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Perceptions of risk and predictive testing held by the first-degree relatives of patients with rheumatoid arthritis in England, Austria and Germany: a qualitative study
  1. Rebecca J Stack1,2,
  2. Michaela Stoffer3,4,
  3. Mathias Englbrecht5,
  4. Erika Mosor3,
  5. Marie Falahee1,
  6. Gwenda Simons1,
  7. Josef Smolen3,
  8. Georg Schett5,
  9. Chris D Buckley1,2,
  10. Kanta Kumar6,
  11. Mats Hansson7,
  12. Axel Hueber5,
  13. Tanja Stamm3,
  14. Karim Raza1,8
  1. 1Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  2. 2Division of Psychology, Nottingham Trent University, Nottingham, UK
  3. 3Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
  4. 4University of Applied Sciences for Health Professionals, Upper Austria, Austria
  5. 5Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany
  6. 6Faculty of Medical and Human Sciences, School of Nursing, University of Manchester, Manchester, UK
  7. 7Centre for Research Ethics and Bioethics, Uppsala University, Uppsala, Sweden
  8. 8Department of Rheumatology, Sandwell & West Birmingham Hospitals NHS Trust, Birmingham, UK
  1. Correspondence to Dr Rebecca J Stack; rebecca.stack{at}ntu.ac.uk

Abstract

Objectives The family members of patients with rheumatoid arthritis (RA) are at increased risk of developing RA and are potential candidates for predictive testing. This study explored the perceptions of first-degree relatives of people with RA about being at risk of RA and engaging in predictive testing.

Methods 34 first-degree relatives (siblings and offspring) of patients with RA from the UK, Germany and Austria participated in semistructured interviews about their perceptions of RA risk and the prospect of predictive testing. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis.

Results First-degree relatives were aware of their susceptibility to RA, but were unsure of the extent of their risk. When considering their future risk, some relatives were concerned about the potential impact that RA would have on their lives. Relatives were concerned that knowing their actual risk would increase their anxiety and would affect decisions about their future. Also, relatives were concerned about the levels of uncertainty associated with predictive testing. Those in favour of knowing their future risk felt that they would need additional support to understand the risk information and cope with the emotional impact of this information.

Conclusions Identifying individuals at risk of RA may allow targeted interventions to reduce the risk and consequence of future disease; however, relatives have concerns about predictive testing and risk information. The development of strategies to quantify and communicate risk needs to take these views into account and incorporate approaches to mitigate concerns and minimise the psychological impact of risk information.

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Strengths and limitations of this study

  • This study used inductive qualitative interviews to explore perceptions about risk and predictive testing in the first-degree relatives of people with rheumatoid arthritis.

  • This study identified positive and negative perspectives surrounding predictive testing, and why some people at risk may not wish to be tested.

  • Further research is needed to quantify the numbers of people at risk holding negative perceptions about predictive testing and to identify the behavioural implications of these beliefs.

  • Communicating risk information to relatives effectively while reducing the psychological burden associated with this information should be the focus of future interventional research.

Introduction

Rheumatoid arthritis (RA) is a chronic destructive polyarthritis. It affects ∼1% of the population1 and typically manifests in the fourth and fifth decades of life.2–4 Delays in diagnosis and treatment of RA are common and are associated with worse outcomes.5–8 Recently, an increased research effort has been directed towards the ‘at-risk’ phases of RA, prior to the development of clinical signs of joint swelling, to identify those at risk of developing RA and to reduce this risk through the modification of environmental risk factors and pharmacological intervention.9–11

Genetic factors contribute significantly to the risk of RA.12 For seropositive RA, at least half of the risk is conferred by genetic risk factors;13 recent large genetic studies have identified over 100 susceptibility loci.14 ,15 Population-based epidemiological studies have shown that having a family history of RA increases the risk of RA by approximately three to five times,16–18 with the risk being higher in first-degree relatives than second-degree relatives.17 Furthermore, a range of environmental and lifestyle risk factors including occupational exposure to pollutants,19 body mass index,20 periodontitis,21 reproductive factors,22 smoking23 and dietary factors24–26 contribute to the increased risk of developing RA. Some of these environmental risk factors may interact mechanistically with genetic risk factors to increase the risk of RA,27 and others may have familial associations, thus contributing to the familial aggregation of RA.28 ,29

Individuals with genetic and environmental risk factors for RA may progress through a phase associated with the development of systemic autoimmunity (eg, the development of autoantibodies such as rheumatoid factor,30 ,31 anticitrullinated protein/peptide antibodies and anticarbamylated protein antibodies32) before the clinical symptoms and signs of RA manifest.9 It remains unclear whether there are changes detectable within the synovium during the phase of autoantibody positivity prior to the development of joint swelling.33 ,34

Together these data suggest that information related to genotype, environmental exposures and measures of autoimmunity and inflammation may be used to predict RA development in individuals who have not yet developed clinical disease. A potential target population for such testing, with a view to risk stratification and intervention to modulate risk, are the first-degree relatives of individuals with RA. Indeed, a number of ongoing prospective studies are recruiting the first-degree relatives of patients with RA to study disease mechanisms driving the switch to RA,35 to develop predictive algorithms for RA and to test interventions to reduce RA risk.36 While considerable research effort is thus focused on the first-degree relatives of patients with RA, and a qualitative study has gathered data relating to their views of preventive strategies,37 little is known about how such individuals view issues related to their susceptibility to and risk of developing RA, and how willing they would be to be assessed and tested to have this risk quantified. The present qualitative study addresses these issues.

Procedure

Eligible participants were the first-degree relatives (offspring and siblings) of people with RA. Participants were required to be at least 18 years of age and without a diagnosis of inflammatory joint disease.

Patients with RA were approached during routine secondary care clinics in Birmingham (UK), Erlangen (Germany) and Vienna (Austria) and were given a letter to pass on to a first-degree relative of their choosing inviting them to participate in an interview about risk and predictive testing for RA. Participants were recruited between October 2014 and October 2015. It was explained to patients that it was entirely at their discretion whether to pass on the invitation letter. All research participants (ie, the participating first-degree relatives) gave written informed consent prior to interview.

The semistructured interviews were guided by an interview schedule which was informed by a review of the qualitative literature exploring perceptions of risk and testing in those at risk of developing a chronic disease.38 ,39 The interviews aimed to assess personal perceptions of risk; therefore, one-to-one interviews were conducted. In addition, an international multidisciplinary team of healthcare professionals, patient research partners and researchers working on the EuroTEAM project (http://www.team-arthritis.eu) reviewed and redrafted the interview schedule (see box 1 for sample questions from the final interview schedule).

Box 1

Sample interview schedule for those at risk of developing rheumatoid arthritis (RA)

  • Tell me what you know about RA?

  • PROMPTS: What do you think the causes of RA could be? What do you think the risks factors for RA are? Tell me about how serious you think RA is? How would you know you had RA, for example, what symptoms would you expect? What would be the impact of RA on your life? Do you think you would be able to control RA yourself? Do you think there are treatments available that would effectively treat RA?

  • Do you ever worry about the possibility of developing RA in the future?

  • What would you think if you were told that you could have a test that would tell you how likely you were to develop RA?

  • PROMPTS: What sort of information should this test give you? When do you think would be the right time to get this information? How would you feel about the idea of having a test that would tell you your chance of developing RA in the future? In what ways do you think it would be helpful for you to know your chances of developing RA?

  • What would your concerns be if you knew what your risk of developing RA was?

  • What kind of tests do you think people might be able to do to work out whether or not you might develop RA (test that are available now and tests that might become available in the future)?

One-to-one interviews were conducted at local hospitals or by telephone (for those participants who had difficulty in attending the hospital for a face-to-face interview). Interviews lasted between 30 and 90 min and were digitally audio-recorded. In the UK, participants who wanted further information about arthritis were advised to contact Arthritis Research UK, the National Rheumatoid Arthritis Society or the local hospital's Patient Advice and Liaison Service. Participants in Austria and Germany were advised to contact the local rheumatology outpatient clinic.

The interviews were transcribed verbatim. Interviews conducted in German were translated into English following transcription. Transcripts were anonymised and analysed centrally in Birmingham, UK, by RJS.

Analysis procedure

Data collection and analysis were carried out in parallel to assess when thematic saturation of major developing themes had been achieved. The data were analysed using a thematic approach40 facilitated by NVivo (a qualitative software programme) (NVivo qualitative data analysis software; QSR International Pty Version. 8 (2008)). Transcripts were subjected to line-by-line coding by RJS. Patient research partners blind coded three transcripts to develop reliable and inclusive themes informed by multiple perspectives. Discussion of the coding framework took place between researchers and patient research partners. Coding categories that lacked concordance were discussed and absorbed into the coding framework. The initial codes were then grouped into the most noteworthy and frequently occurring categories. The core themes extracted and presented here focus on perceptions of first-degree relatives about their personal risk of RA and their views on being tested.

Results

Thirty-four first-degree relatives of patients with RA participated, 24 from the UK, 3 from Germany and 7 from Austria. Six participants were siblings of a patient with RA, 26 were the adult offspring of a patient with RA and 2 participants had a sibling and a parent with RA. Participants were aged between 23 and 67 years (mean 39 years) and 26 (76%) were women (see table 1 for participant characteristics). Quotations are presented in tables 25 and are referred to in the text using ‘Q’ followed by the quotation code.

Table 1

Details of first-degree relatives of patients with RA who participated in the interviews

Table 2

Quotations related to an understanding of family history and genetic factors as risk factors for rheumatoid arthritis

Table 3

Quotation related to personal considerations of rheumatoid arthritis risk and communication about risk within families

Table 4

Quotations related to perceptions surrounding the use of predictive tests: positive perspectives

Table 5

Quotations related to perceptions surrounding the use of predictive tests: negative perspectives

Understanding of family history and genetic factors as risk factors for RA

The first-degree relatives of people with RA understood that there was a hereditary component to RA (Q1), and often used the word ‘genetic’ to describe the cause of their increased risk (Q2). First-degree relatives (from here on referred to as ‘relatives’) recognised that they were more susceptible to developing RA than second-degree relatives (Q3). Interestingly, some felt that they were more susceptible to developing RA than other first-degree relatives because they appeared to follow other patterns of illness displayed by their relative with RA (Q4). Additional biological factors, such as being women and some environmental factors, were also described as playing a role in the development of RA (Q2 and Q5).

When considering their perceived personal susceptibility, relatives reported that there were aspects of familial risk, particularly genetic susceptibility, which they found difficult to understand. One relative felt that effectively communicating an understanding of genetic risk to the public was extremely challenging (Q6). Others felt that they needed more information about their level of risk as a relative and the specific role that genes associated with RA played in this risk (Q7).

When considering their susceptibility to RA, relatives voiced their concerns about the future, and how being at risk of developing RA was a worry for them. Those who had considered their personal susceptibility to RA described being fearful of what they may uncover if they were to have their risk quantified. For some, the prospect of living with RA would entail great amounts of uncertainty (Q8). For many, having witnessed the impact of RA on their sibling/parent heightened the worry they felt in relation to the possibility of developing RA themselves in the future (Q9). Interestingly, a small number of relatives had experienced joint-related symptoms but had not yet sought medical advice, being fearful of the potential outcome (Q10).

Personal considerations of RA risk and communication about risk within families

Relatives discussed knowing little about RA or its risk factors, feeling that they had been ‘shielded’ or ‘protected’ from this knowledge by their sibling/parent (Q11). Also, relatives described how they rarely discussed RA within their family unit, and in some cases, the invitation to participate in this study was the first time that the opportunity to discuss RA, and its risk had emerged (Q12). For one relative, receiving the invitation to take part in this study facilitated the first conversation he had had with his father about RA (Q13). Another described how his mother had had some concerns about him taking part in this study, because of the worry which discussing issues surrounding risk and predictive testing may cause (Q14). One relative described how her brother had been asked to take part in this study, but ignored the request; her mother had then approached her and encouraged her to participate (Q15). This relative suggested that it was her attitude towards health which set her apart from her brother.

Most relatives had not fully considered issues related to their personal susceptibility to RA prior to being approached to take part in this study (Q16). Some relatives indicated that taking part in this study had been a positive experience for them and had provided them with much needed knowledge, a chance for reflection on their risk and a greater understanding of RA and how it affected their sibling/parent (Q17). However, others described how they would prefer to avoid considering their personal risk of RA to avoid experiencing worry or anxiety about the future (Q18).

Perceptions surrounding the use of predictive tests: positive perspectives

Most relatives were in favour of the basic principle behind predictive testing—identifying those at risk and quantifying the level of risk (Q19). It was also felt that the information gained from predictive testing could be acted on to reduce the future risk of developing RA (Q20). In particular, relatives recognised the importance of early intervention, and they were aware that testing could put them ‘on alert’ for the early symptoms of RA (Q21) or suggested that they might be able to take preventive treatment (Q22). Many relatives felt that it was important to know that they were at risk and that information related to their actual risk would be of value to them, allowing them to ‘mentally’ prepare for the future (Q23). Others could see the benefit of preparing for the functional limitations that may be associated with RA (Q24). A few had already undertaken predictive testing to explore their personal risk of developing RA (Q25). Some were willing to be tested for altruistic reasons such as taking part in research (Q26).

Perceptions surrounding the use of predictive tests: negative perspectives

The ability of predictive tests to quantify risk was widely discussed (Q27), with one participant questioning the specificity and sensitivity of the test (Q28). Relatives expressed a desire for tests that would, with a very high likelihood, be able to confirm or exclude the fact that they would develop RA (Q29). However, many relatives suspected that test results would give them an intermediate risk of developing RA and others highlighted concerns about ‘false-positive’ results (Q30). Some believed that predictive testing would not be able to give them answers to questions they thought were important, for example, how severe would their RA be were they to develop it, and when it would be most likely to begin (Q31).

Relatives were worried about the impact of testing on their family members and in particular on their sibling/parent with RA (Q32). Participants felt that seeking information about risk and pursuing testing would cause their relative with RA to experience stress, worry or feelings of guilt. Participants were further worried about the stress that predictive test results may cause them. One even suggested that such stress could cause the disease to develop earlier than it otherwise would (Q33).

Relatives felt that being given risk information when they were young would be a particular burden (Q34). Instead, they felt that testing should be left until later in life, when the chance of developing a condition like RA was higher. Risk information was considered to have significant implications for future life choices and could make them ‘rush’ through life (Q35). One relative suggested that such information could bring forward major life decisions, such as having children (Q36).

Some relatives reflected on previous negative personal experiences of having received poorly communicated test-related information (Q37). For some, the approach to the delivery of risk information represented an important feature of a predictive test and may determine whether the test would be acceptable to them. Relatives discussed how they would want to be told prior to the test what format the result would take. Some suggested that they would like to receive the results by letter, and then be given the opportunity to discuss the results with a healthcare professional (Q38). Other relatives emphasised the importance of talking to someone about the test result, especially to manage the psychological distress that may be associated with receiving a ‘positive’ test result (Q39). Many relatives felt that there was a need for ongoing support from a healthcare professional following testing (Q40).

Discussion

This study explored the degree to which first-degree relatives of people with RA felt that they were susceptible to developing RA and their perceptions of predictive testing. Most relatives were aware that there was a genetic contribution to the risk of RA and that they may be susceptible to developing RA; however, they were unsure of the extent of the additional risk. Relatives highlighted the need for additional information about familial risk and described the need for better communication strategies in relation to imparting this information.

Generally, first-degree relatives felt that there was a need for more information and support specifically designed for the family members of people with RA. The current lack of support and information was suggested to have a number of effects, including family members not feeling able to communicate and support the person affected with RA and not feeling able to understand concepts surrounding the nature of RA and the risks associated with RA. Studies of information sharing among family members at risk of cancer have found that patients with the disease do not always communicate risk information in a timely or thorough fashion.41 Forrest et al42 found that relatives from smaller families, and female relatives, were more likely to make contact with genetic services. Research has shown that genetic counselling can facilitate interfamily communication and can help to minimise distress and increase the number of family members making contact with health services to be tested.43 ,44

An incidental finding of this research was that being invited to take part in research about risk was the first time that some relatives had fully considered their personal susceptibility to RA. In some cases, this exposure was viewed positively, but in other cases, it caused worry and concern. It is difficult to draw conclusions about the specific impact taking part in this study had on relatives' well-being, but we note that relatives did indicate that support mechanisms would be helpful to enable them to understand and cope with risk-related information, especially if predictive testing were to be offered. We would suggest that researchers accessing participants in ‘at-risk’ populations pay particular attention to the impact that an invitation to participate and participation itself may have, and offer additional support to, mitigate against anxiety caused. While personal susceptibility may not have been considered, perceptions of RA severity may predict personal willingness to engage in predictive testing. It is possible that first-degree relatives of people with more severe forms of RA or poorly controlled disease maybe more motivated to engage in predictive testing. This would be in line with the predictions of the health belief model.45 A quantitative investigation to assess the effect of factors such as disease severity in people with RA, on their family members' perceptions of risk and orientation towards predictive testing, is needed to test this hypothesis.

In addition, it became apparent during the course of this study that some relatives were symptomatic but had not yet sought medical help. Detailed information on the health status of the participating relatives was not gathered within this study, but those who were symptomatic were advised to speak to their family physician and were given details of resources for obtaining additional information. However, the symptomatic nature of some relatives raises important issues surrounding informing relatives about risk, and the importance of seeking help quickly should symptoms emerge. While some relatives were aware that their symptoms may be indicative of the early stages of RA, and were worried about what information would be revealed to them if they sought help, few were aware of the importance of early intervention. Where information about the benefits of early intervention in preventing joint destruction made available to them, it is possible that their attitude to help-seeking may have been different.

This study has a number of limitations. First, our access to first-degree relatives was via patients with RA. Some relatives described how they were chosen in preference to other relatives, who would either worry too much or not be receptive to discussing issues related to risk. The findings presented may thus not fully reflect the range of views related to risk and testing held by first-degree relatives. This potential limitation highlights the need to fully understand the barriers that patients with RA face when discussing issues of risk with family members. A second limitation of this research was that the majority of participants were women. A criticism of many qualitative studies in the field of RA is that the male perspective is under-represented.8 While the female:male ratio of RA is typically 2:1, it is essential that studies attempt to include the views of more male participants. Therefore, we acknowledge that themes related to gender and male perspectives of risk and predictive testing did not reach saturation and are not represented in our data. A final limitation is that only a small number of individuals from ethnic-minority communities were interviewed; therefore, a full understanding of the cultural barriers to predictive testing was not achieved.

Besides these limitations, this study has a number of strengths. Relatives were sampled from centres in three different European countries and saturation of the main themes was achieved by combining interview data from all centres; furthermore, no differences in the views expressed by relatives sampled from different European countries were detected. Gathering data from multiple countries means that interventions developed based on these data are likely to be relevant in multiple contexts. A further strength of this study was the support given by an international panel of patient research partners who advised researchers and acted as coresearchers.

Identifying individuals at risk of RA may allow targeted interventions to reduce the risk and consequence of future disease; however, our data show that relatives have concerns about predictive testing and risk information that would result from it (the key messages of this study are summarised in box 2). The future development of strategies to quantify and communicate risk needs to take these views into account and incorporate approaches to mitigate concerns and minimise any negative psychological impact of risk information.

Box 2

Key messages

  • Identifying those at risk of rheumatoid arthritis (RA), and quantifying their risk, may help guide targeted interventions to reduce future disease burden. This qualitative study found that first-degree relatives of people with RA, who are themselves at an enhanced risk of RA, had a number of concerns in relation to predictive testing.

  • Some relatives would be unwilling to undergo predictive testing and were worried about the psychological impact of risk information. Others were more receptive and recognised that such information could facilitate the development and implementation of preventive strategies as well as encouraging prompt help-seeking and intervention at the onset of RA symptoms.

  • Developing strategies that communicate risk information effectively while reducing the psychological burden associated with this information is essential.

Acknowledgments

The authors thank the EuroTEAM Patient Research Partners Panel for their involvement in this research.

References

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Footnotes

  • Contributors All authors made a substantial contribution to study conception and design. RJS, MS, ME, EM and KK collected the data. RJS analysed and interpreted data. All authors were involved in drafting the article, revised it and approved the final version of the article.

  • Funding This work was supported by European Union within the FP7 HEALTH programme under the grant agreement FP7-HEALTH-F2-2012-305549 (EuroTEAM) and by Riksbankens Jubileumsfond (The Swedish Foundation for Humanities and Social Sciences) under Grant M13-0260:1 ‘Mind the Risk’.

  • Competing interests None declared.

  • Ethics approval Ethical approval was obtained in the UK from the HumberBridge National Research Ethics Committee, in Austria from the Ethics Committee of the Medical University of Vienna and in Germany from the Ethics committee of the University of Erlangen-Nuremberg.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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