title: How to report toxicity associated with targeted therapies?
abstract: In the era of personalized medicine, molecularly targeted therapies (MTT) have modified the outcome of some cancer types. The price of tumor control needs to be balanced with toxicity since these new therapies are administered continuously for several months or sometimes for several years. For cytotoxic drugs, the incidence of adverse event (AE) was traditionally reported as frequency and intensity. This simple measure is not sufficient to capture the recurrent nature and duration of AE. This paper presents two methods to better describe the toxicity burden across the time: prevalence and Q-TWiST.
  
  
  
  Limitation of worst-grade method and advantages of prevalence and Q-TWiST in the analysis of toxicity were illustrated using data from a phase II trial and a hypothetically simulated clinical trial.
  
  
  
  Prevalence integrates the recurrent nature of AE. Using prevalence, it is possible to obtain a time profile of AE. Q-TWiST method evaluates the weighted time spent in each health state and also considers the recurrent nature of side-effects in order to assess the 'risk-benefit' ratio of a treatment. When interpreting Q-TWiST results, it is necessary to take into account overall survival and progression-free survival and to define a clinically relevant difference according to the setting.
  
  
  
  The two methods presented here capture different effects. They are helpful for physicians in their treatment choice (balance benefit risk), to counsel patients and to optimize supportive care. In order to ensure consistency and provide critical information required for medical decision-making, it is important to encourage the use of alternative statistical methods in the analysis of toxicities associated with MTT.
  
  
  
  NCT00541008.
authors.affiliation: Department of Biostatistics, Institut Claudius Regaud, IUCT-O Toulouse, Toulouse.
authors.forename: B
authors.initials: B
authors.lastname: Cabarrou
authors.affiliation: Department of Biostatistics, Institut Paoli Calmette, Marseille.
authors.forename: J M
authors.initials: JM
authors.lastname: Boher
authors.affiliation: Department of Biostatistics.
authors.forename: E
authors.initials: E
authors.lastname: Bogart
authors.affiliation: Department of Biostatistics.
authors.forename: E
authors.initials: E
authors.lastname: Tresch-Bruneel
authors.affiliation: Department of Medical Oncology, Centre Oscar Lambret, Lille.
authors.forename: N
authors.initials: N
authors.lastname: Penel
authors.affiliation: Department of Medical Oncology, Bordeaux University Hospital, Bordeaux.
authors.forename: A
authors.initials: A
authors.lastname: Ravaud
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif.
authors.forename: B
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Research and Development Department, Unicancer, Paris.
authors.forename: C
authors.initials: C
authors.lastname: Mahier Ait-Oukhatar
authors.affiliation: Department of Medical Oncology, Institut Claudius Regaud, IUCT-O Toulouse, Toulouse, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Delord
authors.affiliation: Department of Medical Oncology, Institut Claudius Regaud, IUCT-O Toulouse, Toulouse, France.
authors.forename: H
authors.initials: H
authors.lastname: Roché
authors.affiliation: Department of Biostatistics, Institut Claudius Regaud, IUCT-O Toulouse, Toulouse filleron.thomas@iuct-oncopole.fr.
authors.forename: T
authors.initials: T
authors.lastname: Filleron
mesh_terms: D000066491:Clinical Decision-Making; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D057285:Precision Medicine; D011788:Quality of Life
keywords: Q-TWiST; prevalence; target therapy; toxicity analysis; worst grade