“When people come off study drugs, they on average feel worse and are doing worse than people who are on the study drug,” said Dr Cella, who was not involved in the FDA study.

Sensitivity analyses allow researchers to test how a range of possible values for missing data points would affect a study’s conclusions. But the FDA analysis found that clinical trials seldom include sensitivity analyses for PROs.

The FDA findings presented at ISOQOL point to the need for standardization. That means defining what specific PROs a clinical trial will measure as well as when and how those measurements will be collected, analyzed, and reported.  

“You need to plan everything. It’s actually much more difficult to do PRO analysis than it is to do survival analysis,” said Rasmus Blechingberg Friis, MD, a medical oncologist specializing in lung cancer at Denmark’s Aarhus University. “It’s very difficult to measure how people’s health and quality of life develops on a group level.”

Related Articles

There are already guidelines for how to collect PROs, however. In 2018, an international team of clinical trial stakeholders agreed to a PRO-specific extension to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT-PRO).5 The extension included 16 items designed to clarify a study’s specific PRO question, hypothesis, and measurement methods — typically through well-established PRO surveys. 

Similarly, in 2013, a PRO-specific extension to Consolidated Standards of Reporting Trials (CONSORT-PRO) offered guidelines on how to report PROs.6 Recommendations included reporting PROs both at baseline and after treatment and including measures of statistical confidence.

That leaves one missing piece — PRO analysis. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) Consortium has been working on guidelines for PRO analysis since 2016.7 The consortium’s report is currently posted as a preprint and has been accepted for publication in Lancet Oncology

 “If people would agree on a common set of analytic strategies, and people would begin to gain familiarity with the metrics involved and what they mean, it would help interpretation,” said Dr Gotay, who is a member of SISAQOL. “It’s a tiny bit like the Tower of Babel … and I think it would help to come up with common language.”

Disclosure: Carolyn Gotay and Paul Kluetz are both SISAQOL members.


  1. Vallejo J, Fiero M, Zhou J, Roydhouse J, Kluetz P, Sridhara R. FDA analysis: relationship between time-to-deterioration in cough, dyspnea, and/or pain in chest to clinical endpoints in non-small cell lung cancer (NSCLC) trials. Qual Life Res. 2019;28(Suppl 1):S56. Abstract B201.6
  2. Fiero M, Roydhouse J, Vallejo J, King-Kallimanis B, Kluetz P, Sridhara R. FDA overview of statistical analysis of patient-reported outcomes in lung cancer clinical trials approved between January 2008 and December 2017. Qual Life Res. 2019;28(Suppl 1):S57-S58. Abstract B201.9
  3. Gotay CC, Kawamoto CT, Bottomley A, Efficace F. The prognostic significance of patient-reported outcomes in cancer clinical trials. J Clin Oncol. 2008;26(8):1355-63.
  4. Fiero M, Royhouse J, Vallejo J, King-Kallimanis BL, Kluetz P, Sridhara R. US Food and Drug Administration review of statistical analysis of patient-reported outcomes in lung cancer clinical trials approved between January, 2008, and December, 2017. Lancet Oncol. 2019;20(10):e582-e589.
  5. Calvert M, Kyte D, Mercieca-bebber R, et al. Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension. JAMA. 2018;319(5):483-494.
  6. Calvert M, Blazeby J, Altman DG, et al. Reporting of patient-reported outcomes in randomized trials: the CONSORT PRO extension. JAMA. 2013;309(8):814-22.
  7. Bottomley A, Pe M, Sloan J, et al. Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards. Lancet Oncol. 2016;17(11):e510-e514.