The modified Delphi method we employed required an expert panel that included researchers from each of two relevant fields: informed consent for genetic testing and AD biomarkers with a focus on amyloid imaging in humans. To assure that individuals recruited for the expert panel were chosen using objective criteria, a version of the knowledge resource nomination method based on a strategic literature search was employed . The study required that experts be willing to participate in a three-stage Delphi process.
The strategic literature search sought experts in informed consent for genetic testing and AD biomarkers with a focus on amyloid imaging in humans. The need for experts in amyloid imaging is self-evident. We sought experts in informed consent for genetic testing because amyloid imaging in clinically normal individuals is analogous to a genetic test in so far as it represents a biological measure that is associated with the later risk of a disease.
We defined an expert as an individual whose PubMed citations showed a consistent pattern of publication in either informed consent or amyloid imaging. We defined a consistent pattern as at least three years of publications with attention to lead or senior author status and the quality of the publications based on journal type and citations of the publication. Our target was to enroll 10 to 12 experts equally distributed between the two fields, following suggestions in the literature that an expert panel should include the minimally sufficient number of respondents and that a panel of 10 to 15 experts is adequate for relatively homogenous groups .
To identify experts in the field of amyloid imaging and AD biomarkers, we searched Medline for recent and relevant publications, performing searches for keywords: ‘amyloid imaging’, ‘Alzheimer Disease (subheading ‘ri (Radionuclide Imaging)’)’, and combinations of keywords ‘Alzheimer Disease’ AND ‘amyloid imaging’. All searches were limited to publications written in English from the year 2000 to 2012.
For the search to find experts on informed consent and genetic testing, we conducted Medline searches for recent and relevant publications, using keywords ‘Informed Consent’, ‘Genetic Testing’, and ‘Ethics’ and combinations of these keywords. All searches were limited to publications written in English from the year 2000 to 2012.
We reviewed the search results and identified potential expert participants based on the criteria described above. We produced an initial list of 20 individuals with consistent publication records in amyloid imaging and 20 individuals with consistent publication records in informed consent. We then randomly arranged the list of experts and serially recruited them in batches until we achieved our desired numbers.
We solicited expert participation via email that described the three rounds of Delphi review and then sent letters to those who did not respond or for whom email addresses were not available. Follow up letters were sent two weeks after the initial solicitation. After three attempted contacts, it was assumed that an individual did not wish to participate.
Delphi round 1
All experts who agreed to participate were sent a PowerPoint slide set describing the basics of amyloid imaging and its role in trials such as the A4 Study. Experts then participated in one-on-one semi-structured telephone interviews with a trained research assistant (copies of the slide set and interview script are available upon request). The research assistant confirmed at the beginning of the interview that the expert had reviewed the PowerPoint slides. If not, the interview was rescheduled. The interviewer answered any questions about the slides. Experts were then asked questions to elicit their ideas about the process and topics to be covered during three different phases of the A4 study: before consent, after consent but prior to amyloid imaging, and after amyloid imaging. The goal of this step was to identify potential disclosure topics and an outline of the disclosure process. We transcribed interviews and reviewed responses to identify and remove duplicate responses, and standardize language. We organized responses into the following domains: topics, methods/steps, assessments, and materials for education and assessment. Each domain was again separated into three phases: before consent, after consent and after imaging.
Delphi round 2
We sent the revised response list to experts via an online survey. For each item, experts used a three point scale (should be included, unsure, should not be included) to rate the necessity/appropriateness of including it. We also provided space for experts to comment on the reasons for their ratings.
We compiled the responses and categorized items into three levels of support: consensus to include (≥80% support), mixed support (79% to 50% support) and not supported (<50% support). Mixed support items were construed as having been supported if the majority of remaining votes were ‘unsure’ rather than ‘do not include’.
We used the list of items with consensus support to draft text for an Amyloid Imaging Disclosure Process Instructional Manual (hereafter called ‘the instructional manual’) and to create an Amyloid Imaging Disclosure Process brochure (hereafter called ‘the brochure’). The instructional manual is intended for investigators and clinicians, and describes each topic and creates a template for the process of amyloid result disclosure in the context of the A4 Study. The brochure describes amyloid imaging and is intended for education of a person who is considering whether to undergo it in the context of a clinical trial. We subsequently revised and refined the text in both drafts in collaboration with A4 investigators.
Delphi round 3
We sent the draft brochure text to experts via an online survey. Experts rated each section (and the overall document) for clarity on a 1 to 5 scale (‘not at all clear’ to ‘extremely clear’). We provided space for experts to comment on the reasons for their ratings or provide suggestions for additional topics, changes and deletions. We used expert comments to revise the brochure, with particular attention to any sections with mean clarity ratings less than 4.
Examine readability with cognitively normal older adults
Based on the results of Round 3, we tested a template version of the brochure that was not specific to the A4 study with a group of five cognitively normal older adults. Participants were a convenience sample recruited from the University of Pennsylvania Alzheimer’s Disease Center’s normal control cohort, who had given permission to be contacted for studies such as this one. We selected these persons because they would be the kind of person recruited for an AD secondary prevention trial. We asked participants to review the brochure prior to a face-to-face meeting with a trained research assistant. The research assistant assessed understanding using standardized measures developed in the decisional capacity literature that asked persons to ‘say back’ the meaning of a section, and reviewed sections with poor understanding for suggestions on improving clarity.
Human subjects’ protections
The Delphi study did not require Institutional Review Board (IRB) approval because it was a project designed to develop educational materials and, thus, did not fall under the category of activities requiring review under the Common Rule. The interview with the cognitively normal older adults was approved by the University of Pennsylvania IRB and all participants gave informed consent to participate.