Timing for First-in-Minor Clinical Trials of New Cancer Drugs.

OBJECTIVES: To describe the delay for first-in-minor cancer clinical trials and its relationship with the Food and Drug Administration (FDA) approval. STUDY DESIGN: We used ClinicalTrials.gov to create a sample of pediatric-relevant cancer drugs starting efficacy testing in adults from 2006 through 2011. We characterized the delay between first-in-adult efficacy trials and first-in-minor trials. We also assessed the proportion of drugs evaluated in minors that failed to gain approval, the proportions that were not evaluated in minors before receiving the FDA approval, and whether shorter delay was associated with larger effect sizes or greater probability of regulatory approval. RESULTS: Thirty-four percent of the 185 drugs in our cohort were evaluated in minors; the median delay to clinical trials was 4.16 years. Of all drugs, 17% received the FDA approval, 41% of which were never tested in minors before licensing. Of the 153 drugs not attaining approval, 78% were not evaluated in minors. Earlier testing did not significantly predict greater response rates (P = .13). Drugs not attaining regulatory approval were evaluated significantly earlier (3.0 for drugs not approved vs 5.4 years delayed testing for approved drugs, P = .019). CONCLUSIONS: New cancer drugs were typically evaluated in minors years after adult efficacy evaluation. This delay likely eliminated some drugs lacking desirable pharmacology before pediatric testing. However, some drugs that were eliminated may have had activity in pediatric indications. Approaches for prioritizing drugs for pediatric testing warrants further consideration.

Success rates for US and Canadian anticancer drug development efforts in pediatric oncology.

BACKGROUND: Approximately 5% of adult cancer interventions put into clinical testing attain regulatory approval. Little is known about corresponding rates for pediatric cancer. METHODS: Our primary outcomes were the proportion of interventions graduating to the next trial phase, randomized trials, and/or clinical practice. We created a saturation sample of clinical trials by searching ClinicalTrials.gov for all pediatric anticancer trials in the United States or Canada. Trial characteristics were extracted automatically from ClinicalTrials.gov records, and cancer indication/drug class categorization, biomarker enrichment, and Food and Drug Administration (FDA) approval status at time of recruitment were double-extracted from each record. Regulatory approval status and labeling modifications for each intervention were determined by searching Drugs@FDA and the New Pediatric Labeling Information Database. RESULTS: Five hundred eighty-nine pediatric trials launched between 1987 and 2019 were captured. The overall probability of graduation was 17.0%; 18.9% of interventions graduated from phase 1 to phase 2 trials, and 1.6% of interventions graduated from phase 2 to phase 3 trials. The proportion of interventions advancing from phase 1 to FDA approval was 3.6%, and 1.9% of interventions tested in phase 1 advanced to a randomized phase 2 trial. Only biomarker enrichment was significantly predictive of graduation from phase 1 to phase 2 trials (p = .011). CONCLUSION: The proportion of interventions advancing from phase 1 testing to FDA approval was similar to estimates for adult oncology. Our findings highlight the challenges for current paradigms of pediatric anticancer drug development.

Genetic discrimination views in online discussion forums: Perspectives from Canadian forumites.

Recent advancements in genetic technologies have made genetic information increasingly sought out in a wide range of non-therapeutic contexts, which has increased the risk that such information be used to discriminate against individuals. Frequently, it is genetic counselors who have to respond to questions about genetic discrimination (GD) from worried patients. Here, we examine the general Canadian public's knowledge, attitudes, and concerns about GD through a comprehensive analysis and categorization of posts from selected Canadian online discussion forums. Overall, we collected 1,638 posts, from which we coded 694 posts originating from newspaper comment sections and Reddit posts that were categorized to yield 6 main themes that consistently concerned Canadian users on the topics of GD: (a) discussions centered around how insurance business practices can be affected by genetic information; (b) issues in employment; (c) 'fear' of genetic testing and eugenics; (d) preventive approaches such as law and human rights instruments; (e) the predictive value and privacy that should be conferred to genetic information; and (f) other ethical issues. Overall, discussions addressed risk stratification models applied to genetic information and personal insurance underwriting. We find that many forum users (aka forumites) fear GD in insurance and employment, consider genetic information private, and strongly support different legal approaches to prevent GD. However, we find dissension among forumites that may represent different advocacy groups such as insurers and employers. From these important concerns and social conceptions, we discuss issues that should be taken into consideration for the development of future policies and information campaigns addressing GD in Canada and other countries.

Probability of Success and Timelines for the Development of Vaccines for Emerging and Reemerged Viral Infectious Diseases.

BACKGROUND: Anticipated success rates and timelines for COVID-19 vaccine development vary. Recent experience with developing and testing viral vaccine candidates can inform expectations regarding the development of safe and effective vaccines. OBJECTIVE: To estimate timelines and probabilities of success for recent vaccine candidates. DESIGN: ClinicalTrials.gov was searched to identify trials testing viral vaccines that had not advanced to phase 2 before 2005, and the progress of each vaccine from phase 1 through to U.S. Food and Drug Administration (FDA) licensure was tracked. Trial characteristics were double-coded. (Registration: Open Science Framework [https://osf.io/dmuzx/]). SETTING: Trials launched between January 2005 and March 2020. PARTICIPANTS: Preventive viral vaccine candidates for 23 emerging or reemerged viral infectious diseases. MEASUREMENTS: The primary end point was the probability of vaccines advancing from launch of phase 2 to FDA licensure within 10 years. RESULTS: In total, 606 clinical trials forming 220 distinct development trajectories (267 343 enrolled participants) were identified. The probability of vaccines progressing from phase 2 to licensure within 10 years was 10.0% (95% CI, 2.6% to 16.9%), with most approvals representing H1N1 or H5N1 vaccines. The average timeline from phase 2 to approval was 4.4 years (range, 6.4 weeks to 13.9 years). The probabilities of advancing from phase 1 to 2, phase 2 to 3, and phase 3 to licensure within the total available follow-up time were 38.2% (CI, 30.7% to 45.0%), 38.3% (CI, 23.1% to 50.5%), and 61.1% (CI, 3.7% to 84.3%), respectively. LIMITATIONS: The study did not account for preclinical development and relied primarily on ClinicalTrials.gov and FDA resources. Success probabilities do not capture the varied reasons why vaccines fail to advance to regulatory approval. CONCLUSION: Success probabilities and timelines varied widely across different vaccine types and diseases. If a SARS-CoV-2 vaccine is licensed within 18 months of the start of the pandemic, it will mark an unprecedented achievement for noninfluenza viral vaccine development. PRIMARY FUNDING SOURCE: McGill Interdisciplinary Initiative in Infection and Immunity (MI4) Emergency COVID-19 Research Funding program.