Participant perspective on the recall-by-genotype research approach: a mixed-method embedded study with participants of the CHRIS study

A total of 50 CHRIS participants invited to participate in the study agreed to participate (100% of the RbG study participants). A relative of one of the invitees asked to join and was included in the empirical study. One participant left the study center without participating in the interview. As a whole, 51 participants responded to the questionnaires, and 50 participated in the interview. Table 2 shows the socio-demographic characteristics.

We identified four main themes. They represent patterns of meaning concerning participant response to RbG invitation and participation. Participant response was thematized as follows:

1. (a)

   Information filter through personal experience: Participants filtered received information through personal experience. This occurred through reflecting on heredity and the reaction to receiving the invitation.

2. (b)

   Stress relief mechanisms: Participants enacted mechanisms to alleviate stress related to the invitation and participation in an RbG study. They consisted in resorting to personal resources and in seeking support from experts.

3. (c)

   Targeted information matters: Targeted information was important for participation. Participants decided based on the information received, and participant engagement depended on the information received.

4. (d)

   Expectations on disclosure: The expectation concept included what is desirable (or non-desirable) and acceptable (or non-acceptable) to know or not to know in an RbG study scenario. Participant preferences for disclosure of the disease under study and of the carrier status varied according to how the knowledge of individual carrier status was perceived to impact participant’s life (Table 3).

Information filter through personal experience

The qualitative data analysis showed that, while reasoning on their recruitment and interpreting the invitation, participants resorted to their own experience and concept of genetic disease transmission. They inferred risk and carrier status from the disease’s familial history and other family members’ invitations. For example, inviting more people from the same family made a few participants presume that the whole family was a carrier of the genetic variant or was affected by the disease:

“When I got the invitation, my mother got the invitation at the same time, and my two half-siblings didn’t. That made me think a bit at first, because I thought, okay, it could also be that I got this gene from my mother and from my biological father and, as my two siblings have a different father, didn’t get the gene, because they probably don’t carry it or don’t carry it in duplicate. That was my first train of thought. Then my mother’s sister and her son were also invited. So, I thought, maybe it’s something that really affects the whole family because four people from one family is quite a lot. I47”

The invitation made participants think about Parkinson’s disease and the risk of developing the disease. They reflected on their health, speculated on their carrier status, and the possibility of genetic transmission of the variant to future generations. In the questionnaire, more than half of the participants thought about the possibility of being carriers of the Parkin gene variant (Table 4, A1). Participants expressed different degrees of concern related to being a carrier of the variant and of the perceived likelihood of belonging to the control group (A2, A3). Participation in the RbG study caused an increase in worries and risk perception of developing Parkinson’s disease only in a small fraction of participants (A4, A5). Additionally, data showed that participants struggled with estimating the risk of developing the disease (A6: 41% chose I don’t know). 35% of participants reported a family history of Parkinson’s disease (A7).

Stress relief mechanisms

In the interviews, a few participants observed that the invitation raised concerns and often temporary worries. These were solved by resorting to personal resources and the experts’ support. Personal resources consisted in re-reading the letter several times and consulting family members. Support from experts consisted of face-to-face conversations with the medical doctors conducting the clinical examination and interactions with the study assistants, medical doctors, and researchers involved in the study. Participation at the study center was perceived as a positive and comfortable experience. Consulting the experts provided relief, reassurance, and an opportunity for further clarification:

“I had to read the form twice, because the first moment I saw it, my first thought was: do I have Parkinson’s disease or something? […] Then, you don’t read through very carefully […] you read it with fear and maybe you only read out what you are already afraid of. And then I gave it to my husband to read and he read it more thoroughly and then I read it again myself and then I really understood that it was actually, as the doctor explained it to me today. And the doctor’s explanation again today made it clear to me what it’s all about. […] it was very helpful to get rid of fear and also to know something about how this research works and proceeds. I16”

A trend in emotions before and after participation was found through the quantitative data analysis. By comparing the distribution of the scores assigned in the questionnaire to each emotion at the time of the invitation and after participating in the study, the number of participants reporting positive emotions (carefree, delighted, relieved) with high intensity increased after participation, while the number of participants reporting negative emotions (nervous, anxious, worried) with high intensity decreased after participation (Fig. 1). For the “curious” emotion, a specific pattern on the score assigned was not identified. Participants reported not feeling upset when receiving the invitation or after participating (except one). Additionally, none of the respondents regretted being invited to the study (50 did not prefer not to be invited, and one not answered).

A similar positively correlated trend was found in the satisfaction with the information received before and after the visit: before coming to the study center, only a minority of the participants had questions unanswered or unclear; after participation, almost all respondents found that most or all their questions were addressed and answered, and had their doubts adequately clarified and addressed (Table 4, A8, A9, A10). In the interviews, participants raised issues of clarity, complexity, exhaustivity, and amount of the material provided as elements that affected their understanding of the information received in the invitation.

Targeted information matters

Qualitative data showed that participants saw participation in the Parkin RbG study as a contribution to a meaningful cause with benefits for future generations and society. Personal interest in the clinical examinations and utility for own health were also reasons, shared by most participants, for participation:

“I can help research with it [through participation in the study, Ed], but it also helps me, because I really do get a health check-up for free. I23”

“I found it interesting that something is being researched. Because I want to contribute to the results and if you can help, then why not. […] I thought that this could also be of use to me. If something turns out or if there are interesting things in the future. I15”

Additionally, motivations for participation were contextualized in terms of engagement with the CHRIS study:

“If you get an invitation, then it’s somehow an obligation to go. I46”

Quantitative data showed that most participants would like to know the disease associated with the gene variant under study (Table 4, A11). The analysis of qualitative data showed that, while non-disclosing the disease under study would negatively affect the willingness to participate and engagement, the interest for the specific disease under investigation worked as a motivator for participation:

“I am a nurse and have therefore often had to deal with Parkinson’s patients in my life. My grandmother had Parkinson’s disease. And a very good friend of mine had a very early form of Parkinson’s when she was just over 40. And I personally would be happy to support any study on this subject, like many other studies, if I could. I35”

A few participants clarified that being informed on the area of investigation and the aim of the study was important, not only to be aware of what they were contributing to but also not to feel objectified and instrumentalized as research participants:

“From my point of view, it is important to inform participants, considering that they participate as volunteers, otherwise, someone will be treated as a guinea pig or something. Blood is taken and one doesn’t know where and for what, and I would be in favor of the information simply being available. I14”

On the other hand, for a few respondents, the decision on participation was not based on the disease under study and disease disclosure.

Expectations on disclosure

The survey showed that most participants were fine with genetic research results not being returned to them in either individual or aggregated form (Table 4, A12). Correspondingly, interview respondents deemed the practice of no return of genetic research results (either individual or aggregated results) acceptable. Participants expressed the view that genetic research results had no direct value for them and that they served for research purposes only:

“I am not interested in the findings for research purposes […] I am not a researcher. I49.”

Participants distinguished genetic research results from clinically relevant or actionable findings, which were expected to be returned, given their possible utility for their and their family’s health:

“For me, it is simply important that if I am really a risk patient, and that is clear from the results, that there is something coming up for me, and above all for my family, that I am perhaps informed. So, basically about genetic information, I can’t do anything with that. I13.”

Genetic research results were perceived to affect family also in a negative way:

“I think if I knew that I had some kind of genetic change that would lead to some kind of serious illness or something, then I would maybe decide not to have any more children […] Then I would be afraid. So, it would really be a drastic life change if you knew that. Then I would probably spend ages finding out whether I should have another child or not, or it would make me feel insecure. I18”

The quantitative data showed that respondents were split into two approximately equal groups as regards willingness to know their individual carrier status with respect to the Parkin variant under investigation (Table 4, A13). However, during the interviews, the majority of participants deemed the non-disclosure of the Parkin gene carrier status acceptable. Given that heterozygosity does not lead to the development of Parkinson’s disease, disclosing the carrier status was considered irrelevant, useless, and without diagnostic or predictive value for a few participants. A few participants not only found the non-disclosure acceptable but also did not want to know their carrier status because they perceived that such information would cause unnecessary burdens and concerns (e.g., being aware of one’s heterozygous condition may affect family planning). On the other hand, a few participants would have liked their carrier status to be disclosed: In this case, their motivation was curiosity or/and they found that such information contributed to their awareness about their health:

“I think I would worry, I don’t know, but I think I would listen to myself more purposefully or pay more attention to changes. […] I don’t think I would be more afraid, but I think that on the one hand, I would pay more attention and perhaps go to a doctor earlier, which could also be helpful. I23”

Quantitative data showed that almost all participants were willing to participate in further RbG studies (94.12% yes, 1.96% no, 3.92% not answered). Almost half of the participants evaluated not disclosing the disease under study in RbG studies negatively. In contrast, 17.65% in a positive way, and 31.37% found it partly positive and partly negative (Table 4, A14). For more than half of the participants, the type of disease would impact their decision about being willing to know the disease under study (A15).

During the interviews, participants were challenged with a hypothetical scenario in which an RbG study on a variant that increases the risk for a serious disease was conducted. They were explained that in such a case, they would have their carrier status disclosed and were asked to state their preference for being recontacted or not for participation and to explain their views. When provided scenarios, a variety of preferences were returned. Participants who wanted to know their carrier status saw its disclosure as a positive opportunity for prevention and actionability. This information was also seen to provide an awareness of susceptibility, which is essential for the development of responses and coping processes:

“I would like to know, you can prepare yourself somehow. You also have to protect the family somehow, so I would like to know. I13”

“If you have cancer or something, and there is perhaps the possibility that you can treat it at an early stage, it might be better to know at an early stage or what alternatives there might be. […] you can then deal with it a little or talk to people who are in the same situation and exchange ideas, on how are you doing in general, what are you limited in or what keeps you busy or do you somehow need more time for yourself, if you have to somehow cope with your fate now?. I29”

Actionability was used as a criterion for disclosure by those participants who wanted to be invited and to know their carrier status only if opportunities for prevention or therapy were available or in studies about non-causative variants:

“If there is a therapy, […] then I would like to know. If it’s something that you can’t do anything about at the moment anyway, then I personally would rather not know. I28”

A minority of participants did not want to know their individual carrier status nor wanted to be invited to participate in further studies on a pathogenic variant. They perceived that knowing the carrier status of a pathogenic variant was a burden:

“No, I don’t want to know. […] Because then it’s always in the back of my mind. I think that with every decision and with everything you have that in the back of your mind. I32”

Table 3 summarizes the above-described preferences.