We analyzed twenty FIH study consents for six cancer types (14 for each solid tumor, 2 for hematologic malignancies, 1 B-cell lymphoma, 1 multiple myeloma, 1 gastrointestinal, and 1 lung cancer) and analyzed five consents for the Window trial in four cancer types (1 lung cancer, 1 gastrointestinal cancer, 1 head and neck cancer, and 2 breast cancer). 34 (17 for each trial type) of 42 (81%) patients approached participated. Four Windows patients and 2 FIH patients refused, and another two Windows patients were considered ineligible because they had not reviewed the Window study consent form. The 17 Window participants participated in four different trials (5 in a lung cancer trial, 4 in a gastrointestinal trial, 7 in a head and neck trial, and 1 in a breast cancer trial). The 17 participants in the FIH trial participated in 10 different trials (13 in solid tumor trials, 2 in lung trials, 1 in myeloma trials, and 1 in B-cell lymphoma trials). Theme saturation was achieved with 17 participants.
Ten of 17 (59%) participants in the FIH trial realized they were in the FIH trial. Six of 17 (35%) participants in the FIH study expressed concern about the consent in general (3 wanted the consent to state more clearly that the drug was researched, 4 found it confusing and disorganized, and one said it was boring). Six of 17 (35%) participants in the Window study expressed concern about consent in general (2 wanted a more detailed explanation of the study groups, 2 found the time frame for the trial confusing, 5 found the language of the consent confusing and wanted it to be used lay terminology and one stated that the consent should be shorter with fewer added legal elements). Participants can mention more than one problem. When asked what should be included in an ideal consent, the standard elements of consent were mentioned, except that 4 of 17 (24%) FIH participants wanted the specific benefit of this drug to be stated instead of the standard statement that the investigator could or it may not be of any use to you. Three of 17 (18%) FIH participants wanted the time commitment of the trial to be stated in a simple sentence in addition to multiple paragraphs describing the time frame of the procedures. And 4 of the 17 (24%) participants in the Window wanted the specific costs for them to be indicated, which unfortunately would not be possible.
Results of a first human trial
Patient preferences versus consent form placement for FIH trials are listed in Table 1. One consent form (5%) did not mention FIH information anywhere. Fifteen participants (88%) stated that they believed FIH information should be “one of the first things”/”front”/first few pages. Eighteen (90%) of the consent forms listed side effects found in animal studies conducted prior to the trials. Five (25%) mentioned animal data/non-clinical data more than once. Our focus on FIH information is supported by the qualitative responses to the question of what should be included in the consent form with 8 of 13 (62%) comments identifying information about the drug, its risks and benefits. Clarifying that the drug has never been used in humans before is key information about the drug and that the risks and benefits are extrapolated from animal studies.
Fourteen (82%) FIH participants felt it was important to include preliminary data from animal/nonclinical trials in consent forms, and 10 (58%) participants wanted to know side effects identified during animal/nonclinical trials. Twelve out of 17 (71%) of participants felt that side effects found in animal studies should go in the risks section rather than earlier in the document. Two (10%) of the 20 FIH consent forms mentioned animal data in the purpose, 7 (35%) in the study drug determination and dosing section, 9 (45%) in the risks section, and 2 (10%) ) did without mentioning animal data.
To summarize, participants preferred that FIH information be included in the purpose of consent form and in the risks section. Data from animal/non-clinical studies must be included in the consent form, but the specific location of this information may vary. Possible side effects of the study drug should be included in the risks section.
Based on patient interviews, we propose a FIH consent form template (see Additional file 1 ), including patient-preferred locations for FIH information and animal/non-clinical data. We used the Winship Cancer Center IRB-required consent template as the basis for our template .
Patient preferences versus placement of the Window trial consent form are listed in Table 2. Five Window trial informed consent forms were used during 2019–2022 at Winship Cancer Center. All five consent forms included the information that there is no guarantee that the patient will benefit from the study in the benefits section.
Patient preferences for the location of the risk of delaying surgery (delay information) varied (Table 2). However, it should be noted that while 41% (7/17) of participants felt that delay information should be located in the risk section, 53% (9/17) wanted the information listed earlier in the consent. For those trial participants whose consent was delayed information at the end of the risks section, 7/11 (64%) wanted the information to be stated earlier. Our focus on delay information is supported by the qualitative responses to the question of what should be included in the consent form, with 9 of 28 (32%) comments identifying the risks of the trial and 3 (11%) comments specifically mentioning potential delays in the operation must be explicitly stated in the consent. Another 6 (21%) of the comments mentioned that the time frame of the process should be included.
Participants made additional suggestions for the placement of various elements in the consent form and regarding. Fourteen out of 17 (82%) felt that the term “study drug” should be explained in the introduction or purpose of the consent form. Fourteen (82%) agreed with the NCI consent template that the study schedule should come before the risks section. Twelve (71%) of the participants wanted the trial schedule to be presented in a diagram/point format. Whenever possible, the informed consent form should include a one-page summary or page of key concepts of unique risks and a graphic, as 11 (79%) of participants said this would be helpful. Three of the 5 (60%) Window concordances explained the target as “investigational drug”. All five consents followed the NCI template, putting trial schedule before risks. Four of five (80%) consents noted the trial schedule as preferred by patients, and only two (40%) of five had a key concepts page.
Based on patient interviews, we propose a consent template for a window trial (see Additional file 2 ), including patient-preferred locations for delay information and study drug explanation. We used the Winship Cancer Institute IRB-required consent form template as the basis for our template .