Consensus on Language for Advance Informed Consent in Health Care-Associated Pneumonia Clinical Trials Using a Delphi Process

Abstract

Importance: Information to be included in advance informed consent forms for health care-associated pneumonia treatment trials remains to be determined.

Objective: To identify and determine how to describe information to be included in an advance informed consent form for an early-enrollment noninferiority hospital-acquired and/or ventilator-associated bacterial pneumonia (HABP/VABP) clinical trial.

Design, setting, and participants: A Delphi consensus process with stakeholders in HABP/VABP clinical trials was conducted using qualitative semistructured telephone interviews from June to August 2016, followed by 2 online surveys, the first from April to May 2017, and the second from September to October 2017. All stakeholders who participated in the interview were invited to participate in the first survey. Stakeholders who participated in the first survey were invited to participate in the second survey. Stakeholders were patients at risk of pneumonia, caregivers, representatives of institutional review boards, investigators, and study coordinators.

Main outcomes and measures: Description and consensus of information to be included in advance informed consent forms for early enrollment in noninferiority HABP/VABP clinical trials.

Results: Suggestions from 52 stakeholders about what key informed consent concepts to include and how to explain them were used to create 3 categories to be included in an advance consent form: (1) reassurances on patient health and treatment, (2) rationale for advance consent and early enrollment, and (3) an explanation of noninferiority. At the end of the Delphi process, at least 80% consensus was reached among the 40 stakeholders who participated in the second online survey on each of the statements to include in the proposed consent text. Throughout the process, however, describing and reaching consensus on statements about noninferiority was more problematic than the other categories.

Conclusions and relevance: The stakeholders endorsed consent language to be used in combination with a strategy for enrolling patients at highest risk for pneumonia before infection onset. Data-driven consent language may help potential participants make informed decisions about their involvement in clinical research and improve enrollment rates, which are necessary to evaluate new treatments and improve patient care. The proposed consent language may be adapted for other trials using an early enrollment strategy and for noninferiority trials.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Powers reports consulting for Corbus, Eli Lilly, Fuji, Gilead, Johnson & Johnson, Microbion, Otsuka, and Romark. Dr Fowler reports personal fees from Novartis, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Basilea, Affinergy, Janssen, xBiotech, Contrafect, Regeneron, Basilea, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, grants from NIH, MedImmune, Cerexa/Forest/Actavis/Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Cubist/Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius; Genentech, Regeneron, Basilea, Janssen, from Green Cross, Cubist, Cerexa, Durata, Theravance; Debiopharm, Royalties from UpToDate; personal fees from Arrevus, DaVolterra, Eicos, GlaxoSmithKline, and Shinogi outside the submitted work; and a patent sepsis diagnostics pending. Dr Holland reports consulting for Basilea Pharmaceutica, Motif Bio, Genentech, and Theravance; and serving on a scientific advisory board for Motif Bio. Dr Calvert reported grants from U.S. FDA and other from CTTI Member Organizations during the conduct of the study. Dr Swezey reported grants from U.S. Food and Drug Administration and other from Annual fees from CTTI Member Organizations during the conduct of the study. Dr Collyar reported personal fees from CTTI during the conduct of the study; personal fees and non-financial support from Parexel, personal fees and non-financial support from Merck, non-financial support from Voz Advisors, personal fees and non-financial support from M2GEN, non-financial support from McKinsey & Associates, personal fees from BridgeBio, non-financial support from Boehringer Ingelheim, other support from Novartis, Janssen, Takeda, Incyte, and Odonate; and personal fees and nonfinancial support from IQVIA and nonfinancial support from TrialScope outside the submitted work. Dr De Anda reported other support from Merck & Co, Inc, during the conduct of the study, and from Merck & Co, Inc outside the submitted work. Dr Holland reported other support from Clinical Trials Transformation Initiative during the conduct of the study; personal fees from Basilea Pharmaceutica, Genentech, Motif Bio, Theravance, and Roivant Sciences outside the submitted work. No other disclosures were reported.