SUPPLEMENTARY MATERIALS

Table S1: Summary of study assessments

Instrument Description Administration

Health Literacy

- Rapid Estimate of Adult Literacy in Medicine (REALM)

Medical-word recognition and pronunciation test comprising 11 medical terms, arranged in order of complexity by the number of syllables and pronunciation difficulty; scores assign health literacy skills into 4 categories of grade-equivalent reading level

Study coordinator, 2 minutes

- Newest Vital Sign (NVS)

Measures health literacy level using 1 scenario of an ice cream container nutrition label; 1 score (6 items) includes assessment of two main constructs, numeracy, and reading comprehension

Study coordinator, 3 minutes

Comprehension

- Quality of Informed Consent (QuIC)

Measures subjects actual (objective - part A, 16 items) and perceived (subjective - part B, 14 items) understanding of cancer clinical trials to address 13 independent domains of informed consent; responses measured in a 3-item (part A) or 5-item (part B) Likert scale

Self-administered, 7 minutes

- Modified Deaconess Informed Consent Comprehension Test (DICCT)

Semi-structured interviews assess subjects’ understanding of 8 core elements of disclosure for the study they have agreed to participate in. Scores of 2, 1, or 0 are assigned to responses that indicate complete, partial, or no understanding of each element.

Study coordinator, 5 minutes

Anxiety

- State Trait Anxiety Inventory (STAI)

Measures anxiety and distinguishes it from depressive syndromes; 40 items to assess state/trait anxiety; responses rated on a 4-point Likert scale

Self-administered, 5 minutes

Satisfaction

- Study-specific and QuIC Supplement

Short study-specific questionnaire and selected questions from the QuIC supplement questionnaire will query patients about their overall satisfaction with the consent process, helpfulness of information provided, and comprehension of key study-specific elements of treatment

Self-administered,

5 minutes

Information location

- Study-specific Patients will be asked to identify 5 items of information within the consent document; time taken to locate items will be measured

Study coordinator, 5 minutes

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Table S2: Representative quotes to support themes identified on evaluation study around barriers and facilitators to implementation of ETRIC form

Interview Responses: Willingness to Utilize and Acceptability of ETRIC Form (Theme I)

Comfort with easy-to-read format

Principal Investigator “I would feel comfortable handing this to somebody. I think it would be easier…it’s less overwhelming to a person, I think.”

“I can envision just going through it with a patient even with little degree of familiarity, but being able to articulate the concepts much better than it would be if they were all condensed together.”

Research Staff “Absolutely. I think this format [two-column] is actually better for the patient.”

IRB Chairs/Staff “I think I would be [comfortable using it], just because I think it is easier to read.”

Factors influencing ETRIC use

Principal Investigator “If it’s just a matter of a line here or there that can easily be incorporated into this, it shouldn’t be too challenging [to use]. It’s not going to change the format of this consent, if it’s just to update some specific language.”

Research Staff "Our IRB loves figures, like the treatment schema. If you can break it down into a calendar, into some sort of diagram, they love it, because I think it does make it easier [to understand], and it does break up the consent."

“[It’s] good for the patient to know that they can withdraw at any time, and they can see that at the beginning [of the form].”

IRB Chairs/Staff “Our IRB really loved it, especially our community members. We rely on our community members to help us enhance patient understanding because [they] are not involved in research in any way, and we feel their comments help us to make sure that these consent forms are in language that someone would be able to understand.”

Legal/Regulatory “When it [ETRIC template] went to the board here, they [IRB] were very uncomfortable with allowing an outside template to come in for one study.”

Interview Responses: Perceived Value of the ETRIC Template (Theme II)

Helpfulness to patients

Principal Investigator “It looks like something that I would see maybe in a magazine or a newspaper. It looks easier to read. So I think that in that regard I’m more apt to read it because it doesn’t look overwhelming. I like that things are sectioned out easily; that you’ve got the lines actually in between them. It doesn’t read as one block of text. You’ve got nice tables in there that

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make it a lot easier to read. That to me, even though this document is numbered with 21 pages, that to me… it’s a lot easier for me to even get up the desire to read this because it doesn’t look too challenging.”

“One thing that’s very good is that people are maybe focused on different aspects or different sections and it allows you to go back and forth and find your place a lot easier when the sections are clearly separated from each other.”

“Briefly what I’ve read seems to be written at a very appropriate level for someone who’s not familiar with this terminology.”

“I think that it looks less intimidating for people. I mean even for me and I’m educated and have been doing this for years, but it’s much less intimidating.”

Research Staff “It doesn’t look like a wordy research paper that has tons of script. It’s just almost more of a periodical or newspaper that people would be more accustomed to seeing versus this huge legal-looking document that might be frightening.”

“This looks like it is larger and you have frequent bold headings; you don’t just have one heading – huge paragraph, and then one heading – huge paragraph. So it’s real easy to find things that you’re looking for.”

“This first page is not so overwhelming; even though it might look a little bit longer in length, it doesn’t look so overwhelming, where more patients might be willing to read it.”

“It definitely already looks easier to understand, I think, for patients, for me even.”

IRB Chairs/Staff “I do like the two-column approach, and we’ve read a number of papers that suggest that there’s a higher level of comprehension with the two columns rather than one.”

“The risks section where you clearly bullet pointed and delineated according to level of risk. We’ve seen this before, I think from your group, but it’s particularly useful.”

Legal/Regulatory “I like that you have highlighted and bolded the pieces that you want somebody to look at first on the page and the white space is really good.”

“You can kind of breeze [through] it quicker, if that’s a good terminology. I feel like I can quickly spot check it and get some big highlights.”

Helpfulness to health professionals and IRB

Principal Investigator “These types of simplified things that can jump out at a patient make it much easier for a physician when they go through the consent, physician or research associate or whoever’s doing it, when they go through the consent just to say, ‘okay, here are the key things that you need to know.’”

Research Staff “The background, the introduction, the purpose, it’s more defined…each section. Especially when you explain the blood samples for research;

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randomization; reinfusion of cells. It’s sometimes difficult for the patients to understand the randomization, how the infusion of cells goes, the evaluations and what happens. That is broken down very easily here to help explain to a patient.”

“This makes it a lot easier [to explain to the patient] because you might forget what you need to talk about next and you can just glance down and see a header and you know right away where you need to go, whereas if you have a lot of words, it is easier to get lost or forget what you are saying. It tells you exactly what this whole section is all about, so I like it myself.”

IRB Chairs/Staff “I’m looking at your risks section, and you do have the tables, which is awesome. I like that you have certain sections, like the section called risks and toxicities related to transplant, and you’ve numbered them and bolded the risk before you talked about it. So if I’m just skimming through I can go, ‘Oh, graft failure… graft versus host disease…’ That’s helpful for me, and potentially for oncology patients as well.”

“Overall it is well received at our institution…by our IRB.”Legal/Regulatory “What I like: A. Shorter; B. I like the bold print, and I actually like the

columns.”Met institutional standards for research consent

Principal Investigator “I think this is pretty good. It covers most everything you need to cover, all the required stuff.”

Research Staff “I think that it definitely meets our consents that are current and goes above that, so I wouldn’t think that would be an issue whatsoever.”

IRB Chairs/Staff “The things that we absolutely require are our contact paragraph and explanation of the [hospital] IRB and the statement of non-waiver, which is saying that you don’t give up any of your legal rights. That type of language is typically in consent forms anyway, we just have a specific way we like it worded, but even that, if it has the same meaning, I think the IRB would accept it.”

“I wouldn’t say there is a disadvantage to presenting it this way that I can think of.”

Legal/Regulatory “You have the pieces that we consider our boilerplate language. It looks very much like ours, just in a different format. Our HIPAA language is kind of incorporated into our standard consent… a lot of people try and give us a sheet like this.”

Interview Responses: Perceived Barriers to Implementation of the ETRIC Template (Theme III)

Factors detracting from center use

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Principal Investigator “What happens if this consent is considered more valuable comparatively and our consent, in [her] word, ‘tanks’, and the ETRIC does really well? Does that mean that we then have to turn around and change all of our consent forms everywhere in the institution? If that were the case, I think you’d have to make a very strong case for it because it would be an awful lot of transition.”

“If the local IRB says, ‘You should say this…’ As long as we have some wiggle room [in the ETRIC template] then I think it will be fine. When you’re going through the channels with the IRB, you have to be able to work with [preferred language].”

“The HIPAA [section] to me is kind of the least interesting part of the consent and hopefully the thing that people would have the least issue with, so I might be more inclined to put that at the very end.”

Research Staff “It’s still very, very long and I always question how much patients are going to read if they’re given something so big. It just happens to be the nature of the beast, like you can’t necessarily cut any of the pieces out. When you look at it and you print it and it’s like 32 pages, they’re like, ‘I don’t want to read that.’ Because it’s not the only consent they’re getting.”

IRB Chairs/Staff “I’m afraid our lawyers will never let us get rid of this one [current template].”

“We have contraceptive language that’s on our website that we generally prefer to use. We actually list contraceptive methods that are acceptable and not acceptable just to provide clarification to the subjects. We are willing to work with sponsors on contraceptive language.”

Missing elements for patients’ use

Principal Investigator “I feel like a lot of people have a graphic, whether it’s a chart or whether it’s a person with an IV getting stem cells in their arm. I find that it’s often very useful for patients in terms of conceptualizing the process.”

“It’s still too long, but I don’t know that we can solve that problem.”Research Staff “The only thing that I’m noticing is that it’s very long and I feel like

sometimes the length of things can lose people’s interest, but I think that is kind of unavoidable because we want to make sure that they really do understand the risks involved and the benefit of the research.”

IRB Chairs/Staff “The title of the study itself: A multi-center, Phase 3, randomized trial of reduced intensity conditioning and transplantation… I don’t know what HLA means and haploidentical.”

“The flow might keep going a little bit nicer if there’s brackets instead of parentheses and, if you have this online, have ‘see before you start your treatment’ as a hyperlink. I’m not going to bother looking if I can’t get to it quickly.”

Legal/Regulatory “Reinfusion of stem cells… so even reinfusion… they don’t know what

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stem cells are so they’re focusing on what a stem cell is, never mind reinfusion, so I would even take it a step more basic because it’s pretty overwhelming.”

“I think it’s more intuitive that you go through it and sign as you’re talking about it instead of expecting people to sign everything on the last page. They [IRB] want you to have all the signature pages on the back so they’re easy to find for them. I’m not so sure how useful that is for the patient to remember all those pieces they’re signing off on.”

Missing elements for health professional and IRB use

Principal Investigator “Another thing we’ve noticed is when you bury signatures in the middle of a document it’s extremely difficult to know where to look because they’re in different places in every document.”

“I think there’s a lot of people around here who think that length is a big issue and they would like to go to shorter consents, but I’m not sure they think that how the information is presented is a major issue.”

Research Staff “I don’t love the duplication of information. For me, I don’t read this way, so it’s harder for me.”

“It would be me just getting used to the column format versus the paragraph format.”

“Making some reference [to the fact] that there will be some difference between what we’re going to do for the study versus what we’re going to do for standard of care in the study purpose, because I think that might make a difference.”

IRB Chairs/Staff “When we say, ‘see this’ it [should be] in brackets because it means go somewhere else if you want more information; whereas parenthetical is giving you another name [for something].”

“Ending your participation sounds a little ominous for a transplant recipient. That might be personal, but you know they’re already nervous enough.”

Fails to meet some institutional standards

Principal Investigator “The IRB wants it in our format, so we will basically take these sections and move them into our respective sections in our format and modify it a little bit so that it flows better. That’s what we’ve been doing for CTN trials. We can’t just submit this as the consent form because it’s not in our IRB format.”

Research Staff “Now we write the times for when the patient are consented.” “One thing that is very time consuming for us to do, and a lot of times

they want it, is if there is a really complicated evaluation schedule, like for instance here, labeled 1-7, they want to see tables or visuals of that, so we have to make flow charts or something where the patient could [say], ‘I start here and then I go to this treatment, and this treatment goes to this treatment.’”

“They [IRB] would definitely push back on the two-columns. They would

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push back on all the different bullet points, some of the drugs, and things being bolded because it makes it seem as though one thing is more important to read than another. They usually try to stay away from bolding certain sections of things unless it was a subheading just because patients’ eyes will tend to draw to that and think, ‘This is probably important because it’s bolded.’”

“Our IRB office really wants us to emphasize the research piece of things, rather than ‘what are all the evaluations required by the study or the standard of care.’ They don’t really want us to be including that [standard of care] in the consents.”

IRB Chairs/Staff “We would only have minor elements that I can see would be a problem here. I actually like the risks sections very much. We do not normally ‘invite’ subjects; we ask them to ‘consider participation.’ We generally consider “invite” as having some subtle coercion to it. It makes people feel some pressure to accept.”

“Institutions do reimbursement for injury differently. Because of the difference between institutions it’s really hard to craft any general language that’s going to make all general counsels happy and that’s going to suit all situations of a university.”

Legal/Regulatory “The only other piece I can think of is the World IRB [Western IRB], and if you had that, all other IRBs would kind of follow WIRB. It’s the only federal [IRB] we’ve got. If you had it agreed to by them for all of your sites, I think you might have an easier time.”

Interview Responses: Previous Experience with Alternative Consent Forms (Theme IV)

How patients and families review consents

Principal Investigator “I think every patient is different, and there are some patients who really want to look through it in detail, are very involved in their clinical decision making, and there are other patients who are very removed from their clinical decision making and will say to me, ‘Well, Doc, you know, I trust you. You’ve been taking care of me for a long time. I’ll do what you think is best.’ Then there are other patients who, you know, we’ll go through it [together]. We attempt to make every effort to give patients ample opportunity to read the consent in detail before they sign the consent.”

“At least one-third of the patients don’t look at it at all except to see, ‘Where is the line that I sign?’. They are strictly relying on the verbal communication, even if they are encouraged to read, which I think we do… It seems to me that roughly another one-third of patients take a cursory look at it. They don’t take it home; they don’t mark it up. Just from observations it’s hard for me to believe that they read every line. Maybe one-third of patients, perhaps it is less than that, really have clearly

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read it, have taken notes, come back with specific questions relative to language in the informed consent.”

Research Staff “It definitely depends on the study. I think if it has something to do with their treatment then that is something that they usually take home so they can go over it with their family and highlight; ask any questions when they come back so that we can answer those questions. If it’s for a trial that’s a just a database, or if it’s just blood collection or things like that, they typically like to just glance through things and are able to sign it there on the spot.”

“More often than not, I have them bring them it back, either a day later, or later on that afternoon after they’ve had a chance to read through it if they want to. Most patients don’t care. They just will sign anything that you put in front of them, which is concerning to me.”

“We have a lot of elderly patients and they might take it home to their children, and then their children have to ask questions but then their children can’t come back to the hospital with them for their appointment. So their children might kind of say, ‘Make sure you ask that question,’ and they forget about it. Where I think the whole purpose is for it to be easier to read for themselves.”

IRB Chairs/Staff “A lot of people don’t read the consents, they sort of say, ‘You tell me doc. You tell me what it’s about. I trust you. What do you think I should do?’… This is a full disclosure country; you have to know what these things are or else we haven’t done the kinds of things we have to do, to do this study.”

Legal/Regulatory “If it’s very complex, like the CTN studies typically are, they use it to refer back and to say, ‘Okay, what did I agree to do? What is my schedule? How frequently do I have to come to clinic? What are they going to do to me?’ Those kinds of questions for sure are what this becomes a reference guide for. And, as I’m sure you’ve heard from other people, sometimes people don’t want to see it. If it is an emotional decision and it impacts a lot of people in their life, sometimes they don’t want to look at it too deeply.”

“It depends on the education of the patient, frankly. I think you have the lawyer or engineer that really wants to look. They focus on different parts of the consent depending on what their background is, so somebody with maybe some biology background might be looking at the quantity of blood that’s drawn or how much marrow, somebody from financial aspect might be looking at, ‘What is my reimbursement?’”

Awareness and use of ETRIC format

Principal Investigator “It’s not the style that we use for our internal studies, but I’m familiar with it... I also reviewed your article published in BBMT and all that other stuff, so I’m very familiar with it.”

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“I can’t say that I’ve seen that before.”Research Staff “No [haven’t seen it]. I think we use our format and this [ETRIC

template] is translated into ours because we have a standard one with topics that the consent has to cover and standard language.”

IRB Chairs/Staff “I’ve seen things like this. I reviewed it for the IRB review.” “First time I’ve seen it.”

Legal/Regulatory “I’ve seen it before. I used to work at [hospital name] and they had a consent form that looked very similar. Same kind of layout more or less, with the two-column thing, and the way it separated out… honestly I don’t remember if the blocks were in the same order, but it looked similar to that.”

Other consent formats

Principal Investigator “Prior to this I would say that I’ve never seen what I would consider to be a very novel informed consent. I would say I have seen some significant variation in the quality of them, and by quality I mean whether someone has made a successful attempt or not to let’s say get it at an eighth grade reading level. Some informed consents, clearly an effort has been made to do that, and I think there is a way to not miss the salient points but also to make it very understandable.”

“I have rarely, if ever, seen an informed consent with a picture or a graphic. It’s almost, virtually it’s always paragraphs and pages of text.”

Research Staff “This has been the largest change in consent format that I have had to deal with since I’ve been doing this.”

“[I have seen] one single paragraph with bullet points and things of that nature.”

IRB Chairs/Staff “Typically the format we see is not the two columns and I would say they vary quite a bit in terms of the study, in terms of length. I’ve seen thirty something pages, but that’s a very complicated blood and marrow transplant protocol versus maybe a shorter informed consent for…or even a short form for interview types of studies.”

Legal/Regulatory “They actually had one [consent] on a computer and it was interactive and was made for children who may be able to read, but might not be able to understand all concepts. It was done almost like a game, so as you ran through it, it told them what to expect. It was for children with sickle cell disease and thalassemia, what their disease was, and it had a goofy little cartoon about the cells and what we’re going to do those cells, why we were collecting them, and then lastly, what was expected from them. Their parents would watch it as well, and usually you would discuss it afterwards.”

Interview Responses: Educational Resources for Clinical Trials (Theme V)

Helpful resources for patients or IRB members

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Principal Investigator "I think that pamphlets are helpful… The other benefit of the pamphlet is it allows us to provide them information before they actually arrive here. ‘This is a protocol we’re considering for you,’ and they have more time to think about it and to do their own research if they would like.”

“What would be good would be a short form and a long form. Or like when you buy like a new piece of electronics they’ve got the quick start manual and they have the in-depth guide.”

“Glossary of terms would potentially help, but where’s it located? You have to hand it to them separately because just in the back, then it’s not going to be helpful.”

“A visual aid, so it’s not entirely dependent on the text, would be useful.” “You can make a strong case that for multi-center trials there has to be a

single consent form across all institutions. The only way to achieve that is to have a single IRB that has the protection of the federal government and take responsibility for consent forms. Therefore, each participating institution is not liable for any perceptions of injury or whatever as a result of misinformation on the consent form. But if you have an institutional trial then the institution should be able to dictate how its consent form should look.”

Research Staff “I could see the merit of having some sort of a cover sheet that says very clearly, and in as few words as possible that, ‘You must sign page 8 and page 12’… something like that.”

“If there is a really complicated evaluation schedule, like for instance here - labeled 1-7, they want to see tables or visuals of that. So we have to make flow charts or something where the patient could go through and be like, ‘Oh, so I start here and then I go to this treatment, and this treatment goes to this treatment.’”

IRB Chairs/Staff “Hyperlinks on the electronic version of the consent when you’re cross-referencing other sections.”

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Supplement Figure S1: Example of easy-to-read consent form in two-column format

From Denzen EM, Santibanez ME, Moore HE, et al. Easy-to-read informed consent for hematopoietic cell transplantation clinical trials. Biol Blood Marrow Transplant 2012;18:183-9.

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