‘Sick and tired’: Patients reported reasons for not participating in clinical psychiatric research

Abstract Background Meaningful and generalizable research depends on patients' willingness to participate. Studies often fail to reach satisfactory representativeness. Objective This paper aims to investigate reasons for not participating in research among young adult patients with psychiatric illness. Method A quantitative cross‐sectional study was performed based on questionnaires reported on by 51 psychiatric patients (14 males, 35 females and two unspecified) who had previously declined participation in an ongoing research project. Thereafter, a qualitative interview with subsequent content analysis was conducted with ten additional patients (five males, five females). Results The questionnaires indicate being ‘too tired/too sick to participate’ as the most common barrier. Lack of time and fear of needles were other common barriers. Lack of trust or belief in the value of research was less inhibitive. In the interviews, disabling psychiatric symptoms were confirmed as the main reason for not participating. Several potential ways to increase participation were identified, such as simplification of procedures and information as well as providing rewards and feedback, and building relationships before asking. Conclusion This study is unusual as it focuses on the group of young people attending psychiatry outpatient clinics we know very little about – those who do not partake in research. Our results indicate that fatigue and sickness reduce research participation and identify factors that may facilitate enrolment of this important group.


| INTRODUC TI ON
Patients' willingness to participate in clinical research is crucial for producing meaningful and generalizable results. 1,2 Today, many studies fail to reach representativeness, 3,4 regardless of study design, country or field of research. 5,6 For example, a review found that only a third of the original target population were recruited in randomized, controlled multicenter studies performed in the UK between 1994 and 2002. 7 In addition to the risk of misleading outcomes, 8 scientists are also often forced to cancel research in advance due to an insufficient number of participants. 6 Participant recruitment in psychiatric research is particularly unsatisfying. 9,10 For example, only five to ten percentage of patients screened for affective and schizophrenic disorders in large multicenter trials agreed to participate. 10 In order to tackle research recruitment problems, knowledge of what influences study participation is needed. Regarding research in general, the decision to participate is often based on altruistic or personal reasons. 11 Age has an impact: elderly people tend to decline to participate more frequently, possibly due to the recruitment process and study design not being optimized for senior participants with regard to potential vision, hearing and physical disabilities. 8,12 Ethnicity, sociodemographic and socioeconomic factors have been proposed to have an impact, but data are inconclusive. [13][14][15][16] Expectations of better treatment and concerns about health in general as well as extensive disease duration prior to the request, and experiences with ineffective treatments also increase research enrolment. 17 Conversely, hesitations are often based on concerns about injury or practical inconvenience such as time expenditure, 18 and these reservations seem to have a greater impact than motivating factors. In regard to biobanks, attitudes are predominantly positive. Participants often feel that their contribution is important and will benefit both themselves and others. [19][20][21] Concerns about insufficient data protection 22 and invasive sampling methods affect participation negatively. 23 Information concerning study outcomes is appreciated. 24 In clinical psychiatric studies, patients suffering from mental illness also report a positive attitude towards research. [25][26][27] Expectations of obtaining more consistent follow-up and being a 'special patient' rather than just a name in the system have been described as motivating factors. 28 Similar to medical research in general, altruistic factors, 29 insight and trust in research, convenient demands of participation, 'biological benefits' and receiving some kind of reward also lead to positive attitudes towards participation. 16 Participants with mental illness also show great interest in being informed of the study results. 26 The opposites of the abovementioned factors, lack of trust, the burden of participation and lack of compensation or benefits reduce the willingness to take part. 16 The stigma entailed by psychiatric diseases may also affect research participation negatively. 2 Patients with mental illness are considered particularly vulnerable to ask about research participation, since psychiatric diseases may influence decision-making ability and the process of informed consent. 30,31 Some research methods might also contribute to increased stress (such as disclosure of personal information in a group context). 32 However, studies specifically asking those who declined to participate are few. 33,34 This study aims to investigate the reasons why young people attending psychiatry outpatient clinics decline to participate in clinical research, including biobanking, and to examine whether and how their rejection could have been changed. This knowledge may be used to facilitate patient participation, especially for those with most symptoms, and thereby increase representativeness in psychiatric research.

| Ethical permission
Since this study included psychiatric patients who had previously declined research, participation ethical issues were raised. Two dimensions of vulnerability, capacity and voluntariness, were considered. 35 Patients were invited when they already had an ongoing treatment and were clearly informed that this would not be influenced by their decision. The study received ethical permission from the regional ethics board in Uppsala (Reg. no. 2012/081 and Reg. no. 2016/412).

| Study design
This report contains a quantitative cross-sectional study based on questionnaires and a qualitative interview study with subsequent content analysis.

| Study sample
Uppsala Psychiatric Patient Sample (UPP) is an infrastructure for data collection and biobanking within the psychiatric clinic at Uppsala University hospital. 25 All new patients, aged 18-25, at the psychiatric unit for young adults are consecutively asked during their first visit at the clinic to participate in UPP by contributing data and biological samples (ie blood, saliva, etc). In 2015, when more than 1100 patients had been approached, 41.4% had chosen to take part.
In 2016, we wanted to approach the group who had denied participation, and UPP rejectors needed to be identified, but there was no register over non-participants for the current study. Therefore, recruitment occurred during an ordinary visit to the clinic. The patients were approached by their regular contact, who was instructed to ask the patient whether he/she had participated in UPP. Patients who reported that they had chosen not to participate in UPP were then asked whether they would consider contributing knowledge about why people choose not to participate in research, by responding to a questionnaire. The number of patients approached was not registered. Participants completed the questionnaire anonymously, set it in an envelope and dropped it in a locked mailbox. That was regarded as informed consent to participate in the quantitative study with preserved anonymity. Patients were recruited during the period of February to November 2016. In total, 51 patients, 35 (68.5%) women, 14 (27.5%) men and two (3.9%), who did not specify sex, completed the questionnaire. The time passed between declining participation in UPP and being asked about participating in this study was not recorded, but could vary from months to years.
In addition, a qualitative interview was performed with ten additional patients, five women and five men. After using the same recruitment procedure and information about the interview study had been given orally by their regular contact, interested participants were contacted by phone and given the opportunity to ask questions. Written consent was then collected for the interview study by the interviewer. The sample size was not adjusted based on analysis of saturation. Instead, ten individuals, all patients during the period of recruitment that choose to take part in the interview, were included.

| Questionnaires
The questionnaire was constructed as statements, based on the most commonly reported reasons to decline research participation. 18 Table 1). The questionnaire was not previously used in any research project, and no pilot was performed. Within this study group, the internal consistency was low, and Cronbach's alpha was .335.

| Qualitative interviews
A non-standardized, semi-structured interview guide was constructed for this study. The questions were drafted from six predetermined categories since the aim was to explore whether previous findings in research are present in this sample: reasons to not participate in research 8,37 ; reasons to participate in research 14,17 ; changeable barriers to research participation 9,36 ; general attitudes and thoughts towards research 28,29 ; attitudes and thoughts towards psychiatric research 25,26 ; and attitudes and thoughts towards biobanks. 21,24 The interviews were performed at the clinic by the first author (LB) who did not participate in the care of the patients. The dialogue was recorded, and afterwards, audio files were anonymized and transcribed into a total of 92 pages of text.

| Analysis of collected interview data
The transcripts were further analysed by content analysis, with a manifest and deductive approach. 38 The first author (LB), a medical student with previous internship in psychiatric care, carried out the analysis, and classification was then scrutinized, discussed and completed together with one of the other authors (CÖ), a researcher with long experience of qualitative analysis and extensive practice in the field of psychiatric care. Both authors read the transcripts several times. Units of meaning, identified from sentences or paragraphs and rigorously considered representative to the context, were extracted, condensed and sorted into codes. The codes were classified into one of the predetermined categories mentioned above. The categories were then divided into subcategories based on dissimilarities within the categories. The analysis continued until all subcategories were considered clearly defined and distinct from one another. 38

| Statistical analysis
For reliability analyses, internal consistency was measured by Cronbach's alpha and an inter-item correlation matrix was performed. Men and women were compared using the Mann-Whitney test. Data were analysed by the statistical program SPSS, version 24.
TA B L E 1 Consensus ratio for reasons not to participate in research among patients with psychiatric illness (n = 51)

| Quantitative cross-sectional study
The respondents' graded agreements in the questionnaires are presented in Table 1.
The most common reason to not take part in research was 'I am too sick/tired to participate'.
Men and women did not show any significant difference in de-

| Reasons to not participate in research
In the subcategory affected by disease, fatigue and energy loss constituted a major obstacle to research participation. Several respondents with symptoms of depression described that everything beyond the absolute vital tasks of daily life represented a big load.
Other disease-related reasons for not participating were social anxiety and planning difficulties in neuropsychiatric disorders.

| General attitudes and thoughts towards research
Most respondents expressed positive attitudes towards research and spontaneously reported that 'research is a good thing'. Science was also described as necessary, important and a contributing factor to better health care in society.
However, more negative thoughts also emerged, for example

| Attitudes and thoughts towards psychiatric research
The majority stipulated that research in psychiatry is a good thing and explained that this opinion was based on the fact that they could relate to it, and also benefit from it themselves.
Yeah, but… like I said, I'm in favor of this stuff. It makes me happy that this research is actually about something that concerns me personally. The participants also discussed the fact that mental illness might affect decision-making capacity. This can lead patients to accept tasks that they do not have the time or energy to accomplish.
Further, anxiety disorders and depressive symptoms were described as potentially affecting cognition, especially immediately after the first visit to the clinic, when they might have opened up and exposed their problems to someone they do not know for the first time.
The disease can make you feel 'lost in the world' and potentially 'weak and easily manipulated,' since you aren't in you right mind.
(Patient 9, female) However, all respondents answered 'no' when asked whether they consider the procedure unethical.

| Attitudes and thoughts towards biobanks
Several positive views about biobanking being a good thing were mentioned; it was described as an exciting field that leads to better medical care. Interestingly, the majority suspected that other people's attitude towards biobanking is negative, but stated that they personally approved.
If you have problems trusting people then maybe you don't trust that they will…, that they who have asked you to participate will do exactly as…they had said.   39 When understanding the sample bias introduced by this factor, it is important to emphasize that it is psychiatric symptomsrather than psychiatric disorders -that seem to constitute a barrier to research participation.

| D ISCUSS I ON
The ability of patients with a psychiatric illness to understand information and make decisions has frequently been discussed. 27,30,31 This study suggests that patients with a psychiatric illness consider these abilities to be affected themselves. There was however no indication, even when asked directly, that these patients considered inquiries about research participation uneth- ical. This provides valuable information; in recent years, research ethics have been frequently discussed, but patients' own opinions are rarely available. 29 The invitation to participate in research was experienced negatively. First, the timing of the request in conjunction with the patient's first visit was criticized, and second, being asked by an unknown person was criticized. Although previous studies have given little attention to this aspect, it has been mentioned that not knowing the scientist/recruiting clinician has a negative effect on willingness to participate. 37 Furthermore, trust in clinicians and particularly the patient's treating doctor plays an important role in the research recruitment process. 10 In UPP, the patients are asked by a research nurse and not by the clinician.
In the quantitative study, several respondents reported that they did not feel a lack of trust themselves -but thought that others probably did; for example, they raised a fear of their personal data and submitted biological samples being handled differently than what had been promised. These concerns have also been reported in previous studies. 22,40 Furthermore, suspicions were raised that research results can be manipulated to show what the research group wants to see. Differences in outcomes between questionnaires and interviews may have more than one explanation. In a questionnaire, pre-formulated statements cannot capture every possible thought and reflection among respondents. Another factor to consider is that the number of participants differed in questionnaires vs interviews. Furthermore, the questionnaires pertained to participation in UPP, whereas the interviews also discussed research participation in general.
The majority of the survey respondents were women, while the number of female and male respondents was equally distributed in the interviews. In research involving patients with mental disorders, however, women participate more often. 41,42 Gender bias is not reflected in participation in biobank studies in general. 43,44 However, the probability of participation in biobank research among patients with mental disorders is larger among women (in certain categories). 45 It may be speculated that men with psychiatric disorders lack trust in research to a greater extent and therefore choose to abstain more often, but this was not evident in our results and requires further research.
Another pattern that can be discerned from the interviews is that research participants would be encouraged by something in return for their participation, including not only material things, but also appreciation and confirmation. For example, letters with information about how the study is proceeding, if progress has been made, and a 'thank you' for taking part were proposed ideas. Participants in a previous study 24 also wished to be informed of the study results.
This type of reward may better indicate the value of their participation. This wish must be considered in relation to routines for data protection. If all data concerning participants' details is destroyed after collection, as it is in many studies, it will not be possible to contact the participants.
The purpose of this study was to investigate factors that prevented young patients with a psychiatric illness from participating in research. Although the study included a quantitative portion, literature on the field is inconclusive; therefore, the study aim was framed as descriptive rather than hypothesis-testing. Recruitment was rendered difficult by the fact that the target group (patients who rejected UPP) had already declined to participate in research.
No registers of 'UPP decliners' existed, complicating the delivery of questionnaires. Instead, the staff was instructed to ask all visitors whether they had accepted or rejected UPP. The patient who reported rejection could then choose to answer the questions or not, and no oversight of their participation status was conducted.
The reasons for declining participation in both UPP and this study thus remain uninvestigated. The study has several other limitations.
Ten respondents choose to take part, and all were included in the interview study. Data saturation could therefore not be used in the recruitment procedure. This is a limitation and may lower generaliz- which is an important finding as well as their suggestions for improvements, such as simplification of procedures and information, the timing of the request and greater personal rewards for patients.

ACK N OWLED G EM ENTS
The authors wish to sincerely thank all of the participating young adults.

CO N FLI C T O F I NTE R E S T
None of the authors have any conflict of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing is not applicable to this article as no new data were created or analysed in this study.