Precision oncology: the intention-to-treat analysis fallacy

Autor: Ryosuke Okamura, Jason K. Sicklick, Shumei Kato, Razelle Kurzrock
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Clinical Trials and Supportive Activities
Oncology and Carcinogenesis
Medical Oncology
Article
law.invention
03 medical and health sciences
0302 clinical medicine
Bias
Randomized controlled trial
Clinical Research
law
Neoplasms
Internal medicine
Humans
Medicine
False Positive Reactions
Molecular Targeted Therapy
Oncology & Carcinogenesis
Precision Medicine
Protein Kinase Inhibitors
Cancer
Randomized Controlled Trials as Topic
Response rate (survey)
Intention-to-treat analysis
business.industry
Confounding
Evaluation of treatments and therapeutic interventions
Precision oncology
Precision medicine
Intention to Treat Analysis
Clinical trial
Good Health and Well Being
Treatment Outcome
030104 developmental biology
Intention-to-treat
5.1 Pharmaceuticals
Research Design
6.1 Pharmaceuticals
030220 oncology & carcinogenesis
Public Health and Health Services
Biomarker (medicine)
Development of treatments and therapeutic interventions
business
Zdroj: Eur J Cancer
ISSN: 0959-8049
Popis: It has recently been suggested that precision oncology studies should be reanalysed using the intention-to-treat (ITT) methodology developed for randomized controlled clinical trials. This reanalysis dramatically decreases response rates in precision medicine studies. We contend that the ITT analysis of precision oncology trials is invalid. The ITT methodology was developed three decades ago to mitigate the problems of randomized trials, which try to ensure that both arms have an unselected patient population free from confounders. In contrast, precision oncology trials specifically select patients for confounders (that is biomarkers) that predict response. To demonstrate the issues inherent in an ITT reanalysis for precision cancer medicine studies, we take as an example the drug larotrectinib (TRK inhibitor) approved because of remarkable responses in malignancies harbouring NTRK fusions. Based on large-scale studies, NTRK fusions are found in ~0.31% of tumours. In a non-randomized pivotal study of larotrectinib, 75% of the 55 treated patients responded. Based upon the prevalence of NTRK fusions, ~18,000 patients would need to be screened to enrol the 55 treated patients. Utilizing the ITT methodology, the revised response rate to larotrectinib would be 0.23%. This is, of course, a dramatic underestimation of the efficacy of this now Food and Drug Administration (FDA)-approved drug. Similar issues can be shown for virtually any biomarker-based precision clinical trial. Therefore, retrofitting the ITT analysis developed for unselected patient populations in randomized trials yields misleading conclusions in precision medicine studies.
Databáze: OpenAIRE
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