Patient-Centered Approach to Benefit–Risk Characterization Using Number Needed to Benefit and Number Needed to Harm: Advanced Non–Small-Cell Lung Cancer

Abstract

This work summarizes the benefit and risk of the results of clinical trials submitted to the US Food and Drug Administration of therapies for the treatment of non–small cell lung cancer (NSCLC) using number needed to benefit (NNB) and number needed to harm (NNH) metrics. NNB and NNH metrics have been reported as potentially being more patient centric and more intuitive to medical practitioners than more common metrics, such as the hazard ratio, and valuable to medical practitioners in complementing other metrics, such as the median time to event. This approach involved the characterization of efficacy and safety results in terms of NNB and NNH of 30 clinical trials in advanced NSCLC supporting US Food and Drug Administration approval decisions from 2003 to 2017. We assessed trends of NNB over time of treatment (eg, for programmed death 1 inhibitors) and variation of NNB across subpopulations (eg, characterized by epidermal growth factor receptor mutation, programmed death ligand 1 expression, Eastern Cooperative Oncology Group performance status, age, and extent of disease progression). Furthermore, the evolution of NNB of treatments for advanced NSCLC was charted from 2003 to 2017. Across subpopulations, NNB, on average, was 4 patients for approved targeted therapies in molecularly enriched populations, 11 patients for approved therapies in nonmolecularly enriched populations, and 23 patients for withdrawn or unapproved therapies. Furthermore, the NNB analysis showed variation for attributes of epidermal growth factor receptor mutations, level of programmed death 1 expression, Eastern Cooperative Oncology Group performance status, etc. When considering the best-case subpopulations and available drugs, the NNB frontier reduced from an estimated value of 7.7 in 2003 to an estimated value of 2.5 in 2017 at the estimated median overall survival—equal to 6 months—of an untreated patient.

Examining the Reliability of Confidence Intervals for the Number Needed to Treat: A Simulation Study

“…NNT değeri açısından bu durum, yeni tedavi kontrolü ile karşılaştırıldığında ne kadar az etkiliyse kontrole kıyasla yeni tedavinin daha etkili o lduğu kesinliği o kadar az olur şeklinde yorumlanabilir. 34 NNT, randomize veya gözlemsel bir çalışmada, basit bir hesaplamanın sonucu olarak tahmin edilebilir. Ancak kontrol grubu, tedavi grubu, tedavinin e tkinliği ve tedavinin herhangi bir yan etkisinin olup olmadığı gibi faktörlerin dikkate alınmaması, NNT'nin yorumlanmasında ve kullanılmasında ciddi hatalara yol açar.…”

Complete metabolic response following anaplastic lymphoma kinase (ALK) targeted therapy in a patient with adenocarcinoma of unknown primary with immunohistochemistry/fluorescence in situ hybridisation discordant ALK test results

“…4 With the rapid expansion of targeted therapy options for many patients with advanced carcinoma and the survival benefit conferred by these therapies, the need to identify oncogenic drivers is of ever-increasing importance. 5 Recently, the first ever international guidelines have been released for the use of NGS for patients presenting with advanced carcinoma and include the recommendation to consider NGS for patients presenting with CUP. 6…”