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JAMA Intern Med. 2018 Dec 1;178(12):1586-1596. doi: 10.1001/jamainternmed.2018.4710.

Evaluating Progression-Free Survival as a Surrogate Outcome for Health-Related Quality of Life in Oncology: A Systematic Review and Quantitative Analysis.

Author information

1
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
2
Alberta PROMs & EQ-5D Research & Support Unit, School of Public Health, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada.
3
Department of Diagnostic Radiology, University of Toronto, Toronto, Ontario, Canada.
4
Department of General Surgery, Université de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada.
5
2nd Department of General Surgery, Jagiellonian University Medical College, Krakow, Poland.
6
Centre for Research, Training and Innovation in Surgery (CERTAIN Surgery), Krakow, Poland.
7
Department of General Medicine, Kurashiki Central Hospital, Miwa Kurashiki Okayama, Japan.
8
High Institute of Public Health, Alexandria University, Al Ibrahimeyah Qebli WA Al Hadrah Bahri Qesm Bab Sharqi, Alexandria Governorate, Egypt.
9
Drug Information Center, Tanta Chest Hospital, Ministry of Health, Tanta, Egypt.
10
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
11
Department of Surgery, Okinawa Prefectural Nanbu Medical Center & Children's Medical Center, Haebaru-cho, Shimajiri-gun, Okinawa, Japan.
12
Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto, Japan.
13
Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
14
Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
15
Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
16
Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada.
17
Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Huangpu District, Shanghai, People's Republic of China.
18
Accident and Emergency Department, Queen Mary Hospital, High West, Hong Kong.
19
Research Ethics in Medicine Study Group (REMEDY), Department of Philosophy and Bioethics, Jagiellonian University Medical College, Krakow, Poland.
20
Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, India.
21
Health Sciences Library, McMaster University, Hamilton, Ontario, Canada.
22
Biostatistics Unit/FSORC, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
23
Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada.
24
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
25
Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.
26
Kingston Health Sciences Centre, Cancer Centre of Southeastern Ontario, Kingston General Hospital, Kingston, Ontario, Canada.
27
Cancer Research Institute, Queen's University at Kingston, Kingston, Ontario, Canada.
28
Centre for Health Economics and Policy Analysis, McMaster University, Hamilton, Ontario, Canada.
29
Programs for Health Economics and Outcome Measures, Hamilton, Ontario, Canada.

Abstract

Importance:

Progression-free survival (PFS) has become a commonly used outcome to assess the efficacy of new cancer drugs. However, it is not clear if delay in progression leads to improved quality of life with or without overall survival benefit.

Objective:

To evaluate the association between PFS and health-related quality of life (HRQoL) in oncology through a systematic review and quantitative analysis of published randomized clinical trials. Eligible trials addressed oral, intravenous, intraperitoneal, or intrapleural chemotherapy or biological treatments, and reported PFS or health-related quality of life.

Data Sources:

For this systematic review and quantitative analysis of randomized clinical trials of patients with cancer, we searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 2000, through May 4, 2016.

Study Selection:

Paired reviewers independently screened citations, extracted data, and assessed risk of bias of included studies.

Data Extraction and Synthesis:

We examined the association of difference in median PFS duration (in months) between treatment groups with difference in global, physical, and emotional HRQoL scores between groups (standardized to a range of 0-100, with higher scores representing better HRQoL) using weighted simple regressions.

Main Outcome and Measure:

The association between PFS duration and HRQoL.

Results:

Of 35 960 records screened, 52 articles reporting on 38 randomized clinical trials involving 13 979 patients across 12 cancer types using 6 different HRQoL instruments were included. The mean (SD) difference in median PFS between the intervention and the control arms was 1.91 (3.35) months. The mean (SD) differences in change of HRQoL adjusted to per-month values were -0.39 (3.59) for the global domain, 0.26 (5.56) for the physical domain, and 1.08 (3.49) for the emotional domain. The slope of the association between the difference in median PFS and the difference in change for global HRQoL (n = 30 trials) was 0.12 (95% CI, -0.27 to 0.52); for physical HRQoL (n = 20 trials) it was -0.20 (95% CI, -0.62 to 0.23); and for emotional HRQoL (n = 13 trials) it was 0.78 (95% CI, -0.05 to 1.60).

Conclusions and Relevance:

We failed to find a significant association between PFS and HRQoL in cancer clinical trials. These findings raise questions regarding the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer. Therefore, to ensure that patients are truly obtaining important benefit from cancer therapies, clinical trial investigators should measure HRQoL directly and accurately, ensuring adequate duration and follow-up.

PMID:
30285081
PMCID:
PMC6583599
[Available on 2019-10-01]
DOI:
10.1001/jamainternmed.2018.4710

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