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Background: The value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development., Methods: A 12-month "accelerator" award facilitated development of a substantive funding application to deliver the Rheumatoid Arthritis Prevention PlatfORm Trial (RAPPORT), conceived to prioritise preventative interventions for people at risk of RA. PPI partners, including individuals at risk of rheumatoid arthritis (RA), RA patients, relatives and members of the public, provided feedback on key trial design issues through online meetings, a feedback form and emails. PPI processes employed during the one-year accelerator project were thereafter evaluated by PPI partners using an anonymous online feedback form with reference to National Institute of Health and Care Research (NIHR) UK standards for public involvement in research., Results: Sixteen out of the 25-strong PPI partner panel completed an online feedback form (64%). Respondents perceived PPI processes positively in relation to all NIHR standard domains. Several key facilitators and challenges were identified, including the need for adequate PPI funding during pre-award phases of research, strategies for creating an inclusive environment, flexibility around levels of involvement, and challenges in achieving representatively diverse participation, and the importance of communicating transparent processes for role-assignment and time-reimbursement., Conclusions: In general, RAPPORT was considered an example of PPI well done, and in line with UK standards for public involvement in research. Facilitators and challenges of relevance for the development of future translational and clinical trial funding applications are highlighted., (© 2024. The Author(s).)

Background: Since the publication of the 2011 European Alliance of Associations for Rheumatology (EULAR) recommendations for patient research partner (PRP) involvement in rheumatology research, the role of PRPs has evolved considerably. Therefore, an update of the 2011 recommendations was deemed necessary., Methods: In accordance with the EULAR Standardised Operational Procedures, a task force comprising 13 researchers, 2 health professionals and 10 PRPs was convened. The process included an online task force meeting, a systematic literature review and an in-person second task force meeting to formulate overarching principles (OAPs) and recommendations. The level of agreement of task force members was assessed anonymously (0-10 scale)., Results: The task force developed five new OAPs, updated seven existing recommendations and formulated three new recommendations. The OAPs address the definition of a PRP, the contribution of PRPs, the role of informal caregivers, the added value of PRPs and the importance of trust and communication in collaborative research efforts. The recommendations address the research type and phases of PRP involvement, the recommended number of PRPs per project, the support necessary for PRPs, training of PRPs and acknowledgement of PRP contributions. New recommendations concern the benefits of support and guidance for researchers, the need for regular evaluation of the patient-researcher collaboration and the role of a designated coordinator to facilitate collaboration. Agreements within the task force were high and ranged between 9.16 and 9.96., Conclusion: The updated EULAR recommendations for PRP involvement are more substantially based on evidence. Together with added OAPs, they should serve as a guide for researchers and PRPs and will ultimately strengthen the involvement of PRPs in rheumatology research., Competing Interests: Competing interests: MdW: over the last 3 years, Stichting Tools has received fees for lectures or consultancy provided by Maarten de Wit from UCB, not related to this project. LG reports grants from AbbVie, Biogen, Lilly, Novartis, UCB, personal fees from AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, non-financial support from AbbVie, Amgen, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB, outside the submitted work. KA: funded by EULAR grant RES005 this project; research grants: UCB; consulting fees: Novartis. ME: congress travel support from Janssen and AstraZeneca outside of the submitted work. DB: Speakers bureau: AbbVie, BMS, Galapagos, Janssen, Lilly, MSD. Research grants: Novartis. Consultancy: Sandoz, UCB. Part-time work in Savana Research. EFM has received consultancy fees from Boehringer Ingelheim Portugal outside of the submitted work, LPCDR has received fees for lectures or consultancy provided by Elsa Mateus from Lilly Portugal, GSK and Novartis, outside of the submitted work. SWT has received research funding, consultancy and/ or speaker fees from: Abbvie, Arthrogen, AstraZeneca, BMS, Celgene, Galapagos, Galvani bioelectronics, GSK, Lilly, MSD, Pfizer, Roche, and Sanofi-Genzyme, all outside the submitted work. WT has received research funding, consultancy and/ or speaker fees from: AbbVie, Amgen, BMS, Celgene, Eli-Lilly, GSK, Janssen, MSD, Novartis, Ono-Pharma, Pfizer and UCB all outside of the submitted work. HB, SB, PB, JP, CD, MF, SK, UK, DPR, JR-C, JS, RS, SRS, AV, T-CW, CZ and JP report no competing interests for this project., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these "at-risk" stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA., Methods: Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables., Results: Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, "mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations." In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs., Conclusions: Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages., (© 2024. The Author(s).)

Objectives: To assess whether prodromal symptoms of rheumatoid arthritis (RA), as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status., Methods: A cross-sectional study to determine the coding of common symptoms (≥0.1% in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between January 1st 2004 to May 1st 2022. Eligible cases were adults with a code for RA diagnosis. For each symptom, a logistic regression was performed with the symptom as dependent variable, and ethnicity and socioeconomic status as independent variables. Results were adjusted for sex, age, BMI, and smoking status. White ethnicity and the highest socioeconomic quintile were comparators., Results: In total, 70115 cases were eligible for inclusion, of which 66.4% female. Twenty-one symptoms were coded in > 0.1% of cases so were included in the analysis. Patients of South Asian ethnicity had higher frequency of codes for several symptoms, with the largest difference by odds ratio being muscle cramps (OR 1.71, 1.44-2.57) and shoulder pain (1.44, 1.25-1.66). Patients of Black ethnicity had higher prevalence of several codes including unintended weight loss (2.02, 1.25-3.28) and ankle pain (1.51, 1.02-2.23). Low socioeconomic status was associated with morning stiffness (1.74, 1.08-2.80) and falls (1.37, 2.03-1.82)., Conclusion: There are significant differences in coded symptoms between demographic groups, which must be considered in clinical practice in diverse populations and to avoid algorithmic bias in prediction tools derived from routinely collected healthcare data., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background and Objective: There has been an increase in the study and use of stated-preference methods to inform medicine development decisions. The objective of this study was to identify prioritized topics and questions relating to health preferences based on the perspective of members of the preference research community., Methods: Preference research stakeholders from industry, academia, consultancy, health technology assessment/regulatory, and patient organizations were recruited using professional networks and preference-targeted e-mail listservs and surveyed about their perspectives on 19 topics and questions for future studies that would increase acceptance of preference methods and their results by decision makers. The online survey consisted of an initial importance prioritization task, a best-worst scaling case 1 instrument, and open-ended questions. Rating counts were used for analysis. The best-worst scaling used a balanced incomplete block design., Results: One hundred and one participants responded to the survey invitation with 66 completing the best-worst scaling. The most important research topics related to the synthesis of preferences across studies, transferability across populations or related diseases, and method topics including comparison of methods and non-discrete choice experiment methods. Prioritization differences were found between respondents whose primary affiliation was academia versus other stakeholders. Academic researchers prioritized methodological/less studied topics; other stakeholders prioritized applied research topics relating to consistency of practice., Conclusions: As the field of health preference research grows, there is a need to revisit and communicate previous work on preference selection and study design to ensure that new stakeholders are aware of this work and to update these works where necessary. These findings might encourage discussion and alignment among different stakeholders who might hold different research priorities. Research on the application of previous preference research to new contexts will also help increase the acceptance of health preference information by decision makers., (© 2023. The Author(s).)

Background: When selecting samples for patient preference studies, it may be difficult or impractical to recruit participants who are eligible for a particular treatment decision. However, a general public sample may not be an appropriate proxy., Objective: This study compares preferences for rheumatoid arthritis (RA) preventive treatments between members of the general public and first-degree relatives (FDRs) of confirmed RA patients to assess whether a sample of the general public can be used as a proxy for FDRs., Methods: Participants were asked to imagine they were experiencing arthralgia and had screening tests indicating a 60% chance of developing RA within 2 yrs. Using a discrete choice experiment, participants were offered a series of choices between no treatment and 2 unlabeled hypothetical treatments to reduce the risk of RA. To assess data quality, time to complete survey sections and comprehension questions were assessed. A random parameter logit model was used to obtain attribute-level estimates, which were used to calculate relative importance, maximum acceptable risk (MAR), and market shares of hypothetical preventive treatments., Results: The FDR sample ( n  = 298) spent more time completing the survey and performed better on comprehension questions compared with the general public sample ( n  = 982). The relative importance ranking was similar between the general public and FDR participant samples; however, other relative preference measures involving weights including MARs and market share differed between groups, with FDRs having numerically higher MARs., Conclusion: In the context of RA prevention, the general public (average risk) may be a reasonable proxy for a more at-risk sample (FDRs) for overall relative importance ranking but not weights. The rationale for a proxy sample should be clearly justified., Highlights: Participants from the general public were compared to first-degree relatives on their preferences for rheumatoid arthritis (RA) preventive treatments using a discrete choice experiment.Preferences were similar between groups in terms of the most important and least important attributes of preventive treatments, with effectiveness being the most important attribute. However, relative weights differed.Attention to the survey and predicted market shares of hypothetical RA preventive treatments differed between the general public and first-degree relatives.The general public may be a reasonable proxy for an at-risk group for patient preferences ranks but not weights in the disease prevention context; however, care should be taken in sample selection for patient preference studies when choosing nonpatients., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Rachael DiSantostefano is employed by Janssen Research and Development, LLC, and is a stockholder in Johnson & Johnson. J. Veldwijk, Gwenda Simons, K. Schölin Bywall, Marie Falahee, Jennifer Humphreys, and Ian Bruce declared no conflict of interest. Karim Raza declared personal fees from Abbvie and Sanofi and grant/research support from Bristol Myers Squibb. Matthias Englbrecht declared personal fees from AbbVie, Chugai, Eli Lilly, Novartis, Roche, Sanofi, and Mundipharma and grant/research support from Roche and Chugai. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided in part by a grant the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement No. 115966. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations (EFPIA). K. Raza is supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. This article and its contents reflect the view of the authors and not the view of PREFER, IMI, the European Union, or EFPIA.

Objective: We aimed to empirically compare maximum acceptable risk results estimated using both a discrete choice experiment (DCE) and a probabilistic threshold technique (PTT)., Methods: Members of the UK general public (n = 982) completed an online survey including a DCE and a PTT (in random order) measuring their preferences for preventative treatment for rheumatoid arthritis. For the DCE, a Bayesian D-efficient design consisting of four blocks of 15 choice tasks was constructed including six attributes with varying levels. The PTT used identical risk and benefit attributes. For the DCE, a panel mixed-logit model was conducted, both mean and individual estimates were used to calculate maximum acceptable risk. For the PTT, interval regression was used to calculate maximum acceptable risk. Perceived complexity of the choice tasks and preference heterogeneity were investigated for both methods., Results: Maximum acceptable risk confidence intervals of both methods overlapped for serious infection and serious side effects but not for mild side effects (maximum acceptable risk was 32.7 percent-points lower in the PTT). Although, both DCE and PTT tasks overall were considered easy or very easy to understand and answer, significantly more respondents rated the DCE choice tasks as easier to understand compared with those who rated the PTT as easier (7-percentage point difference; p < 0.05)., Conclusions: Maximum acceptable risk estimate confidence intervals based on a DCE and a PTT overlapped for two out of the three included risk attributes. More respondents rated the DCE as easier to understand. This may suggest that the DCE is better suited in studies estimating maximum acceptable risk for multiple risk attributes of differing severity, while the PTT may be better suited when measuring heterogeneity in maximum acceptable risk estimates or when investigating one or more serious adverse events., (© 2023. The Author(s).)

Background: There is increasing research interest in the development of preventive treatment for individuals at risk of rheumatoid arthritis (RA). Previous studies have explored the perceptions of at-risk groups and patients about predictive and preventive strategies for RA, but little is known about health care professionals' (HCPs) perspectives., Methods: One-to-one semi-structured qualitative interviews were conducted (face-to-face or by telephone) with HCPs. Audio recordings of the interviews were transcribed, and the data were analysed by thematic analysis., Results: Nineteen HCPs (11 female) were interviewed, including ten GPs, six rheumatologists and three rheumatology nurse specialists. The thematic analysis identified four organising themes: 1) Attributes of predictive and preventive approaches; 2) Ethical and psychological concerns; 3) Implementation issues and 4) Learning from management of other conditions. Theme 1 described necessary attributes of predictive and preventive approaches, including the type and performance of predictive tools, the need for a sound evidence base and consideration of risks and benefits associated with preventive treatment. Theme 2 described the ethical and psycho-social concerns that interviewees raised, including the potential negative economic, financial and psychological effects of risk disclosure for 'at-risk' individuals, uncertainty around the development of RA and the potential for benefit associated with the treatments being considered. Theme 3 describes the implementation issues considered, including knowledge and training needs, costs and resource implications of implementing predictive and preventive approaches, the role of different types of HCPs, guidelines and tools needed, and patient characteristics relating to the appropriateness of preventive treatments. Theme 4 describes lessons that could be learned from interviewees' experiences of prediction and prevention in other disease areas, including how preventive treatment is prescribed, existing guidelines and tools for other diseases and issues relating to risk communication., Conclusions: For successful implementation of predictive and preventative approaches in RA, HCPs need appropriate training about use and interpretation of predictive tools, communication of results to at-risk individuals, and options for intervention. Evidence of cost-efficiency, appropriate resource allocation, adaptation of official guidelines and careful consideration of the at-risk individuals' psycho-social needs are also needed., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: While the integration of patient and public involvement (PPI) in clinical research is now widespread and recommended as standard practice, meaningful PPI in pre-clinical, discovery science research is more difficult to achieve. One potential way to address this is by integrating PPI into the training programmes of discovery science postgraduate doctoral students. This paper describes the development and formative evaluation of the Student Patient Alliance (SPA), a programme developed at the University of Birmingham that connects PPI partners with doctoral students., Methods: Following a successful pilot of the SPA by the Rheumatology Research Group at the University of Birmingham, the scheme was implemented across several collaborating Versus Arthritis / Medical Research Council (MRC) centres of excellence. Doctoral students were partnered with PPI partners, provided with initial information and guidance, and then encouraged to work together on research and public engagement activities. After six months, students, their PPI partners and the PPI coordinators at each centre completed brief surveys about their participation in the SPA., Results: Both doctoral students and their PPI partners felt that taking part in SPA had a positive impact on understanding, motivation and communication skills. Students reported an increased understanding of PPI and patient priorities and reported improved public engagement skills. Their PPI partners reported a positive impact of the collaboration with the students. They enjoyed learning about the student's research and contributing to the student's personal development. PPI coordinators also highlighted the benefits of the SPA, but noted some challenges they had experienced, such as difficulties matching students with PPI partners., Conclusions: The SPA was valued by students and PPI partners, and it is likely that initiatives of this kind would enhance students' PPI and public engagement skills and awareness of patients' experiences on a wider scale. However, appropriate resources are needed at an institutional level to support the implementation of effective programmes of this kind on a larger scale., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: There is a need to better define symptom characteristics associated with arthritis development in individuals at risk of rheumatoid arthritis (RA). We investigated whether reported symptoms in at-risk individuals could predict arthritis development and whether predictive symptoms differed between seropositive and seronegative at-risk individuals., Method: At-risk individuals from four cohorts (Netherlands, UK, Sweden, and Switzerland) completed the Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire. Participants had either (i) anti-citrullinated protein antibodies and/or rheumatoid factor, or (ii) relevant symptoms with or without RA antibodies. Follow up was ≥ 24 months or until clinical arthritis development. Stepwise forward selection created SPARRA prediction models for the combined group and for a seropositive subgroup., Results: Of 214 participants, the mean age was 50 years, 67% were female, and 27% (n = 58) developed clinical arthritis after a median time of 7 months. Four symptoms predicted arthritis development: self-reported joint swelling, joint pain moving from side to side (combined group only), feeling pins and needles in the joints, and often feeling fatigued (predicting non-arthritis)., Conclusion: Specific symptoms can provide useful information to estimate a person's RA risk. Differences in predictive symptoms between seropositive and seronegative at-risk individuals need to be further investigated. Future research is needed to determine whether changes in symptoms over time improve prediction and to determine the value of SPARRA in optimizing the selection of individuals who need to consult a rheumatologist.

Objective: Some immunomodulatory drugs have been shown to delay the onset of, or lower the risk of developing, rheumatoid arthritis (RA), if given to individuals at risk. Several trials are ongoing in this area; however, little evidence is currently available about the views of those at risk of RA regarding preventive treatment., Method: Three focus groups and three interviews explored factors that are relevant to first degree relatives (FDRs) of RA patients and members of the general public when considering taking preventive treatment for RA. The semi-structured qualitative interview prompts explored participant responses to hypothetical attributes of preventive RA medicines. Transcripts of focus group/interview proceedings were inductively coded and analysed using a framework approach., Results: Twenty-one individuals (five FDRs, 16 members of the general public) took part in the study. Ten broad themes were identified describing factors that participants felt would influence their decisions about whether to take preventive treatment if they were at increased risk of RA. These related either directly to features of the specific treatment or to other factors, including personal characteristics, attitude towards taking medication, and an individual's actual risk of developing RA., Conclusion: This research highlights the importance of non-treatment factors in the decision-making process around preventive treatments, and will inform recruitment to clinical trials as well as information to support shared decision making by those considering preventive treatment. Studies of treatment preferences in individuals with a confirmed high risk of RA would further inform clinical trial design.

First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) are increasingly recruited to prediction and prevention studies. Access to FDRs is usually via their proband with RA. Quantitative data on predictors of family risk communication are lacking. RA patients completed a questionnaire assessing likelihood of communicating RA risk information to their FDRs, demographic variables, disease impact, illness perceptions, autonomy preferences, interest in FDRs taking a predictive test for RA, dispositional openness, family functioning, and attitudes towards predictive testing. Ordinal regression examined associations between patients' characteristics and their median likelihood of communicating RA risk to FDRs. Questionnaires were completed by 482 patients. The majority (75.1%) were likely/extremely likely to communicate RA risk information to FDRs, especially their children. Decision-making preferences, interest in FDRs taking a predictive test, and beliefs that risk knowledge would increase people's empowerment over their health increased patients' odds of being likely to communicate RA risk information to FDRs. Beliefs that risk information would cause stress to their relatives decreased odds that patients would be likely to communicate RA risk. These findings will inform the development of resources to support family communication about RA risk., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: IW, DZ, GS, RJS, KR and MF declare they have no competing interests. CDM is funded by the National Institute for Health Research (NIHR) Applied Research Collaboration West Midlands, the National Institute for Health Research (NIHR) School for Primary Care Research and a National Institute for Health Research (NIHR) Research Professorship in General Practice (NIHR-RP-2014–04-026) for this research project. The School of Medicine has received financial support from BMS for an unrelated non-pharmacological study screening patients for AF in primary care., (Copyright © 2023. Published by Elsevier B.V.)

Background: Clinical trial design requires value judgements and understanding patient preferences may help inform these judgements, for example when prioritizing treatment candidates, designing complex interventions, selecting appropriate outcomes, determining clinically important thresholds, or weighting composite outcomes. Preference elicitation methods are quantitative approaches that can estimate patients' preferences to quantify the absolute or relative importance of outcomes or other attributes relevant to the decision context. We aimed to explore stakeholder perceptions of using preference elicitation methods to inform judgements when designing clinical trials in rheumatology., Methods: We conducted 1-on-1 semi-structured interviews with patients with rheumatic diseases and rheumatology clinicians/researchers, recruited using purposive and snowball sampling. Participants were provided pre-interview materials, including a video and a document, to introduce the topic of preference elicitation methods and case examples of potential applications to clinical trials. Interviews were conducted via Zoom and were audio-recorded and transcribed. We used thematic analysis to analyze our data., Results: We interviewed 17 patients and 9 clinicians/researchers, until data and inductive thematic saturation were achieved within each group. Themes were grouped into overall perceptions, barriers, and facilitators. Patients and clinicians/researchers generally agreed that preference elicitation studies can improve clinical trial design, but that many considerations are required around preference heterogeneity and feasibility. A key barrier identified was the additional resources and expertise required to measure and incorporate preferences effectively in trial design. Key facilitators included developing guidance on how to use preference elicitation to inform trial design, as well as the role of external decision-makers in developing such guidance, and the need to leverage the movement towards patient engagement in research to encourage including patient preferences when designing trials., Conclusion: Our findings allowed us to consider the potential applications of patient preferences in trial design according to stakeholders within rheumatology who are involved in the trial process. Future research should be conducted to develop comprehensive guidance on how to meaningfully include patient preferences when designing clinical trials in rheumatology. Doing so may have important downstream effects for shared decision-making, especially given the chronic nature of rheumatic diseases., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To quantify preferences for preventive therapies for rheumatoid arthritis (RA) across three countries., Methods: A web-based survey including a discrete choice experiment was administered to adults recruited via survey panels in the UK, Germany and Romania. Participants were asked to assume they were experiencing arthralgia and had a 60% chance of developing RA in the next 2 years and completed 15 choices between no treatment and two hypothetical preventive treatments. Treatments were defined by six attributes (effectiveness, risks and frequency/route of administration) with varying levels. Participants also completed a choice task with fixed profiles reflecting subjective estimates of candidate preventive treatments. Latent class models (LCMs) were conducted and the relative importance of attributes, benefit-risk trade-offs and predicted treatment uptake was subsequently calculated., Results: Completed surveys from 2959 participants were included in the analysis. Most participants preferred treatment over no treatment and valued treatment effectiveness to reduce risk more than other attributes. A five-class LCM best fitted the data. Country, perceived risk of RA, health literacy and numeracy predicted class membership probability. Overall, the maximum acceptable risk for a 40% reduction in the chance of getting RA (60% to 20%) was 21.7%, 19.1% and 2.2% for mild side effects, serious infection and serious side effects, respectively. Predicted uptake of profiles reflecting candidate prevention therapies differed across classes., Conclusion: Effective preventive pharmacological treatments for RA were acceptable to most participants. The relative importance of treatment attributes and likely uptake of fixed treatment profiles were predicted by participant characteristics., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To define variables associated with perceived risk of developing rheumatoid arthritis (RA) in first-degree relatives (FDRs) of patients with RA., Methods: Patients with RA and their FDRs were invited to complete cross-sectional surveys. FDR and index patient responses were linked. FDRs' perceived absolute risk, comparative risk, experiential risk and worry about risk were assessed using 5-point Likert scales. FDR predictor variables included demographics, illness perceptions and psychosocial variables. Patient predictors of FDR perceived risk were assessed. Binary logistic regression examined the relationship between FDR characteristics and perceived risk of RA. Generalised estimating equations assessed whether patient variables predicted FDR's perceived risk., Results: 396 FDRs returned a survey. 395 FDRs provided sufficient data and were included in analysis. Paired data from 213 patients were available for 291 of these FDRs. All measures of perceived risk were inter-correlated. 65.2% of FDRs perceived themselves to be 'likely' or 'very likely' to develop RA in their lifetime. Relationship with index patient, high health anxiety, female gender, long perceived RA duration, high perceived concern about RA, negative perceived emotional impact of RA and low perceptions of how well treatment would control RA were all associated with increased FDRs' perceived risk. Patient characteristics did not associate with FDRs' risk perceptions., Conclusions: FDRs' perceived risk of RA was high. Key predictors included being a child of a patient with RA, higher health anxiety and lower perceptions of RA treatment control. An understanding of these predictors will inform the development of tailored risk communication resources and preventive clinical strategies for RA., Competing Interests: Competing interests: SB, IW, DZ, GS, KR and MF declare they have no competing interests. CDM is funded by the National Institute for Health Research (NIHR) Applied Research Collaboration West Midlands, the National Institute for Health Research (NIHR) School for Primary Care Research and a National Institute for Health Research (NIHR) Research Professorship in General Practice (NIHR-RP-2014-04-026) for this research project. The School of Medicine has received financial support for a non-pharmacological study screening patients for AF in primary care., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To quantify tolerance to risks of preventive treatments among first-degree relatives (FDRs) of patients with rheumatoid arthritis (RA)., Methods: Preventive treatments for RA are under investigation. In a preference survey, adult FDRs assumed a 60% chance of developing RA within 2 years and made choices between no treatment and hypothetical preventive treatment options with a fixed level of benefit (reduction in chance of developing RA from 60% to 20%) and varying levels of risks. Using a probabilistic threshold technique, each risk was increased or decreased until participants switched their choice. Perceived risk of RA, health literacy, numeracy, Brief Illness Perception Questionnaire and Beliefs about Medicines Questionnaire-General were also assessed. Maximum acceptable risk (MAR) was summarised using descriptive statistics. Associations between MARs and participants' characteristics were assessed using interval regression with effects coding., Results: 289 FDRs (80 male) responded. The mean MAR for a 40% reduction in chance of developing RA was 29.08% risk of mild side effects, 9.09% risk of serious infection and 0.85% risk of a serious side effect. Participants aged over 60 years were less tolerant of serious infection risk (mean MAR ±2.06%) than younger participants. Risk of mild side effects was less acceptable to participants who perceived higher likelihood of developing RA (mean MAR ±3.34%) and more acceptable to those believing that if they developed RA it would last for a long time (mean MAR ±4.44%)., Conclusions: Age, perceived chance of developing RA and perceived duration of RA were associated with tolerance to some risks of preventive RA therapy., Competing Interests: Competing interests: GS, JV, LVM, JHH, INB, and MF have no competing interests. EMJ and RLD are employed by Janssen Research and Development and are stockholders in Johnson & Johnson. ME: speakers bureau: AbbVie, Janssen and Sanofi; paid instructor for AbbVie, Chugai and Roche; consultant for AbbVie, Roche and Sanofi. CR is employed by and a shareholder of Eli Lilly and Company. BH is employed by Pfizer and holds stock or stock options in Pfizer. KR declares personal fees from AbbVie and Sanofi, and grant/research support from Bristol Myers Squibb., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Tests to predict the development of chronic diseases in those with a family history of the disease are becoming increasingly available and can identify those who may benefit most from preventive interventions. It is important to understand the acceptability of these predictive approaches to inform the development of tools to support decision making. Whilst data are lacking for many diseases, data are available for ischemic heart disease (IHD). Therefore, this study investigates the willingness of those with a family history of IHD to take a predictive test, and the effect of the test results on risk-related behaviours., Method: Medline, EMBASE, PsycINFO, LILACS and grey literature were searched. Primary research, including adult participants with a family history of IHD, and assessing a predictive test were included. Qualitative and quantitative outcomes measuring willingness to take a predictive test and the effect of test results on risk-related behaviours were also included. Data concerning study aims, participants, design, predictive test, intervention and findings were extracted. Study quality was assessed using the Standard Quality Assessment Criteria for Evaluating Research Papers from a Variety of Fields and a narrative synthesis undertaken., Results: Five quantitative and two qualitative studies were included. These were conducted in the Netherlands (n = 1), Australia (n = 1), USA (n = 1) and the UK (n = 4). Methodological quality ranged from moderate to good. Three studies found that most relatives were willing to take a predictive test, reporting family history (n = 2) and general practitioner (GP) recommendation (n = 1) as determinants of interest. Studies assessing the effect of test results on behavioural intentions (n = 2) found increased intentions to engage in physical activity and smoking cessation, but not healthy eating in those at increased risk of developing IHD. In studies examining actual behaviour change (n = 2) most participants reported engaging in at least one preventive behaviour, particularly medication adherence., Conclusion: The results suggests that predictive approaches are acceptable to those with a family history of IHD and have a positive impact on health behaviours. Further studies are needed to provide a comprehensive understanding of predictive approaches in IHD and other chronic conditions., (© 2022. The Author(s).)

Background: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis which can cause joint damage and reduced quality of life. Early treatment of RA within 3 months of symptom onset is associated with improved clinical outcomes. However, this window of opportunity is often missed. One important contributing factor is patients with symptoms of RA delaying consulting their general practitioner (GP). Previous research indicates that patients with inflammatory arthritis are likely to visit pharmacies for advice before consulting their GP. Therefore, pharmacists are well positioned to identify patients with symptoms of early inflammatory arthritis and signpost them appropriately. This research examines community pharmacy staff's knowledge, perceptions, and approaches to management of patients presenting with symptoms of RA in order to identify training needs and other opportunities for intervention to enhance the role of pharmacy staff in the pathway to care., Methods: Semi-structured interviews were conducted with 19 community pharmacy staff in the West Midlands (UK), during a 12-month period (2017-2018). The interviews were audio-recorded, transcribed, and analyzed using thematic analysis facilitated by NVivo 12., Results: There was considerable variation in knowledge and perceptions of RA and the need for early treatment amongst pharmacists and other pharmacy staff. The potential role of pharmacists and other pharmacy staff in reducing delay in help-seeking was also discussed. Four themes emerged from thematic analysis: (1) Variations in perceptions and knowledge about RA. (2) The role of the pharmacy in increasing public awareness about RA. (3) The role of the pharmacy staff in facilitating access to the GP. (4) Practical considerations for pharmacy-based interventions., Conclusion: Variability in knowledge and perceptions of RA amongst pharmacists, and amongst other pharmacy staff will affect effective signposting of suspected RA cases. This study identifies opportunities for enhanced training of community pharmacists and other pharmacy staff in relation to inflammatory arthritis as well as other pharmacy-based interventions, such as public awareness campaigns about RA and other musculoskeletal conditions. Together with existing referral services and other pharmacy-based initiatives this could result in enhanced signposting to GP consultation or other appropriate NHS services for inflammatory symptoms and reduced treatment delay., (© 2022. The Author(s).)

Objectives: There is increasing interest in prediction and prevention of RA. It is important to understand the views of those at risk to inform the development of effective approaches. First-degree relatives (FDRs) of RA patients are at increased risk of RA. This study assessed predictors of their interest in predictive testing for RA., Methods: Questionnaires were completed by RA patients (provided with their questionnaire by a healthcare professional) and their FDRs (provided with their questionnaire by their RA proband). FDR surveys assessed interest in taking a predictive test, demographic variables, perceived RA risk, attitudes about predictive testing, autonomy preferences, illness perceptions, avoidance coping and health anxiety. Patient surveys included demographic variables, disease impact, RA duration and treatment. Ordinal logistic regression examined the association between FDRs' characteristics and their interest in predictive testing. Generalized estimating equations assessed associations between patient characteristics and FDRs' interest in predictive testing., Results: Three hundred and ninety-six FDRs responded. Paired data from the RA proband were available for 292. The proportion of FDRs interested in predictive testing was 91.3%. Information-seeking preferences, beliefs that predictive testing can increase empowerment over health and positive attitudes about risk knowledge were associated with increased interest. Beliefs that predictive testing could cause psychological harm predicted lower interest. Patient characteristics of the proband were not associated with FDRs' interest., Conclusions: FDRs' interest in predictive testing for RA was high, and factors associated with interest were identified. These findings will inform the development of predictive strategies and informational resources for those at risk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

There has been intense research focus on the biological mechanisms underlying the transition from health to disease for rheumatoid arthritis (RA) over recent years, and it is now well established that a state of autoimmunity precedes the development of symptoms for a large proportion of patients. This has led to an increased interest in the identification of at-risk groups and the potential for preventive intervention. The ability of several immunomodulatory agents to delay or prevent RA is under investigation and novel cellular therapies are in development. Preventive approaches are also being assessed in other chronic autoimmune diseases. For example, an anti-CD3 antibody has recently been shown to delay progression to type 1 diabetes in non-diabetic relatives of patients identified as being at high risk. The identification and treatment of individuals as being at risk of a disease where there is a degree of uncertainty around the potential for benefit is socially and ethically challenging. Recently reported difficulties in recruitment to RA prevention trials have underlined the importance of understanding the perspectives of at-risk individuals to identify barriers and facilitators that need to be addressed in order for preventive strategies to be acceptable. Understanding of their preferences for benefits and risks of preventive interventions can inform efficient intervention prioritization, prevention trial design and the development of informational resources for those at risk. In this review we summarize current knowledge of preferences for RA prevention and make recommendations for further research needed to ensure efficient development of preventive therapies and clinical implementation., Competing Interests: KR declares personal fees from Abbvie, Sanofi, and grant/research support from Bristol Myers Squibb. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Falahee and Raza.)

Background: There is increasing research focus on prediction and prevention of rheumatoid arthritis (RA). Information about risk of RA is increasingly available via direct-to-consumer testing. However, there is limited understanding of public perceptions around predictive testing for RA. This study explores public perceptions of predictive testing for RA in comparison to breast cancer (BC) and early-onset Alzheimer's disease (AD)., Methods: Four focus groups with 21 members of the public were conducted using hypothetical vignettes about predictive testing for each disease. Transcripts of focus group proceedings were analysed inductively using thematic analysis., Results: Thematic analysis of the data produced three key themes: decision-making factors, consequences, and consumer needs. Factors suggested that might influence decision-making about predictive testing included family history, fear, and perceived severity and treatability of the illness. RA was perceived to be less severe and more treatable than BC/AD. Potential consequences of predictive testing across all diseases included lifestyle modification, planning for the future and discrimination by employers or insurers. Predictive testing for RA was perceived to have less potential for negative psychological consequences than other diseases. Participants highlighted that individuals undertaking predictive testing should be signposted to appropriate support services and receive information on the accuracy of predictive testing. It was suggested that strategies to mitigate concerns regarding communication and confidentiality of risk results are required., Conclusions: The findings of this study reflect public misunderstandings regarding RA that may impact the uptake of and responses to predictive testing, and key informational needs of individuals considering a predictive test. Predictive strategies should be accompanied by awareness-raising initiatives and informational resources., (© 2022. The Author(s).)

Treatments used for rheumatoid arthritis (RA) are under investigation for their efficacy to prevent RA in at risk groups. It is therefore important to understand treatment preferences of those at risk. We systematically reviewed quantitative preference studies of drugs to treat, or prevent RA, to inform the design of further studies and trials of RA prevention. Stated preference studies for RA treatment or prevention were identified through a search of five databases. Study characteristics and results were extracted, and the relative importance of different types of treatment attributes was compared across populations. Twenty three studies were included 20 of RA treatments (18 of patients; 2 of the general public) and 3 prevention studies with first-degree relatives (FDRs). Benefits, risks, administration method and cost (when included) were important determinants of treatment choice. A benefit was more important than a risk attribute in half of the studies of RA treatment that included a benefit attribute and 2/3 studies of RA prevention. There was variability in the relative importance of attributes across the few prevention studies. In studies with non-patient participants, attributes describing confidence in treatment effectiveness/safety were more important determinants of choice than in studies with patients. Most preference studies relating to RA are of treatments for established RA. Few studies examine preferences for treatments to prevent RA. Given intense research focus on RA prevention, additional preference studies in this context are needed. Variation in treatment preferences across different populations is not well understood and direct comparisons are needed., (© 2022. The Author(s).)

Objectives: There is increasing interest in identifying individuals at-risk of rheumatoid arthritis (RA) and initiating early treatment to prevent or delay the onset of arthritis. We aimed to describe the perceptions and experiences of at-risk individuals and to inform the conduct of clinical trials and studies, and clinical practice., Methods: A systematic review and thematic synthesis of qualitative studies was conducted. Two review authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist and assessed confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative Research approach., Results: Seven studies involving 115 individuals at-risk of developing RA were included. Three major themes (seven subthemes) were identified: understanding the risk of developing RA (knowledge of RA and identification of potential risk factors); preventive interventions to reduce the risk of developing RA (understanding the value and role of preventive interventions, and engagement with preventive interventions); and perceptions of predictive testing for RA (benefits of predictive testing, decision to undertake predictive testing and concerns about predictive testing). Moderate confidence in most review findings was evident., Conclusion: While there are clear benefits in informing individuals at-risk of RA about their risk following predictive testing and offering preventive treatment, there are potential barriers to engagement, intensified by the burden of uncertainty. Identification of the optimum approaches for presenting risk information, including the risks and benefits of engaging with preventive interventions, is urgently needed to support individuals at-risk of RA in their decision making., Prospero Registration Number: CRD42021236034., Competing Interests: Competing interests: Professor DA is an ARD Board Member., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Illness perceptions are associated with attitudes towards preventive behaviors and are therefore crucial to consider in the context of prevention of cardiovascular diseases. We investigated illness perceptions of the public about myocardial infarction, and whether they predict public preferences for health check test results. A randomly selected sample (N = 423) of the Swedish public aged 40-70 completed an online-survey. It included the brief illness perception questionnaire, items assessing sociodemographic, lifestyle and health factors and a discrete choice experiment incorporating six attributes of health checks (written results, notification method, consultation time, waiting time, lifestyle recommendation and cost). Associations between illness perceptions and sociodemographic- and cardiovascular risk factors were analyzed using multivariate linear regression. Preference data were analyzed with a mixed multinomial logit model. Presence of smoking, hypertension, obesity and lack of physical activity were associated with weaker causal beliefs for the relevant risk factor, while presence of a high stress level was associated with stronger causal beliefs for stress. Low control predicted unwillingness to receive lifestyle recommendations. Attributing family history as the most important personal cause of MI predicted unwillingness to participate in health checks. Illness perceptions differed due to presence of risk factors, age, sex and health literacy. Furthermore, illness perceptions influenced preferences for health check test results and willingness to participate in health checks. Illness perceptions should therefore be addressed when designing health communication and preventive interventions such as health checks, and methods for promoting accurate illness perceptions should be developed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2022 The Authors.)

Objectives: To identify the association between periodontal diseases (gingivitis and periodontitis) and chronic diseases including cardiovascular disease, cardiometabolic disease, autoimmune disease and mental ill health., Design: Retrospective cohort., Setting: IQVIA Medical Research Data-UK between 1 January 1995 and 1 January 2019., Participants: 64 379 adult patients with a general practitioner recorded diagnosis of periodontal disease (exposed patients) were matched to 251 161 unexposed patients by age, sex, deprivation and registration date., Main Outcome Measures: Logistic regression models accounting for covariates of clinical importance were undertaken to estimate the adjusted OR (aOR) of having chronic diseases at baseline in the exposed compared with the unexposed group. Incidence rates for each outcome of interest were then provided followed by the calculation of adjusted HRs using cox regression modelling to describe the risk of outcome development in each group., Results: The average age at cohort entry was 45 years and the median follow-up was 3.4 years. At study entry, the exposed cohort had an increased likelihood of having a diagnosis of cardiovascular disease (aOR 1.43; 95% CI 1.38 to 1.48), cardiometabolic disease (aOR 1.16; 95% CI 1.13 to 1.19), autoimmune disease (aOR 1.33; 95% CI 1.28 to 1.37) and mental ill health (aOR 1.79; 95% CI 1.75 to 1.83) compared with the unexposed group. During the follow-up of individuals without pre-existing outcomes of interest, the exposed group had an increased risk of developing cardiovascular disease (HR 1.18; 95% CI 1.13 to 1.23), cardiometabolic disease (HR 1.07; 95% CI 1.03 to 1.10), autoimmune disease (HR 1.33; 95% CI 1.26 to 1.40) and mental ill health (HR 1.37; 95% CI 1.33 to 1.42) compared with the unexposed group., Conclusions: In this cohort, periodontal diseases appeared to be associated with an increased risk of developing cardiovascular, cardiometabolic, autoimmune diseases and mental ill health. Periodontal diseases are very common; therefore, an increased risk of other chronic diseases represent a substantial public health burden., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare the incident risk of RA in patients with type 2 diabetes mellitus (T2DM) and to explore the role of glycaemic control and associated therapeutic use in the onset of RA., Methods: This study was a retrospective cohort study using patients derived from the IQVIA Medical Research Data (IMRD-UK) database between 1995 and 2019. A total of 224 551 newly diagnosed patients with T2DM were matched to 449 101 patients without T2DM and followed up to assess their risk of RA. Further analyses investigated the effect of glycaemic control, statin use and anti-diabetic drugs on the relationship between T2DM and RA using a time-dependent Cox regression model., Results: During the study period, the incidence of RA was 8.1 and 10.6 per 10 000 person-years in the exposed and unexposed groups, respectively. The adjusted hazard ratio (aHR) was 0.73 (95% CI 0.67, 0.79). In patients who had not used statins in their lifetime, the aHR was 0.89 (95% CI 0.69, 1.14). When quantifying the effects of glycaemic control, anti-diabetic drugs and statins using time-varying analyses, there was no association with glycaemic control [aHR 1.00 (95% CI 0.99, 1.00)], use of metformin [aHR 1.00 (95% CI 0.82, 1.22)], dipeptidyl peptidase-4 inhibitors [DPP4is; aHR 0.94 (95% CI 0.71, 1.24)] and the development of RA. However, statins demonstrated a protective effect for progression of RA in those with T2DM [aHR 0.76 (95% CI 0.66, 0.88)], with evidence of a duration-response relationship., Conclusion: There is a reduced risk of RA in patients with T2DM that may be attributable to the use of statins., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: There is an increased interest in patient preferences informing the development and authorisation of medical products. A requirement for robust and meaningful results of such studies is that patients adequately understand the risks and benefits associated with treatments for which their preferences are elicited. This study aims to determine the influence of an educational tool, compared with traditional written information on patient preferences elicited in a discrete choice experiment (DCE)., Methods: Treatment preferences of Swedish patients with rheumatoid arthritis (RA) were assessed using a DCE. Patients were recruited via clinics, a research panel, and the Swedish Rheumatism Association. Respondents received training materials either as plain written text or as an online educational tool. The educational tool was designed to enhance understanding of the written text by using graphics, pictograms, icon arrays, spoken text, and click-on functions. Data were analysed using random parameter logit models., Results: 675 patients with RA were included in the analysis. The patients received either a written information (n = 358) or information via an educational tool (n = 317). Respondents receiving the educational tool placed relatively more importance on all included side effects in their decision making, compared to respondents receiving the written text, who placed greater importance on treatment effectiveness and administration methods., Conclusion: Compared to the respondents receiving the written text, the decisions of respondents receiving the educational tool were more influenced by medication side effects. Further research is needed to provide guidance on how and when to use educational tools to inform and elicit patients' preferences., Practice Implications: The ways in which attributes are presented to patients significantly impacts preferences measured in a DCE., Competing Interests: Conflict of interest KSB, JV, MH, EB, MF and UK have no conflict of interest to declare. KR is supported by the Birmingham NIHR Biomedical Research Centre and is a member of the Research into Inflammatory Arthritis Centre Versus Arthritis and the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Patient preferences are gaining recognition among key stakeholders involved in benefit-risk decision-making along the medical product lifecycle. However, one of the main challenges of integrating patient preferences in benefit-risk decision-making is understanding differences in patient preference, which may be attributable to clinical characteristics (eg age, medical history) or psychosocial factors. Measuring the latter may provide valuable information to decision-makers but there is limited guidance regarding which psychological dimensions may influence patient preferences and which psychological instruments should be considered for inclusion in patient preference studies. This paper aims to provide such guidance by advancing evidence and consensus-based recommendations and considerations. Findings of a recent systematic review on psychological constructs having an impact on patients' preferences and health-related decisions were expanded with input from an expert group (n = 11). These data were then used as the basis for final recommendations developed through two rounds of formal evaluation via an online Delphi consensus process involving international experts in the field of psychology, medical decision-making, and risk communication (n = 27). Three classes of recommendations emerged. Eleven psychological constructs reached consensus to be recommended for inclusion with the strongest consensus existing for health literacy, numeracy, illness perception and treatment-related beliefs. We also proposed a set of descriptive and checklist criteria to appraise available psychological measures to assist researchers and other stakeholders in including psychological assessment when planning patient preference studies. These recommendations can guide researchers and other stakeholders when designing and interpreting patient preference studies with a potential high impact in clinical practice and medical product benefit-risk decision-making processes., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Russo et al.)

Introduction: Amidst growing consensus that stakeholder decision-making during drug development should be informed by an understanding of patient preferences, the Innovative Medicines Initiative project 'Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle' (PREFER) is developing evidence-based recommendations about how and when patient preferences should be integrated into the drug life cycle. This protocol describes a PREFER clinical case study which compares two preference elicitation methodologies across several populations and provides information about benefit-risk trade-offs by those at risk of rheumatoid arthritis (RA) for preventive interventions., Methods and Analysis: This mixed methods study will be conducted in three countries (UK, Germany, Romania) to assess preferences of (1) first-degree relatives (FDRs) of patients with RA and (2) members of the public. Focus groups using nominal group techniques (UK) and ranking surveys (Germany and Romania) will identify and rank key treatment attributes. Focus group transcripts will be analysed thematically using the framework method and average rank orders calculated. These results will inform the treatment attributes to be assessed in a survey including a discrete choice experiment (DCE) and a probabilistic threshold technique (PTT). The survey will also include measures of sociodemographic variables, health literacy, numeracy, illness perceptions and beliefs about medicines. The survey will be administered to (1) 400 FDRs of patients with RA (UK); (2) 100 FDRs of patients with RA (Germany); and (3) 1000 members of the public in each of UK, Germany and Romania. Logit-based approaches will be used to analyse the DCE and imputation and interval regression for the PTT., Ethics and Dissemination: This study has been approved by the London-Hampstead Research Ethics Committee (19/LO/0407) and the Ethics Committee of the Friedrich-Alexander-Universität Erlangen-Nürnberg (92&#95;17 B). The protocol has been approved by the PREFER expert review board. The results will be disseminated widely and will inform the PREFER recommendations., Competing Interests: Competing interests: MF, GS, LVM, ME, KB, UK, BH and JV have no competing interests to declare. RLD is employed by Janssen Pharmaceuticals and is a shareholder of Johnson & Johnson. CR is an employee and shareholder of Eli Lilly and Company. ST-L is employed by Sanofi R&D and is a shareholder of Sanofi. KR reports grants and personal fees from AbbVie, grants and personal fees from Pfizer, personal fees from Sanofi, personal fees from Lilly, personal fees from Bristol Myers Squibb, personal fees from UCB, personal fees from Janssen, and personal fees from Roche Chugai, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Preference assessments of patients with rheumatoid arthritis can support clinical therapeutic decisions for including biologic and targeted synthetic medicines to use. This study assesses patient preferences for attributes of second-line therapies and heterogeneity within these preferences to estimate the relative importance of treatment characteristics and to calculate the minimum benefit levels patients require to accept higher levels of side effects., Methods: Between November 2018 to August 2019, patients with rheumatoid arthritis were recruited to a survey containing demographic and disease-related questions as well as a discrete choice experiment to measure their preferences for second-line therapies using biologics or Janus kinases inhibitors. Treatment characteristics included were route of administration, frequency of use, probability of mild short-term side effects, probability of side effects changing appearance, probability of psychological side effects, probability of severe side effects and effectiveness of treatment., Results: A total of 358 patients were included in the analysis. A latent class analysis revealed three preference patterns: (1) treatment effectiveness as the single most important attribute, (2) route of administration as the most important attribute, closely followed by frequency of use and psychological side effects and (3) severe side effects as the most important attribute followed by psychological side effects. In addition, disease duration and mild side effects influenced the patients' choices., Conclusion: Respondents found either effectiveness, route of administration or severe side effects as the most important attribute. Patients noting effectiveness as most important were more willing than other patients to accept higher risks of side effects.

Objective: Little is known about the experiences, values, and needs of people without arthritis who undergo predictive biomarker testing for the development of rheumatoid arthritis (RA). Our study aimed to explore the perspectives of these individuals and describe their information needs., Methods: A qualitative, multicenter interview study with a thematic analysis was conducted in Austria, Germany and the UK. Individuals were interviewed who underwent predictive biomarker testing for RA and had a positive test result but no diagnosis of any inflammatory joint disease. Participants included patients with arthralgia and asymptomatic individuals. Information and education needs were developed from the qualitative codes and themes using the Arthritis Educational Needs Assessment Tool as a frame of reference., Results: Thematic saturation was reached in 34 individuals (76% female, 24 [71%] with arthralgia, and 10 [29%] asymptomatic individuals). Thirty-seven codes were summarized into 4 themes: 1) decision-making around whether to undergo initial predictive testing, 2) willingness to consider further predictive tests, and/or 3) preventive interventions, including medication, and 4) varying reactions after receiving a positive test result. Individuals with arthralgia were more likely to be willing to take preventive action, undergo further testing, and experience psychological distress than asymptomatic individuals. All participants expressed the need for tailored, patient-understandable information., Conclusion: Individuals at risk of RA are currently the subjects of research aimed at developing better predictive strategies and preventive approaches. Their perceptions and needs should be addressed to inform the future development of interventions combined with education., (© 2019 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Plain English Summary: Patient and public involvement (PPI) improves the quality of health research and ensures that research is relevant to patients' needs. Though PPI is increasingly evident in clinical and health services research, there are few examples in the research literature of effective PPI in translational and laboratory-based research. In this paper, we describe the development and evaluation of PPI in a multi-centre European project (EuroTEAM - T owards E arly biomarkers in A rthritis M anagement) that included both translational and laboratory-based and psychosocial research. We found that although most PPI in EuroTEAM was centred around the psychosocial research, there were examples of PPI in the laboratory studies. As the project evolved, researchers became better at accommodating PPI and identifying PPI opportunities. It was generally agreed that PPI had a positive impact on the project overall, particularly on public engagement with the research. We concluded that the inclusion of both psychosocial and laboratory-based research in the same project facilitated PPI across all aspects of the research. In future projects, we would try to specify individual PPI activities in more detail at the project-planning stage, and better accommodate patient partners who are not native speakers of English., Abstract: Background Patient and public involvement (PPI) enhances research quality and relevance and is central to contemporary health policy. The value of PPI has been recognised in rheumatology research, though there are limited examples of PPI in basic and translational science. The EU FP7 funded 'EuroTEAM' ( T owards E arly biomarkers in A rthritis M anagement) project was established to develop biomarker-based approaches to predict the future development of rheumatoid arthritis and incorporated psychosocial research to investigate the perceptions of 'at risk' individuals about predictive testing, and to develop informational resources about rheumatoid arthritis (RA) risk. Patient involvement was central to EuroTEAM from the inception of the project. The objective of this paper is to describe the development of PPI in EuroTEAM, formatively assess the impact of PPI from the perspectives of researchers and patient research partners (PRPs), reflect on successes and lessons learned, and formulate recommendations to guide future projects. Methods Two mixed-methods surveys (for PRPs and researchers) and a teleconference were undertaken to assess the impact of PPI on individual work packages and on EuroTEAM overall. Results There was consensus about the positive impact of PPI on the research and on the experiences of those involved. In particular, the positive impact of PPI on the personal development of researchers, and on effective public engagement with EuroTEAM research were highlighted. Researchers described adapting their practice in future projects to facilitate PPI. Spin-off projects and ongoing collaborations between PRPs and researchers reflected the value of PPI to participants. PPI was more frequently integrated in psychosocial research, though examples of PPI in laboratory/translational science were also described. PRPs asked for more opportunities to contribute meaningfully to basic scientific research and for more extensive feedback on their contributions. Conclusions The findings were used to formulate recommendations to guide effective involvement of patients in future similar projects, including identifying specific training requirements for PRPs and researchers, the identification of PRP focused tasks/deliverables at the project planning stage, and supporting access to involvement for all PRPs. Importantly, the distinctive multidisciplinary approach of EuroTEAM, incorporating both basic science and psychosocial research, facilitated patient involvement in the project overall., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Effective treatments for rheumatoid arthritis (RA) are available and can lead to remission for some patients, but most patients remain on potentially toxic and expensive medications in the long term. Interest is increasingly turning to the disease phases preceding the development of RA that represent opportunities for preventive interventions. At-risk target populations include individuals with genetic and environmental risk factors, those who have developed systemic autoimmunity, and those who have developed clinically suspect symptoms (eg, arthralgias without synovitis, or an early arthritis). Ongoing prospective studies will inform the development of increasingly accurate predictive tools to identify individuals at risk of developing RA. Furthermore, a range of preventive approaches has been suggested, including lifestyle modification (eg, smoking cessation) and pharmacologic interventions (eg, hydroxychloroquine, methotrexate, abatacept, rituximab) that are currently the subject of randomized controlled trials. As prediction and prevention of RA evolve, it is increasingly likely that individuals at risk (including asymptomatic individuals) may be faced with complex decisions about whether to accept assessment of their risk status or to take a preventive intervention associated with risk of serious adverse events and uncertain benefit. Acceptance of preventive medication in other contexts can be low. For example, <25% of women at high risk of breast cancer are willing to take preventive hormonal treatments. Actual uptake is lower still. Patients' beliefs and preferences predict treatment uptake and adherence. Before the dream of preventing RA can become reality, health care providers need to understand the perspectives of individuals in the target population and to identify barriers and facilitators for this approach. This commentary reviews what is currently known about the perspectives of patients and individuals at risk about predictive and preventive approaches for RA and identifies gaps to be addressed to inform the development of efficient preventive strategies., (Copyright © 2019. Published by Elsevier Inc.)

Background: Research has been mainly focused on how to elicit patient preferences, with less attention on why patients form certain preferences., Objectives: To assess which psychological instruments are currently used and which psychological constructs are known to have an impact on patients' preferences and health-related decisions including the formation of preferences and preference heterogeneity., Methods: A systematic database search was undertaken to identify relevant studies. From the selected studies, the following information was extracted: study objectives, study population, design, psychological dimensions investigated, and instruments used to measure psychological variables., Results: Thirty-three studies were identified that described the association between a psychological construct, measured using a validated instrument, and patients' preferences or health-related decisions. We identified 33 psychological instruments and 18 constructs, and categorized the instruments into 5 groups, namely, motivational factors, cognitive factors, individual differences, emotion and mood, and health beliefs., Conclusions: This review provides an overview of the psychological factors and related instruments in the context of patients' preferences and decisions in healthcare settings. Our results indicate that measures of health literacy, numeracy, and locus of control have an impact on health-related preferences and decisions. Within the category of constructs that could explain preference and decision heterogeneity, health locus of control is a strong predictor of decisions in several healthcare contexts and is useful to consider when designing a patient preference study. Future research should continue to explore the association of psychological constructs with preference formation and heterogeneity to build on these initial recommendations., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: There is increasing interest in the identification of people at risk of rheumatoid arthritis (RA) to monitor the emergence of early symptoms (and thus allow early therapy), offer lifestyle advice to reduce the impact of environmental risk factors and potentially offer preventive pharmacological treatment for those at high risk. Close biological relatives of people with RA are at an increased risk of developing RA and are therefore potential candidates for research studies, screening initiatives and preventive interventions. To ensure the success of approaches of this kind, a greater understanding of the perceptions of this group relating to preventive measures is needed., Methods: Twenty-four first-degree relatives of patients with an existing diagnosis of RA from the UK, three from Germany and seven from Austria (age: 21-67 years) took part in semi-structured interviews exploring their perceptions of RA risk, preventive medicine and lifestyle changes to reduce RA risk. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis., Results: Many first-degree relatives indicated that they anticipated being happy to make lifestyle changes such as losing weight or changing their diet to modify their risk of developing RA. Participants further indicated that in order to make any lifestyle changes it would be useful to know their personal risk of developing RA. Others implied they would not contemplate making lifestyle changes, including stopping smoking, unless this would significantly reduce or eliminate their risk of developing RA. Many first-degree relatives had more negative perceptions about taking preventive medication to reduce their risk of RA, and listed concerns about potential side effects as one of the reasons for not wanting to take preventive medicines. Others would be more willing to consider drug interventions although some indicated that they would wish to wait until symptoms developed., Conclusions: Information targeted at those considered to be at risk of RA should contain information about RA, the extent to which risk can be quantified at an individual level and how risk levels may differ depending on whether early symptoms are present. The benefits (and risks) of lifestyle changes and pharmacological interventions as potential preventive measures should be clearly described., Competing Interests: Ethical approval was obtained from the Humber Bridge National Research Ethics Committee (UK), from the Ethics Committee of the Medical University of Vienna (Austria) and from the Ethics Committee of the University of Erlangen-Nuremberg (Germany). All participants gave their written informed consent.We have received written informed consent from all our interviewees to publish the details, including the anonymised quotes from the interviews, contained within this manuscript.Rebecca Jayne Stack is an editorial board member for this journal. All other authors declare they have no conflicts of interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.