A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials

被引:14
|
作者
Mukherjee, Som D. [1 ]
Coombes, Megan E. [1 ]
Levine, Mitch [2 ]
Cosby, Jarold [3 ]
Kowaleski, Brenda [1 ]
Arnold, Andrew [1 ]
机构
[1] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON L8V 5C2, Canada
[2] McMaster Univ, Ctr Evaluat Med, Hamilton, ON L8V 5C2, Canada
[3] Brock Univ, St Catharines, ON, Canada
关键词
Early phase clinical trials; Oncology; Causality attribution; Adverse events; DRUG-REACTIONS; PROBABILITY; ALGORITHM; GUIDELINES; JUDGMENT;
D O I
10.1007/s10637-010-9456-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Methods Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Findings Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Interpretation Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.
引用
收藏
页码:1013 / 1020
页数:8
相关论文
共 50 条
  • [1] A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials
    Som D. Mukherjee
    Megan E. Coombes
    Mitch Levine
    Jarold Cosby
    Brenda Kowaleski
    Andrew Arnold
    [J]. Investigational New Drugs, 2011, 29 : 1013 - 1020
  • [2] Improving attribution of adverse events in oncology clinical trials
    George, Goldy C.
    Barata, Pedro C.
    Campbell, Alicyn
    Chen, Alice
    Cortes, Jorge E.
    Hyman, David M.
    Jones, Lee
    Karagiannis, Thomas
    Klaar, Sigrid
    Le-Rademacher, Jennifer G.
    LoRusso, Patricia
    Mandrekar, Sumithra J.
    Merino, Diana M.
    Minasian, Lori M.
    Mitchell, Sandra A.
    Montez, Sandra
    O'Connor, Daniel J.
    Pettit, Syril
    Silk, Elaine
    Sloan, Jeff A.
    Stewart, Mark
    Takimoto, Chris H.
    Wong, Gilbert Y.
    Yap, Timothy A.
    Cleeland, Charles S.
    Hong, David S.
    [J]. CANCER TREATMENT REVIEWS, 2019, 76 : 33 - 40
  • [3] Clinical and economic burden of serious adverse events (SAEs) in an early phase trials unit
    Minchom, Anna Rachel
    Baikady, Bindumalini Rao
    Avaiya, Tejaskumar Laxmanbhai
    Kaye, Stanley B.
    Banerji, Udai
    De Bono, Johann S.
    Lopez, Juanita Suzanne
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (15)
  • [4] Sources of disagreement between investigator and sponsor in causality assessment of serious adverse events during academic clinical trials
    Bezin, J.
    Miremont-Salame, G.
    Razafimanantsoa, M.
    Moore, N.
    Haramburu, F.
    Gimbert, A.
    [J]. FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2014, 28 : 2 - 2
  • [6] Quantitative and qualitative evaluations of data of serious adverse events reported to the vigilance unit during clinical trials
    Aydin, D.
    Blanc, E.
    Nguon, M.
    Robinson, P.
    Bodenan, E.
    [J]. FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2019, 33 : 83 - 83
  • [7] Serious adverse events in healthy volunteers identified during clinical trials
    Coimbra Hurtado, Jimena
    [J]. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 2018, 123 : 48 - 48
  • [8] Sources of Disagreement between Investigator and Sponsor in Causality Assessment of Serious Adverse Events during Academic French Clinical Trials
    Bezin, J.
    Miremont-Salame, G.
    Razafimanantsoa, M.
    Salvo, F.
    Moore, N.
    Haramburu, F.
    Gimbert, A.
    [J]. DRUG SAFETY, 2014, 37 (10) : 851 - 851
  • [9] Serious adverse events in clinical trials with TAVR and SAVR
    Barth, U.
    [J]. HERZ, 2019, 44 (06) : 526 - 533
  • [10] A tool for assessing adverse events in phase I/II oncology clinical trials
    Coombes, M.
    Mukherjee, S.
    Kowaleski, B.
    Levine, M.
    Cosby, J.
    Arnold, A.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (18)