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 |
Externí odkaz: |