ClinicalTrials.gov for Facilitating Rapid Understanding of Potential Harms of New Drugs: The Case of Checkpoint Inhibitors

Yang, Annie; Baxi, Shrujal S.; Korenstein, Deborah

doi:10.1200/jop.2017.025114

Cited by 10 publications

(13 citation statements)

References 45 publications

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“…In clinical trials and observational studies of CIs, rates of musculoskeletal problems like arthralgia, myalgia and back pain have ranged widely, with rates of arthralgia as high as 43%. 34 35 While clinical trials of CIs may underestimate rates of musculoskeletal irAEs, 36 our study suggests that persistent musculoskeletal symptoms are moderately common in long-term survivors. While these symptoms were seldom reported as 'severe' on the PRO-CTCAE, the proportion of patients reporting at least some mobility problems on the EQ-5D-3L seemed to rise as patients survived longer after treatment (table 6).…”

Section: Open Accessmentioning

confidence: 80%

Quality of life in long-term survivors of advanced melanoma treated with checkpoint inhibitors

Mamoor

Postow

Baxi

et al. 2020

J Immunother Cancer

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BackgroundImmune checkpoint inhibitors (CIs) have revolutionized treatment of advanced melanoma, leading to an emerging population of long-term survivors. Survivors’ quality of life (QOL) and symptom burden are poorly understood. We set out to evaluate symptom burden and QOL in patients with advanced melanoma alive more than 1 year after initiating CI therapy.MethodsCross-sectional surveys, accompanied by chart review of patients with advanced melanoma treated with CIs at Memorial Sloan Kettering Cancer Center, completed therapy, and were alive >1 year after treatment initiation. Surveys were administered between February and August 2018. Surveys included: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, EuroQOL, items from Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events and Fatigue Severity Scale.ResultsWe included 90 patients. The most common CI regimens were ipilimumab plus nivolumab (53%) and pembrolizumab (41%); most patients (71%) were not treated in clinical trials. Median time from CI therapy initiation was 40 months and from last dose was 28 months. Fatigue was reported by 28%, with higher fatigue scores in women than men; 12% reported difficulty sleeping. Aching joints (17%) and muscles (12%) were fairly common. Level of functioning was generally high. Overall QOL was excellent though 40% reported ‘some or moderate’ problems with anxiety/depression and 31% with pain/discomfort.ConclusionsAfter CI therapy, long-surviving advanced melanoma patients commonly report fatigue but otherwise have moderate symptom burden and good QOL. Ensuring appropriate symptom management will optimize clinical outcomes for these patients.

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Section: Open Accessmentioning

confidence: 80%

Quality of life in long-term survivors of advanced melanoma treated with checkpoint inhibitors

Mamoor

Postow

Baxi

et al. 2020

J Immunother Cancer

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“…The evaluation of clinical trial registries is recommended by the Cochrane Handbook for Systematic Reviews of Interventions to limit the risk of publication bias and to extract results [ 13 , 14 ]. The importance of ClinicalTrials.gov in facilitating the rapid understanding of harms for newer drugs such as ICIs had been recognized by previous studies [ 37 ], which is why it was selected as an information source for the extraction and comparison of safety data reported from ICI clinical trials in this study. Despite all this, from the numerous review articles on irAEs from ICIs, [ 15 , 38 – 41 ] none have evaluated and compared safety results pertaining to irAEs from publications, clinical trial registries and regulatory documents so far.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, minimizing the effect of time as a variable on discrepancies noted between safety results extracted from three sources (publications, ClinicalTrials.gov and FDA package inserts) would have been even more far-fetched. (3) Finally, the FDA mandates no specific terminology for reporting AE data [ 37 , 44 ], which if anything, would only further add to the discrepancies identified in the reporting of safety results for ICIs, had FDA package inserts been added to the comparison.…”

Section: Discussionmentioning

confidence: 99%

The quality of reporting general safety parameters and immune-related adverse events in clinical trials of FDA-approved immune checkpoint inhibitors

et al. 2020

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Background While immune-checkpoint inhibitors (ICIs) have transformed the field of oncology for advanced-stage cancers, they can lead to serious immune toxicities. Several systematic reviews have evaluated the risk of immune-related adverse events (irAEs); however, most have focused on published articles without evaluating trial registries. The objective of this methodological review was to compare the quality of reporting of safety information and in particular, serious irAEs (irSAEs), in both publications and ClinicalTrials.gov for all current FDA-approved ICIs. Methods PubMed was searched to retrieve all published phase III randomized controlled trials (RCTs) evaluating ICIs. For each eligible trial, we searched for corresponding registration on ClinicalTrials.gov and extracted relevant safety data from both the publication and results posted on registry. We then compared the quality of reporting and the value of safety data between both sources. Results Of 42 eligible published trials, 34 had results posted on ClinicalTrials.gov. Considerable variability was noted in the reporting of safety in both sources. SAEs were reported for all trial results in ClinicalTrials.gov compared to 23.5% of publications. An overall incidence for irAEs and irSAEs was reported in 58.8 and 8.8% of publications respectively, compared to 11.8 and 5.9% in registry results. Comparing the value of specific irSAEs was not possible between the two sources in 32/34 trials either due to different reporting formats (61.8%) or data not being reported in one or both sources (32.4%). From the 2 studies with compatible irSAE format, only 1 had matching data in both sources. Conclusions The reporting of irAEs / irSAEs varies considerably in publications and registries, which outlines the importance of standardizing the terminologies and methodologies for reporting safety information relevant to ICIs.

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“…The evaluation of clinical trial registries is recommended by the Cochrane Handbook for Systematic Reviews of Interventions to limit the risk of publication bias and to extract results [13,14]. The importance of ClinicalTrials.gov in facilitating the rapid understanding of harms for newer drugs such as ICIs had been recognized by previous studies [37], which is why it was selected as an information source for the extraction and comparison of safety data reported from ICI clinical trials in this study. Despite all this, from the numerous review articles on irAEs from ICIs, [15,[38][39][40][41] none have evaluated and compared safety results pertaining to irAEs from publications, clinical trial registries and regulatory documents so far.…”

Section: Discussionmentioning

confidence: 99%

The quality of reporting general safety parameters and immune-related adverse events in clinical trials of FDA-approved immune checkpoint inhibitors

Karimian

Mavoungou

Salem³

et al. 2020

Preprint

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Background – While immune-checkpoint inhibitors (ICIs) have transformed the field of oncology for advanced-stage cancers, they can lead to serious immune toxicities. Several systematic reviews have evaluated the risk of immune-related adverse events (irAEs); however, most have focused on published articles without evaluating trial registries. The objective of this methodological review was to compare the quality of reporting of safety information and in particular, serious irAEs (irSAEs), in both publications and ClinicalTrials.gov for all current FDA-approved ICIs.Methods – PubMed was searched to retrieve all published phase III randomized controlled trials (RCTs) evaluating ICIs. For each eligible trial, we searched for corresponding registration on ClinicalTrials.gov and extracted relevant safety data from both the publication and results posted on registry. We then compared the quality of reporting and the value of safety data between both sources.Results – Of 42 eligible published trials, 34 had results posted on ClinicalTrials.gov. Considerable variability was noted in the reporting of safety in both sources. SAEs were reported for all trial results in ClinicalTrials.gov compared to 23.5% of publications. An overall incidence for irAEs and irSAEs was reported in 58.8% and 8.8% of publications respectively, compared to 11.8% and 5.9% in registry results. Comparing the value of specific irSAEs was not possible between the two sources in 32/34 trials either due to different reporting formats (61.8%) or data not being reported in one or both sources (32.4%). From the 2 studies with compatible irSAE format, only 1 had matching data in both sources.Conclusions – The reporting of irAEs / irSAEs varies considerably in publications and registries, which outlines the importance of standardizing the terminologies and methodologies for reporting safety information relevant to ICIs.

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ClinicalTrials.gov for Facilitating Rapid Understanding of Potential Harms of New Drugs: The Case of Checkpoint Inhibitors

Cited by 10 publications

References 45 publications

Quality of life in long-term survivors of advanced melanoma treated with checkpoint inhibitors

Quality of life in long-term survivors of advanced melanoma treated with checkpoint inhibitors

The quality of reporting general safety parameters and immune-related adverse events in clinical trials of FDA-approved immune checkpoint inhibitors

The quality of reporting general safety parameters and immune-related adverse events in clinical trials of FDA-approved immune checkpoint inhibitors

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