studies. Postmarketing studies, compared with premarketing studies, were less likely to report patient sex (42 studies reporting [75.0%] vs 77 studies reporting [100%]; P < .001) and race (27 studies reporting [48.2%] vs 62 studies reporting [80.5%]; P < .001). Women were adequately represented in premarketing studies (mean [SD] PPR, 0.91; 95% CI, 0.90-0.91) and postmarketing studies (mean PPR, 1.00; 95% CI, 1.00-1.01). Although older adults and Black patients were underrepresented in premarketing studies (older adults: mean PPR, 0.73; 95% CI, 0.72-0.74; Black patients: mean PPR, 0.32; 95% CI, 0.31-0.32), these groups continued to be underrepresented in postmarketing studies (older adults: mean PPR, 0.75; 95% CI, 0.75-0.76; Black patients: mean PPR, 0.21; 95% CI, 0.21-0.21). Conclusions and Relevance: This study found that older adults and Black patients were underrepresented in postmarketing studies of novel cancer therapeutics to a similar degree that they were underrepresented in premarketing studies. These findings suggest that postmarketing studies are not associated with improvements to gaps in demographic representation present at the time of FDA approval.