Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov;9(21):7888-7895.
doi: 10.1002/cam4.3390. Epub 2020 Sep 4.

Associations between safety, tolerability, and toxicity and the reporting of health-related quality of life in phase III randomized trials in common solid tumors

Ramy R Saleh  1 , Nicholas Meti  1 , Domen Ribnikar  2 , Hadar Goldvaser  3   4 , Alberto Ocana  5   6   7 , Arnoud J Templeton  8   9 , Bostjan Seruga  2 , Eitan Amir  1
Affiliations

Associations between safety, tolerability, and toxicity and the reporting of health-related quality of life in phase III randomized trials in common solid tumors

Ramy R Saleh et al. Cancer Med. 2020 Nov.

Abstract

Background: Anti-cancer drugs are approved typically on the basis of efficacy and safety as evaluated in phase III randomized trials (RCTs). Health-related quality of life (HRQoL) is a direct measure of patient benefit, but is under-reported. Here we explore associations with reporting of HRQoL data in phase III RCTs in common solid tumors.

Methods: We searched ClinicalTrials.gov to identify phase III RCTs evaluating new drugs in adults with advanced cancers that completed accrual between January 2005 and October 2016. Data on HRQoL, safety, and tolerability comprising treatment-related death, treatment discontinuation and commonly reported grade 3 or 4 adverse events (AEs) were extracted. Associations between these measures and reporting of HRQoL data were explored using logistic regression.

Results: Of 377 phase III RCTs identified initially, 143 studies were analysed and comprised 55% positive trials and 90% industry sponsored trials. HRQoL was listed as an endpoint in 59% trials; and of these, only 65% reported HRQoL data. There were higher odds of reporting HRQoL data for positive trials (OR 2.05, P = .04) and trials published in journals with higher impact factor (OR 1.35, P = .01). Reporting of HRQoL was not associated with treatment-related death (OR 1.25, P = .40) or treatment discontinuation (OR 1.12, P = .61), but was positively associated with dyspnea and dermatological adverse events.

Conclusions: HRQoL is reported in only two-thirds of RCTs that describe collecting such data. Reporting of HRQoL is associated with positive trial outcome and higher journal impact factor, but not associated with overall safety and tolerability of anti-cancer drugs.

Keywords: oncology; quality of life; randomized controlled trials; treatment toxicity.

PubMed Disclaimer

Conflict of interest statement

Dr Eitan Amir reports personal fees from Genentech/Roche, personal fees from Apobiologix, personal fees from Myriad Genetics, personal fees from Agendia, outside the submitted work. Dr Ramy Saleh reports personal fees from Roche, outside the submitted work. Dr Nicholas Meti reports personal fees from Novartis, outside the submitted work. Dr Domen Ribnikar reports personal fees from Novartis, outside the submitted work. Dr Hadar Goldvaser reports personal honorarium fees from Roche, Novartis, Pfizer and Oncotest, personal advisory consultation fees from Novartis, all outside the submitted work. Dr Alberto Ocana reports travel support from Merck, advisory consultation fees from Daichii‐Sankyo and Entrechem. Dr Arnoud J. Templeton reports personal fees from Astellas, MSD, and Sanofi. Consultancy fees were paid to his institution by BMS, Janssen, Sanofi, and Roche. Conference/travel support was received from Sanofi, Janssen, Ipsen, and Roche. Dr Bostjan Seruga reports personal honorarium fees from Astellas, Jansse, Novartis and Roche.

Figures

FIGURE 1
FIGURE 1
Flowchart of study selection. HRQoL, health‐related quality of life; RCT, Randomized controlled trial
FIGURE 2
FIGURE 2
Distribution of HRQoL reporting and outcomes among all eligible clinical trials. HRQoL, Health‐related quality of life
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Tannock IF, Amir E, Booth CM, et al. Relevance of randomised controlled trials in oncology. Lancet Oncol. 2016;17:e560‐e567. - PubMed
    1. Rock EP, Kennedy DL, Furness MH, Pierce WF, Pazdur R, Burke LB. Patient‐reported outcomes supporting anticancer product approvals. J Clin Oncol. 2007;25:5094‐5099. - PubMed
    1. Kluetz PG, O'Connor DJ, Soltys K. Incorporating the patient experience into regulatory decision making in the USA, Europe, and Canada. Lancet Oncol. 2018;19:e267‐e274. - PubMed
    1. Scoggins JF, Patrick DL. The use of patient‐reported outcomes instruments in registered clinical trials: evidence from ClinicalTrials.gov. Contemp Clin Trials. 2009;30:289‐292. - PMC - PubMed
    1. Vodicka E, Kim K, Devine EB, Gnanasakthy A, Scoggins JF, Patrick DL. Inclusion of patient‐reported outcome measures in registered clinical trials: evidence from ClinicalTrials.gov (2007–2013). Contemp Clin Trials. 2015;43:1‐9. - PubMed

Substances