Dataset Information

Incidence of Placebo Adverse Events in Randomized Clinical Trials of Targeted and Immunotherapy Cancer Drugs in the Adjuvant Setting: A Systematic Review and Meta-analysis.

ABSTRACT: Importance:Several reports have associated the placebo effect with objective response and improvement of a clinical condition in oncology, but only a few studies have analyzed the adverse events (AEs) in the placebo groups of the clinical trials. Objective:To determine the incidence of placebo AEs reported in randomized clinical trials of modern cancer drugs in the adjuvant setting. Data Sources:Based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, a systematic literature search of English-language publications from January 1, 2000, through April 15, 2018, was performed using MEDLINE (PubMed). The following search terms were used to retrieve all trials from the PubMed library: adjuvant, maintenance, consolidation, and placebo, in addition to specific cancer type-related keywords. Study Selection:A double-blind, randomized, placebo-controlled, phase 3 design was mandatory for study inclusion. Only studies enrolling patients who had undergone macroscopically complete resections were included. No other anticancer treatments in addition to placebo were allowed in the control group. Only trials involving a targeted therapy (tyrosine kinase, BRAF, or MEK inhibitors) or immunotherapy-related drugs were included. Trials using chemotherapy, interferon, and endocrine therapy were excluded. Two authors (D.H.E. and F.D.W.) independently reviewed the studies for inclusion. Data Extraction and Synthesis:Data were extracted by investigators, and random-effects meta-analysis was performed to estimate the proportion of grade 3 to 4 placebo AEs in the included studies. Main Outcomes and Measures:Incidence of grade 3 to 4 placebo AEs in the placebo groups. Results:Of 731 studies screened, 10 eligible trials were found including 4 tumor types (melanoma, non-small cell lung cancer, gastrointestinal stromal tumor, and renal cell carcinoma). Overall, 11?143 patients (6270 [56.3%] in the treatment group with mean [SD] age of 55.6 [4.2] years and 4873 patients [43.7%] in the placebo group with mean [SD] age of 55.9 [4.3] years) were included. The mean incidence of any-grade placebo AEs was 85.1% (95% CI, 79.2%-91.0%). The most frequent (mean [SD]) grade 3 to 4 placebo AEs in patients were hypertension (2.8% [2.2%]), fatigue (1.0% [0.9%]), and diarrhea (0.8% [0.6%]). The overall, random-effects pooled incidence of grade 3 to 4 placebo AEs was 18% (95% CI, 15%-21%), with a high level of heterogeneity (I2?=?86%). Frequency of grade 3 to 4 placebo AEs was found to be correlated in the treatment and placebo groups (??=?0.7; P?=?.03). Mean study drug discontinuation owing to placebo AEs was 3.9% (95% CI, 2.7%-5.2%). Conclusions and Relevance:Placebo administration was associated with a substantial incidence of grade 3 to 4 placebo AEs in modern cancer adjuvant trials. This finding should be considered by investigators, sponsors, regulatory authorities, and patient support groups.

SUBMITTER: Chacon MR

PROVIDER: S-EPMC6324542 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Incidence of Placebo Adverse Events in Randomized Clinical Trials of Targeted and Immunotherapy Cancer Drugs in the Adjuvant Setting: A Systematic Review and Meta-analysis.

Chacón Matías Rodrigo MR Enrico Diego Hernán DH Burton Jeannette J Waisberg Federico Daniel FD Videla Viviana Marina VM

JAMA network open 20181207 8

<h4>Importance</h4>Several reports have associated the placebo effect with objective response and improvement of a clinical condition in oncology, but only a few studies have analyzed the adverse events (AEs) in the placebo groups of the clinical trials.<h4>Objective</h4>To determine the incidence of placebo AEs reported in randomized clinical trials of modern cancer drugs in the adjuvant setting.<h4>Data sources</h4>Based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses ...[more]

PMID: 30646278

Similar Datasets

Project description:BackgroundFor safety assessment in clinical trials, adverse events (AEs) are reported for the drug under evaluation and compared with AEs in the placebo group. Little is known about the nature of the AEs associated with clinical trials of SARS-CoV-2 vaccines and the extent to which these can be traced to nocebo effects, where negative treatment-related expectations favor their occurrence.MethodsIn our systematic review, we compared the rates of solicited AEs in the active and placebo groups of SARS-CoV-2 vaccines approved by the Western pharmaceutical regulatory agencies.We implemented a search strategy to identify trial-III studies of SARS-CoV-2 vaccines through the PubMed database. We adopted the PRISMA Statement to perform the study selection and the data collection and identified three trial: two mRNA-based (38403 participants) and one adenovirus type (6736 participants).FindingsRelative risks showed that the occurrence of AEs reported in the vaccine groups was higher compared with the placebo groups. The most frequently AEs in both groups were fatigue, headache, local pain, as injection site reactions, and myalgia. In particular, for first doses in placebo recipients, fatigue was reported in 29% and 27% in BNT162b2 and mRNA-1273 groups, respectively, and in 21% of Ad26.COV2.S participants. Headache was reported in 27% in both mRNA groups and in 24% of Ad26.COV2.S recipients. Myalgia was reported in 10% and 14% in mRNA groups (BNT162b2 and mRNA-1273, respectively) and in 13% of Ad26.COV2.S participants. Local pain was reported in 12% and 17% in mRNA groups (BNT162b2 and mRNA-1273, respectively), and in 17% of Ad26.COV2.S recipients. These AEs are more common in the younger population and in the first dose of placebo recipients of the mRNA vaccines.InterpretationOur results are in agreement with the expectancy theory of nocebo effects and suggest that the AEs associated with COVID-19 vaccines may be related to the nocebo effect.FundingFondazione CRT - Cassa di Risparmio di Torino, IT (grant number 66346, "GAIA-MENTE" 2019).

Project description:BackgroundImmunotherapies and targeted therapies have drastically improved survival in metastatic melanoma, but they can cause a range of adverse events (AEs). Understanding the costs of these events would facilitate an accurate comparison of melanoma treatments.ObjectiveTo compare the costs and frequency of AEs associated with immunotherapy and with targeted therapy in elderly patients with metastatic melanoma.MethodsWe conducted a retrospective cohort study using Medicare claims data from 2011 to 2014. Patients included had to have ≥1 diagnoses of metastatic melanoma and ≥1 claims for an immunotherapy or targeted therapy. We compared the 30-day expenditures of patients with and without each AE using a generalized linear model to determine the incremental cost per AE in patients who received immunotherapy or targeted therapy. The baseline demographic and clinical differences were adjusted for using propensity score with inverse probability of treatment. We also compared the mean costs of AEs associated with immunotherapy and targeted therapy.ResultsA total of 844 patients were included in the study (mean age, 75 years; standard deviation, 14 years). The mean baseline Charlson Comorbidity Index score was 8.4, and 65% of the patients were male. The mean cost for AEs was highest for respiratory events (ie, $24,150). Gastrointestinal, respiratory, and hematologic AEs were more common in patients who received immunotherapy, whereas general and administration-site AEs and other AEs (eg, fatigue, infections, muscular weakness) were more frequent in patients who received targeted therapy. AE-related costs with immunotherapy were highest for gastrointestinal, respiratory, and pain-related AEs; AEs with targeted therapy were highest for cardiovascular and general and administration-site events.ConclusionThese findings suggest that incremental costs associated with treatment-related AEs among elderly patients with metastatic melanoma were substantial, but the risks for and costs of the various types of AEs differed by therapy. Understanding the risks for and costs of AEs associated with the various therapeutic options can inform treatment decision-making in elderly patients with metastatic melanoma.

Dataset Information

Incidence of Placebo Adverse Events in Randomized Clinical Trials of Targeted and Immunotherapy Cancer Drugs in the Adjuvant Setting: A Systematic Review and Meta-analysis.

Publications

Incidence of Placebo Adverse Events in Randomized Clinical Trials of Targeted and Immunotherapy Cancer Drugs in the Adjuvant Setting: A Systematic Review and Meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets