Autistic adults’ views on the design and processes within randomised controlled trials: The APRiCoT study

Moral obligation

Interviewees conveyed a strong sense of motivation to participate driven by ‘duty’ and ‘striving to do the right thing’:

It was my duty to do it [participate in research], regardless of the topic. I feel obliged with a medical condition to try and improve research and help with research. (P33)

They recognised that being autistic, and the accompanying sense of duty and desire for fairness, may facilitate the participation decision. Consistently, about two-thirds of interviewees had participated in studies in the past:

Finding out information is quite an appealing sort of thing and altruism I think is part of the condition as well. And I think knowing that you would have the chance to do something that might help yourself, and also help everybody else, is a very appealing prospect. (P44)

Fair and honest process

Several interviewees found randomisation and blinding acceptable processes because they maintained fairness and honesty in terms of allocating treatment and achieving a valid study outcome, characteristics they valued highly. Furthermore, a few study participants emphasised how a double-blinded trial, where participants as well as researchers do not know what treatment participants have been allocated to ensure equality between the parties, dissolving power imbalances:

Randomisation is used to get a broad spectrum of people for a study so that it’s completely honest (. . .) I like the fact that the results will be true and can’t have been made up. Being autistic I like everything to be right and fair (. . .) I’d not mind not knowing because that’s the whole idea of complete fairness, so not knowing would mean that everyone taking part would be equal. (P11)

Introducing more uncertainty

Study participants felt that taking part in an RCT could introduce uncertainty in their everyday lives, which in turn could raise their anxiety. Most interviewees preferred to follow established daily routines that offered a sense of control in everyday life to minimise uncertainty. Participating in an RCT was perceived to not only require having to adjust to new routines, people and environments, it would also introduce key sources of uncertainty derived from the study design. Interviewees reflected on how they would react to randomisation, blinding, active medication and placebo in the context of an RCT of a medication for reducing anxiety (Rai et al., 2023), which was then in the set-up stage.

Being tricked into participation

Most interviewees expressed concerns about differences in capacity to provide informed consent among autistic people. We recorded a few strong opinions related to feeling tricked or deceived, that would dissuade someone from considering research participation in an RCT. Interviewees felt that autistic people may feel especially vulnerable because some find it difficult to tell when ‘people are being false or being true’ (P32), or because they may feel their right ‘to be able to make the decision for yourself without influence from parents, carers or others in your life’(P3) has been negated in the past. Interviewees highlighted that researchers have the responsibility of communicating effectively, providing accessible material and enabling autistic people ‘to feel motivated and [find out] how to get involved without using undue influence to participate like an army-enlistment-type campaign directed at autistic people, I think it is a very dangerous ethical grey area’ (P37).

Potential for rumination

A few interviewees thought if they were blinded to the treatment, they may spend excessive time thinking whether their reactions were due to the active medication, placebo or a more general deterioration in their condition – ‘The uncertainty of whether I was taking the placebo or taking the regular one would drive me crazy and wake me up at night’ (P38), exacerbating their reservations about medication trials.

Experiencing uncommon side effects

The potential of experiencing side effects concerned interviewees, who cited effects from their own experience such as excessive weight gain, changes in perception, fatigue and brain fog, as well as difficult withdrawal. Based on anecdotal accounts, many interviewees sustained the view that autistic individuals might react differently than neurotypical people to medication. They also observed that autistic people were more likely to be taking other medication for co-occurring conditions, which increases the chances of harmful medication interactions. This complex set of circumstances made participants feel more vulnerable and cautious about deciding to take part in an RCT:

I’ve read a lot of first-person accounts of people having different reactions to drugs and being sensitive to different kinds of foodstuffs. While that indicates that there is a need for additional research in this area, it’s not something . . . I feel very vulnerable about that. (P5)

A few people raised other specific medication concerns, for example, wanting to know if the medications contained animal derivatives.

Not receiving timely treatment

Despite understanding the reason for a placebo in an RCT, some participants felt they would be anxious or disappointed about the possibility that they might receive placebo instead of the active medication – ‘I think it would be a big waste of time. . . I would want the treatment group’ (P2). This stemmed from narratives of intense psychological suffering and a belief that an active intervention would be beneficial. This was expressed more so by those who had positive experiences of taking medication:

My chief concern as a participant would be that, if I were to enter a particular trial because I required its treatment or service, being randomised to the control group would mean I didn’t receive it. That problem would be exacerbated if I went to any expense to participate in the trial, or if it caused me any physical or psychological difficulty. I would worry about this if participating in an RCT. (P12)

Preferring alternatives to medication

A few interviewees considered the possibility of an active intervention being no better than placebo. The view that research into psychological interventions to support autistic adults’ mental health needs might be more preferable than medication interventions was also raised by some participants:

Giving someone medication is the much cheaper and more straightforward pattern, as opposed to giving someone more complex and more direct forms of intervention through psychology or specialist therapies. (P3)

Yet most accepted that those who are invited to participate in an RCT, have to ‘be relatively comfortable with the intervention it offered (. . .) and comfortable with not knowing whether or not I receive any particular one of the intervention (or control) options’ (P12).

Anticipating a placebo effect

Feelings about discovering they had been taking placebo at the end of the study varied from anticipating disconcert and confusion to happiness and surprise:

I can’t possibly imagine ever wanting to put myself in a situation where I might be thinking that I’m going to have side-effects, but I might be imagining them. (P5)

A few people recognised the potential for placebo to offer a positive learning experience, by providing an effective way to overcome anxiety. Other study participants were sceptical about autistic people experiencing a placebo effect due to their cognitive preference for facts – ‘everything is fact based (. . .) we don’t necessarily expect it to work’ (P7), while others thought there was a great capacity of the autistic brain to induce healing – ‘I do believe that the mind is powerful’ (P11).

Mind the language

Our interviewees discussed the ways in which the uncertainty involved in participating in an RCT might be minimised. At the top of their priorities was paying attention to the language used to explain the research, a key principle for accessibility to a research study. Interviewees felt study transparency as well as assurance that the research tools were appropriate and relevant for completion by autistic people would help promote trust in the research. For example, a participant noted how difficult it is to adequately express gender diversity in questionnaires:

I’d like to see a ‘which gender do you identify as? Women/Man/Non-binary/Other’ and ‘which sex were you born as? Female/Male/Intersex’ so that there’s more options especially in terms of healthcare for transgender people. It would be very helpful to know that information in a drug study like this (i.e., hormone effects and such). (P8)

Interviewees wanted transparent information about processes such as blinding from the beginning, assurance that intervention exposure was only temporary with rights to withdraw preserved, and that the study results would be relevant enough to have an impact in the whole community:

Knowing [what] ethical considerations are in place. What’s going to be done with the research – How’s it going to be used? How’s it going to make life better for people hopefully. (P42)

Detailed but easy-to-read information

Our participants explained that information about the study and treatments should include what RCT participation would involve practically, for example, where they would go and who they would see. Information needed to strike a balance between being sufficiently detailed but succinct and appealing to read – ‘make sure it’s not too in-depth and too wordy because I just wouldn’t read it’ (P26). To help alleviate anxieties related to inherent uncertainties of research processes, participants wanted information about defined lines of communication and clear protocols for adverse event reporting at the start of the study:

[Information] to almost be able to walk through an environment in my mind, to think about the different interactions that I might have and how I might respond to those. I’d have to plan that really carefully. (P5)

Precise language

Our study participants insisted researchers should strive to use clear and precise language, for example, a few people commented on an error in the description of ‘blinding’ emailed to participants prior to the interview (Supplemental material 2), which was in fact a description of ‘double-blinding’:

When I read your piece paper, at the end it said about blinding. And my immediate thought was, well, the actual line description was really more double blinding, rather than blinding. (P21)

Flexible access

Most interviewees emphasised that access to research should be flexible and consistent because ‘how easy it is to take part will be a facto’ (P36). They suggested taking advantage of online platforms to communicate, without discounting low-key in-person contact in a relaxing environment:

Doing a lot of things via email, that I think will help, limiting the face-to-face contact. Also, then, I think it’s more relaxed without time pressures. Certainly that’s something. . . I don’t respond too well under time pressure. (P1)

Committed to the study

Various interviewees described how despite anxiety produced by the trial design, if they were satisfied with the information received and reassurance from the trial team, they would put aside their anxieties and commit to the study. Although autistic people may take longer to decide whether to take part, they argued that once committed to the study, any ongoing anxieties would not interfere with their participation:

I would not like not being sure that I would see any benefit from the study, as would be the case if I were randomised to receive no treatment. However, I would not be worried about receiving the treatment without knowing – because I would already have made myself comfortable with the intervention options and I would trust the study team to follow me closely if there were any associated risks. (P12)