For a study, researchers sought to provide worldwide, consensus-based ethical norms for clinical research that are PRO-specific. The PRO ethical standards were created using the guideline development methodology used by the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network. A systematic review of the Ethical Considerations of PROs in clinical research was included. From their creation until March 2020, the databases MEDLINE (Ovid), Embase, AMED, and CINAHL were searched. The databases were searched using the terms patient-reported outcome and ethic. To assess eligibility, two reviewers independently completed title and abstract screening before the full-text screening. The SPIRIT-PRO Extension trial protocol suggestions reinforced the evaluation. Following that, a two-round international Delphi procedure (n=96 participants; May and August 2021) and an October 2021 consensus meeting (n=25 international participants) were convened. Prior to voting, participants in the consensus meeting were given a summary of the Delphi process outcomes as well as information on whether the items agreed with current ethical standards.

In the first round of the Delphi procedure, twenty-three items were considered: six appropriate candidate items from the systematic review and seventeen additional items taken from the SPIRIT-PRO Extension. Ninety-six worldwide participants voted on the significance of each item for inclusion in ethical standards, and 12 more items were proposed for inclusion in round 2 of the Delphi process (35 items in total). At the consensus meeting (n=25 participants), fourteen topics were suggested for inclusion. Participants in the consensus meeting agreed on the final text of the PRO ethical rules, with input from six other persons. Items included addressed PRO-specific ethical issues such as research rationale, objectives, eligibility requirements, PRO concepts and domains, PRO assessment schedules, sample size, PRO data monitoring, barriers to PRO completion, participant acceptability and burden, administration of PRO questionnaires for participants who are unable to self-report PRO data, input on PRO strategy by patient partners or members of the public, avoiding missing data, and dissemination. 

The PRO ethics guidelines offer advice on how to deal with ethical difficulties in PRO clinical trials. Addressing PRO clinical research ethical challenges has the ability to assure high-quality PRO data while reducing participant risk, burden, and damage and safeguarding participant and investigator welfare.