Pivotal Trial Demographic Representation and Clinical Development Times for Oncology Therapeutics.

This study evaluates whether FDA-approved novel cancer therapeutics supported by pivotal trials with adequate representation of minoritized groups were associated with slower clinical development times than those with inadequate representation.

Transparency of Results Reporting in Cancer Clinical Trials.

This cross-sectional study investigates rates of results reporting among oncology clinical trials across trial registries, medical journals, and medical conferences.

Clinical Trial Diversity-Will We Know It When We See It?

This Editorial discusses the existing policy efforts in the US for ensuring adequate racial and ethnic diversity in clinical trials, identifies barriers to consistency and acceptable representation, and suggests measures to address them.

Implementation of 21st Century Cures Act Expanded Access Policies Requirements.

The US Food and Drug Administration (FDA) expanded access pathway allows patients with life-threatening or serious conditions to access investigational drugs outside of trials, under certain conditions. The 21st Century Cures Act ("Cures Act") requires certain drug companies to publicly disclose their expanded access policies. We characterized the proportion of applicable US biopharmaceutical companies, with an oncology related drug, implementing Cures Act requirements for expanded access policies and whether available policies contain the information described in the Act. We found about one-third of applicable biopharmaceutical companies (32%, 140/423) implemented the Cures Act requirement to have a public expanded access policy. Less than one-third of public policies contained all described information (31%, 44/140). Larger companies and those with at least one drug receiving an FDA expedited designation (59% vs. 21%; P < 0.001), or at least one FDA-approved drug (57% vs. 28%; P < 0.001) were more likely to have a public policy. Our results suggest the Cures Act may be having a limited impact on its goals of supporting timely medical decisions and closing informational gaps for patients and doctors around expanded access to investigational oncology therapies, especially for products sponsored by smaller and newer companies.

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.

Delays in the Publication of Important Clinical Trial Findings in Oncology.

Importance: The complete and timely dissemination of clinical trial data is essential to all fields of medicine, with delayed or incomplete data release having potentially deleterious effects on both patient care and scientific inquiry. While prior analyses have noted a substantial lag in the reporting of final clinical study results, we sought to refine these observations through use of a novel starting point for the measurement of dissemination delays: the date of a corporate press release regarding a phase 3 study's results. Objective: To measure the length of time elapsed between when a sponsor had results of study findings they deemed important to announce, and when the medical community had access to them. Design and Setting: Covering the years 2011 through 2016, we measured the delay from when 8 large pharmaceutical companies issued a press release announcing completed analyses of phase 3 clinical trials in oncology, and the public sharing of those results either on ClinicalTrials.gov or in a peer-reviewed biomedical journal as found via PubMed or Google Scholar. Press releases announcing regulatory steps and presentation schedules for conferences were excluded, as were those announcing results from preclinical trials, follow-up analyses, and studies of supportive care therapies or various modes of infusion for the same therapy. Main Outcomes and Measures: Time to public dissemination of clinical trial data. Results: Of the 100 press releases in our sample, 70 (70%) reported positive results, but only 31 (31%) included the magnitude of study findings. Through the end of follow-up, 99 (99%) of press releases had an associated peer-reviewed publication, complete data posting to ClinicalTrials.gov, or both, with a median time to reporting of 300 days (95% CI, 263-348 days). Positive findings were reported more quickly than negative ones (median of 272; 95% CI, 211-318 days vs 407; 95% CI, 298-705 days; log-rank P < .001). Conclusions and Relevance: Even for the most pressing study findings, median publication delays approach 1 year. As publication delays hinder research progress and advancements in clinical care, policies that enable early preprint release or public posting of completed data analysis should be pursued.

Availability of Investigational Medicines Through the US Food and Drug Administration's Expanded Access and Compassionate Use Programs.

Importance: The Right to Try Act of 2017 allows patients with life-threatening conditions to access investigational medicines outside clinical trials without oversight from the US Food and Drug Administration (FDA). A better understanding of existing expanded access programs can inform the consideration and implementation of both the federal Right to Try Act and state right-to-try laws. Objective: To determine the timing and duration of expanded access programs for investigational medicines initiated prior to FDA approval. Design and Setting: This cross-sectional study examined expanded access and compassionate use programs registered through August 1, 2017, identified from ClinicalTrials.gov and publicly available FDA documents. Main Outcomes and Measures: Start date of each program and 3 key regulatory dates (investigational new drug application activation, initial new drug application submission, and FDA approval), and timing and duration of expanded access availability in relation to new drug application submission and FDA approval. Results: Through ClinicalTrials.gov, 92 FDA-approved drugs and biologics with associated expanded access programs initiated prior to FDA approval were identified. These programs were initiated between September 1996 and June 2017 for medicines that were most commonly used to treat cancer (n = 46 [50.0%]); metabolic, endocrine, and genetic diseases (n = 16 [17.4%]); and infectious diseases (n = 14 [15.2%]). The median (interquartile range) premarket expanded access availability was 10.0 (6.0-19.5) months, constituting a median (interquartile range) of 14% (7%-25%) of the premarket clinical development period (investigational new drug application activation to FDA approval). Of 92 expanded access programs, 64 (69.6%) were initiated just before or after new drug application submission: 24 (26.1%) were initiated during the 6-month period before, and 40 (43.5%) in the 6 months after. Conclusions and Relevance: Over the past 2 decades, expanded access programs have provided access to investigational medicines for which evidence of safety and effectiveness was established. For medicines that ultimately receive FDA approval, these findings suggest that the FDA and pharmaceutical industry have established a balance between investigational new drug access and protection of patients from therapies without established safety. This balance may be compromised by policy makers seeking to speed access to investigational medicines through the Right to Try Act.

Characterizing expanded access and compassionate use programs for experimental drugs.

OBJECTIVE: We sought to determine the characteristics of "expanded access" and "compassionate use" programs registered in ClinicalTrials.gov and to determine the percentage of drugs provided through these programs that ultimately received FDA marketing approval. RESULTS: We identified 398 expanded access and compassionate use programs (hereafter referred to as expanded access programs) registered on ClinicalTrials.gov. Industry funded 61% (n = 241) of programs individually or collaboratively, while NIH and the US Federal Government rarely funded programs (3% [n = 11] and 2% [n = 6], respectively). Most programs provided access to drugs (71% [n = 282]), 11% to biologics (n = 43), and 10% to medical devices (n = 40). These programs covered 460 unique conditions, the most common being HIV (n = 26), leukemia (22), and multiple myeloma (n = 14). Only 2% of programs reported results in ClinicalTrials.gov. Most programs (82%) were open to enrolling adults and seniors (n = 326). These programs provided access to 210 unique experimental drugs, of which 76% have received FDA approval.