Use of the Development Core Safety Information in the assessment of expectedness of serious adverse events reported in oncology clinical trials

Safety monitoring and successful blinding are important features of randomized, blinded clinical trials. We report chamber- and protocol-related adverse events (AEs) for participants enrolled in two randomized, double-blind clinical trials of hyperbaric oxygen (HBO2) for persistent post-concussive symptoms clinicaltrials.gov identifiers NCT01306968, HOPPS, and NCT01611194, BIMA), as well as the success of maintaining the blind with a low-pressure sham control arm. In both studies, participants were randomized to receive HBO2 (1.5 atmospheres absolute, >99% oxygen) or sham chamber sessions (1.2 atmospheres absolute, room air). In 143 participants undergoing 4,245 chamber sessions, chamber-related adverse events were rare (1.1% in the HOPPS study, 2.2% in the BIMA study). Minor, non-limiting barotrauma was the most frequently reported. Rarely, some participants experienced headache with chamber sessions. No serious adverse events were associated with chamber sessions. An allocation questionnaire completed after intervention revealed that the sham control arm adequately protected the blind in both trials. Participants based allocation assumptions on symptom improvement or lack of symptom improvement and could not discern intervention arm by pressure, smell, taste, or gas flow.

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32 Quantifying the Prevalence of Frailty in Drug Trials and the Relationship with Serious Adverse Events

Age and Ageing ◽

10.1093/ageing/afab029.11 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

pp. i7-i11

Author(s):

P Hanlon ◽

E Butterly ◽

J Lewsey ◽

S Siebert ◽

F S Mair ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Disease Severity ◽

Negative Binomial ◽

Frailty Index ◽

Chronic Obstructive ◽

Drug Trials ◽

Phase 3 ◽

Serious Adverse Events ◽

Increased Risk

Abstract Introduction Frailty is common in clinical practice, but trials rarely report on participant frailty. Consequently, clinicians and guideline-developers assume frailty is largely absent from trials and have questioned the relevance of trial findings to frail people. Therefore, we examined frailty in phase 3/4 industry-sponsored clinical trials of pharmacological interventions for three exemplar conditions: type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), and chronic obstructive pulmonary disease (COPD). Methods We constructed a 40-item frailty index (FI) in 19 clinical trials (7 T2DM, 8 RA, 4 COPD, mean age 42–65 years) using individual-level participant data. Participants with a FI >0.24 were considered “frail”. Baseline disease severity was assessed using HbA1c for T2DM, Disease Activity Score-28 (DAS28) for RA, and % predicted FEV1 for COPD. Using generalised gamma regression, we modelled FI on age, sex and disease severity. In negative binomial regression we modelled serious adverse event rates on FI, and combined results for each index condition in a random-effects meta-analysis. Results All trials included frail participants: prevalence 7–21% in T2DM trials, 33–73% in RA trials, and 15–22% in COPD trials. Increased disease severity and female sex were associated with higher FI in all trials. Frailty was associated with age in T2DM and RA trials, but not in COPD. Across all trials, and after adjusting for age, sex, and disease severity, higher FI predicted increased risk of serious adverse events; the pooled incidence rate ratios (per 0.1-point increase in FI scale) were 1.46 (95% CI 1.21–1.75), 1.45 (1.13–1.87) and 1.99 (1.43–2.76) for T2DM, RA and COPD, respectively. Conclusion Frailty is identifiable and prevalent among middle aged and older participants in phase 3/4 drug trials and has clinically important safety implications. Trial data may be harnessed to better understand chronic disease management in people living with frailty.

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Diarrhea in Placebo Arms of Cancer Studies

Cancer Diagnosis & Prognosis ◽

10.21873/cdp.10050 ◽

2021 ◽

Vol 1 (5) ◽

pp. 379-385

Author(s):

BIRTE J. WOLFF ◽

JOHANNES E. WOLFF

Keyword(s):

Clinical Trials ◽

Literature Review ◽

Adverse Events ◽

Healthy Volunteers ◽

Cancer Prevention ◽

Cancer Patients ◽

Systematic Literature Review ◽

Oncology Clinical Trials ◽

Prevention Studies ◽

Cancer Studies

Background/Aim: Diarrhea is among the most common adverse events in early oncology clinical trials, and drug causality may be difficult to determine. Materials and Methods: This is a systematic literature review of placebo arms of randomized cancer trials. Results: Anemia was reported in 95 of 127 placebo monotherapy cohorts. Publications involving healthy volunteers and cancer prevention studies reported lower frequencies than those with cancer patients. The average reported frequency of diarrhea grade 1 or higher among studies in cancer patients was 15%. The maximal reported frequencies for grades 1, 2, 3, 4, 5 were 56, 24, 6, 2, and 0%, respectively. Conclusion: When higher diarrhea frequencies than those are observed in treatment arms of clinical trials, then drug causality is likely.

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Improving attribution of adverse events in oncology clinical trials

Cancer Treatment Reviews ◽

10.1016/j.ctrv.2019.04.004 ◽

2019 ◽

Vol 76 ◽

pp. 33-40 ◽

Cited By ~ 3

Author(s):

Goldy C. George ◽

Pedro C. Barata ◽

Alicyn Campbell ◽

Alice Chen ◽

Jorge E. Cortes ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Oncology Clinical Trials

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Early Stopping Rules in Clinical Trials Based on Sequential Monitoring of Serious Adverse Events

Medical Decision Making ◽

10.1177/0272989x08327332 ◽

2008 ◽

Vol 29 (3) ◽

pp. 343-350 ◽

Cited By ~ 7

Author(s):

A. Kramar ◽

C. Bascoul-Mollevi

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Stopping Rules ◽

Early Stopping ◽

Serious Adverse Events

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Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events: Methods for item selection in industry-sponsored oncology clinical trials

Clinical Trials ◽

10.1177/1740774518799985 ◽

2018 ◽

Vol 15 (6) ◽

pp. 616-623 ◽

Cited By ~ 7

Author(s):

Peter C Trask ◽

Amylou C Dueck ◽

Elisabeth Piault ◽

Alicyn Campbell

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Patient Reported Outcomes ◽

Selection Process ◽

Late Phase ◽

Relevant Information ◽

Specific Patient ◽

Patient Reported ◽

Oncology Clinical Trials ◽

The Common

As new cancer treatment regimens demonstrate increased potential to improve patients’ survival, more focus is directed toward the quality of that extension of life and to obtaining additional information from patients regarding their experience with treatment. The utility of capturing patient-reported treatment-related symptoms to complement traditional clinician-rated symptomatic adverse event reporting is well-documented. The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library aimed at capturing patient-reported symptoms to inform the patient perspective on a treatment’s tolerability. The U.S. Food and Drug Administration has recommended using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in clinical trials. A practical guideline is needed to inform a priori selection of specific Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items for use in any given industry-sponsored oncology clinical trial. Standardizing this selection process will foster systematic and consistent data collection as part of drug development and enhance our knowledge on how to use patient-relevant information as part of a treatment’s risk/benefit assessment. This article presents methods and consensus recommendations for selecting specific Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items to include in early-phase and late-phase oncology clinical trials.

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