Facilitating personal development for public involvement in health‐care education and research: A co‐produced pilot study in one UK higher education institute

BackgroundPublic involvement in the education of students enrolled on higher education programmes has gained impetus. For students enrolled on professional health‐care programmes and health‐related modules in the UK, there is also a requirement by professional bodies to include “service user” involvement in preparation for entry to a professional health‐care register and continuing professional development. Actively involving patients and members of the public in research is also a requirement by many research funders. In this article, the term Patient and Public Involvement (PPI) will be used throughout to include lay members, volunteers, user and carers.ObjectivesA unique pilot study was introduced across a health faculty to integrate PPI in a deliberate way. It aimed to provide an educational, focused programme of events that was meaningful to develop and inform peoples’ knowledge, skills and confidence for their involvement in the health faculty.DesignPPI members volunteered to sit on a steering group to determine the educational journey; the outcomes of three focus groups with PPI members (N = 32) and academics informed the programme content which included a range of workshops covering the exploration of public roles and barriers to involvement, introduction to research and interviewing skills.ResultsThe workshops were well attended, and outcomes indicated the importance of co‐production when designing, delivering and evaluating programmes.DiscussionCo‐production underpinned this pilot study, resulting in a programme which was meaningfully received by public contributors.RecommendationsCo‐production was seen as integral to this research to ensure that outcomes were indeed “fit for purpose”.     

Mitigating unintended consequences of co‐design in health care

BackgroundCo‐design and associated terms are increasingly being used to facilitate values‐based approaches to health‐care improvement. It is messy and complex, involving diverse actors.MethodsWe explore the notion that initiatives have outcomes other than initially planned is neither new nor novel but is overlooked when thinking about co‐design. We explore some of the unintended consequences and outline some optimal conditions that can mitigate challenges.DiscussionAlthough co‐design approaches are being applied in health care, questions remain regarding its ability to produce gains in health outcomes. Little is known about determining whether co‐design is the most suitable approach to achieve the given project goals, the levels of involvement required to realize the benefits of co‐design or the potential unintended consequences. There is a risk of further marginalizing or adding burden to under‐represented populations and/or over‐researched populations.ConclusionUndertaking a co‐design approach without the optimal conditions for inclusive involvement by all may not result in an equal partnership or improve health or care quality outcomes. Co‐design requires on‐going reflective discussions and deliberative thinking to remove any power imbalances. However, without adequate resources, a focus on implementation and support from senior leaders, it is a tough ask to achieve.Patient or Public ContributionThis viewpoint article was written by two academics who have undertaken a significant amount of PPI and co‐design work with members of the public and patient''s right across the health system. Our work guided the focus of this viewpoint as we reflected on our experiences.     

Adapting patient and public involvement in patient‐oriented methods research: Reflections in a Canadian setting during COVID‐19

BackgroundProcesses of the patient and public involvement (PPI) in health research shifted quickly during 2020. Faced with large‐scale issues, such as the COVID‐19 pandemic, the need to adapt processes of PPI to uphold commitments to nurturing the practice of ‘nothing about us without us’ in research has been urgent and profound. We describe how processes of PPI in research on patient‐oriented methods of knowledge translation and implementation science were adapted by four teams in a Canadian setting.MethodsAs part of an ongoing quality improvement self‐study to enhance PPI within these teams, team members shared their experiences of PPI in the context of this pivotal year during interviews and facilitated discussions. Drawing on these experiences, we outline challenges and reflections for adapting processes of PPI in health research on methods in times of urgency, conflict and fast‐moving change.DiscussionOur reflections offer insight into common issues encountered across teams that may be amplified during times of rapid change, including handling change and uncertainty, sustaining relationship‐building and hearing differing perspectives in processes of PPI.ConclusionThese learnings present an opportunity to help others active in or planning patient‐oriented methods research to reflect on the changing nature of PPI and how to adapt PPI processes in response to turbulent situations in the future.     

Knowledge sharing to support long‐term condition self‐management—Patient and health‐care professional perspectives

BackgroundIncreased self‐management is a suggested solution to the burden on health‐care services of long‐term conditions (LTCs). This requires effective sharing of knowledge between health‐care professionals and patients, and is an underexplored area.ObjectiveTo understand how patients and health‐care professionals (HCPs) share and utilize knowledge in the social context of health‐care interactions within long‐term condition management.MethodsThematic analysis of 93 hours of observations of health‐care interactions and 33 semi‐structured interviews involving patients, carers and HCPs.Results3 themes were identified: normative social roles, differing professional roles and the value of knowledge. Knowledge sharing was a complex process heavily influenced by social and cultural norms within the health‐care context. Not all knowledge was easily shared within routine health‐care interactions.DiscussionThe social context in which health‐care is practised influences what knowledge is shared and how this is achieved. It favours sharing of clinical knowledge from HCPs to patients and disadvantages patients in their ability to share their unique knowledge based on lived experience of illness. The opportunities for patients to be supported in their knowledge, skills and confidence within routine health‐care interactions are limited.ConclusionBoth patients and HCPs need support to recognize the characteristics of the social context of health care and their understandings of their roles within this in order for them to move beyond accepted behaviours to develop more effective partnership working.Patient or Public ContributionPatients were involved in initial design of the study, particularly ethics of ethnographic observation.     

Shared decision‐making in standardized cancer patient pathways in Norway—Narratives of patient experiences

BackgroundCancer patient pathways (CPPs) were implemented in Norway in 2015–2017 to advance cancer diagnostics and treatment initiation. The aim of CPPs is to ensure standardized waiting times, but also to strengthen patient participation and shared decision‐making. This study investigates how patients enrolled in a CPP experienced shared decision‐making.MethodsThis study comprised of 19 individual semistructured interviews with patients who had been enrolled in a CPP at three hospitals in Norway. Twelve patients had breast cancer, four patients had prostate cancer and three patients had malignant melanoma. We analyzed their experiences using a narrative approach.FindingsThis study showed how participating in a standardized CPP provided different possibilities for shared decision‐making. The patients'' narratives of shared decision‐making in CPPs included stories from the three cancer diagnoses through the following themes: (1) The predictable safeness of standardizations, (2) the ambivalence of making decisions and (3) opposing standardizations and pushing for action.ConclusionStandardized CPPs provided patients with predictability and safety. Shared decision‐making was possible when the cancer diagnoses supported preference‐sensitive treatment options. Balancing standardizations with individualized care is necessary to facilitate patient participation in CPPs, and the possibility of shared decision‐making needs to be discussed for each specific CPP.Patient or Public ContributionA service user representative from the Norwegian Cancer Society participated in designing this study.     

Information,deliberation, and decisional control preferences for participation in medical decision‐making and its influencing factors among Chinese cancer patients

BackgroundPatient‐centred care should strive to respond to the individual patient''s needs and preferences when possible. Yet, preferences of cancer patients for participation in different stages of the medical decision‐making process to increase matching of preferred and actual participation of the patients in decision‐making are not well known.ObjectiveThis study aimed to determine the level of information, deliberation and decisional control preferences in decision‐making practices among Chinese cancer patients and to explore their association with the sociodemographic and clinical variables of the patients.MethodsA cross‐sectional study was conducted involving a convenience sample of 328 cancer patients from three public hospitals in Guangzhou, China. The Patient Expectation for Participation in Medical Decision‐making Scale (PEPMDS) was used to evaluate information, deliberation and decisional control preferences of the patients. Binary logistic regressions were conducted to determine the association between sociodemographic variables, clinical variables and preferences of the patients.ResultsMost patients reported a high preference for information (73.2%) and deliberation (73.8%), while a small number (37.2%) reported a high preference for decisional control. Younger patients and patients with higher levels of education were significantly more likely to have a high preference for information, deliberation and decisional control. Patients with low annual family incomes were significantly more likely to have a low preference for decisional control.ConclusionPreferences of patients for involvement in different stages of decision‐making practices could vary. The level of preferences appears to be related to the patient''s age, education level, and financial status.Practice ImplicationsHealthcare providers should tailor the participatory approaches of patients considering individual preferences for information, deliberation and decisional control during medical decision‐making.Patient ContributionPatients participated in the survey and filled in the questionnaires.     

An alternate level of care plan: Co‐designing components of an intervention with patients,caregivers and providers to address delayed hospital discharge challenges

ObjectiveTo engage with patients, caregivers and care providers to co‐design components of an intervention that aims to improve delayed hospital discharge experiences.DesignThis is a qualitative study, which entailed working groups and co‐design sessions utilizing World Café and deliberative dialogue techniques to continually refine the intervention.Setting and ParticipantsOur team engaged with 61 participants (patients, caregivers and care providers) in urban and rural communities across Ontario, Canada. A 7‐member Patient and Caregiver Advisory Council participated in all stages of the research.ResultsKey challenges experienced during a delayed discharge by patients, caregivers and care providers were poor communication and a lack of care services. Participants recommended a communication guide to support on‐going conversation between care providers, patients and caregivers. The guide included key topics to cover and questions to ask during initial and on‐going conversations to manage expectations and better understand the priorities and goals of patients and caregivers. Service recommendations included getting out of bed and dressed each day, addressing the psycho‐social needs of patients through tailored activities and having a storyboard at the bedside to facilitate on‐going engagement.Discussion and ConclusionsOur findings outline ways to meaningfully engage patients and caregivers during a delayed hospital discharge. Combining this with a minimal basket of services can potentially facilitate a better care experience and outcomes for patients, their care providers and families.     

Preference‐based patient participation for most,if not all: A cross‐sectional study of patient participation amongst persons with end‐stage kidney disease

BackgroundPatient participation is considered central for good healthcare. Yet, the concept is not fully understood when it comes to patients'' experiences of participation in conjunction with their preferences, particularly in long‐term healthcare. The aim of this study was to investigate the extent and variation of preference‐based patient participation in patients with end‐stage kidney disease (ESKD).MethodsA cross‐sectional study was conducted with 346 patients in renal care. The main variables were patients'' preferences for and experiences of patient participation, determined using the Patient Preferences for Patient Participation tool, the 4Ps. Analyses identified the degree of match between preferences and experiences, that is, the preference‐based patient participation measure.ResultsOverall, 57%–84% of the patients reached a sufficient level of preference‐based patient participation on the items, while 2%–12% reached an insufficient level. A mismatch indicated either less or more participation than preferred; for example, 40% had less experience than preferred for taking part in planning, and 40% had more than preferred for managing treatment.ConclusionThis study shows that, although many patients reach a sufficient level of preference‐based patient participation, this is not the case for all patients and/or attributes. Further opportunities for a mutual understanding of patients'' preferences are needed for healthcare professionals to support person‐centred patient participation.Patient or Public ContributionThe 4Ps is manufactured in collaboration with people with experience of the patient role, and persons living with ESKD were engaged in identifying their preferences and experiences of participation in renal care.     

‘As soon as you've been there,it makes it personal’: The experience of health‐care staff shadowing patients at the end of life

BackgroundPatient shadowing is an experiential technique intended to enable those who shadow to understand care experience from the patient''s point of view. It is used in quality improvement to bring about change that focuses on what is important for patients.AimTo explore the acceptability of patient shadowing for health‐care staff, the impact of the experience and subsequent motivations to make improvements.MethodA qualitative study with a diverse sample of 20 clinical and non‐clinical health‐care staff in different end‐of‐life settings. Data were analysed thematically.ResultsAnticipated anxieties about shadowing did not materialize in participant accounts, although for some it was a deeply emotional experience, intensified by being with patients who were at the end of life. Shadowing not only impacted on participants personally, but also promoted better insights into the experience of patients, thus focusing their improvement efforts. Participants reported that patients and families who were shadowed welcomed additional caring attention.ConclusionWith the right preparation and support, patient shadowing is a technique that engages and motivates health‐care staff to improve patient‐centred care.     

The psychological burden of waiting for procedures and patient‐centred strategies that could support the mental health of wait‐listed patients and caregivers during the COVID‐19 pandemic: A scoping review

BackgroundWaiting for procedures delayed by COVID‐19 may cause anxiety and related adverse consequences.ObjectiveTo synthesize research on the mental health impact of waiting and patient‐centred mitigation strategies that could be applied in the COVID‐19 context.MethodsUsing a scoping review approach, we searched 9 databases for studies on waiting lists and mental health and reported study characteristics, impacts and intervention attributes and outcomes.ResultsWe included 51 studies that focussed on organ transplant (60.8%), surgery (21.6%) or cancer management (13.7%). Most patients and caregivers reported anxiety, depression and poor quality of life, which deteriorated with increasing wait time. The impact of waiting on mental health was greater among women and new immigrants, and those of younger age, lower socio‐economic status, or with less‐positive coping ability. Six studies evaluated educational strategies to develop coping skills: 2 reduced depression (2 did not), 1 reduced anxiety (2 did not) and 2 improved quality of life (2 did not). In contrast, patients desired acknowledgement of concerns, peer support, and periodic communication about wait‐list position, prioritization criteria and anticipated procedure date.ConclusionsFindings revealed patient‐centred strategies to alleviate the mental health impact of waiting for procedures. Ongoing research should explore how to optimize the impact of those strategies for diverse patients and caregivers, particularly in the COVID‐19 context.Patient or Public ContributionSix patients and four caregivers waiting for COVID‐19‐delayed procedures helped to establish eligibility criteria, plan data extraction and review a draft and final report.     

Experiences of self‐care during the COVID‐19 pandemic among individuals with rheumatoid arthritis: A qualitative study

ObjectivesThis study aimed to explore the impact of the coronavirus disease 2019 (COVID‐19) pandemic on self‐care of individuals living with rheumatoid arthritis (RA).MethodsGuided by a constructivist, qualitative design, we conducted one‐to‐one in‐depth telephone interviews between March and October 2020 with participants with RA purposively sampled for maximum variation in age, sex and education, who were participating in one of two ongoing randomized‐controlled trials. An inductive, reflexive thematic analysis approach was used.ResultsTwenty‐six participants (aged 27–73 years; 23 females) in British Columbia, Canada were interviewed. We identified three themes: (1) Adapting to maintain self‐care describes how participants took measures to continue self‐care activities while preventing virus transmissions. While spending more time at home, some participants reported improved self‐care. (2) Managing emotions describes resilience‐building strategies such as keeping perspective, positive reframing and avoiding negative thoughts. Participants described both letting go and maintaining a sense of control to accommodate difficulties and emotional responses. (3) Changing communication with health professionals outlined positive experiences of remote consultations with health professionals, particularly if good relationships had been established prepandemic.ConclusionThe insights gained may inform clinicians and researchers on ways to support the self‐care strategies of individuals with RA and other chronic illnesses during and after the COVID‐19 pandemic. The findings reveal opportunities to further examine remote consultations to optimize patient engagement and care.Patient or Public ContributionThis project is jointly designed and conducted with patient partners in British Columbia, Canada. Patient partners across the United Kingdom also played in a key role in providing interpretations of themes during data analysis.     

Proposals for person‐centred care in the COVID‐19 era. Delphi study

BackgroundIn this COVID‐19 era, we need to rethink the criteria used to measure the results of person‐centred care strategies.ObjectiveTo identify priorities, and criteria that health services can use to pursue actually the goal of achieving person‐centred care.DesignThree‐phase online qualitative study performed during May–July of 2020 using the Delphi technique.Setting and ParticipantsAn online platform was used for a consensus meeting of 114 participants, including health planning experts, health‐care institution managers, clinicians and patients.Main Outcome MeasuresCriteria and indicators for the achievement of person‐centred care.Main ResultsThe first round began with 125 proposals and 11 dimensions. After the second round, 28 ideas reached a high level of consensus among the participants. Ultimately, the workgroup agreed on 20 criteria for goals in the implementation of person‐centred care during the COVID‐19 era and 21 related indicators to measure goal achievement.DiscussionNine dimensions and 28 priorities were identified. These priorities are also in accordance with the quadruple aim approach, which emphasizes the need for care for health‐care professionals, without whom it is impossible to achieve a better quality of care.ConclusionsPerson‐centred care continues to be a key objective. However, new metrics are needed to ensure its continued development during the restoration of public health services beyond the control of COVID‐19.Patient or Public ContributionTwelve professionals and patient representatives participated voluntarily in the construction of the baseline questionnaire and in the selection of the criteria and indicators using an online platform for consensus meetings.     

Patient representatives: Crucial members of health‐care working groups facing an uncertain role and conflicting expectations. A qualitative study

BackgroundPatient representatives (PRs) have been involved for decades in health‐care development, and their participation is increasingly sought in health‐care working groups (HCWGs) on every level. However, information on how the role could be further developed and teamwork improved remains sparse.ObjectiveTo explore the role of patient representatives in clinical practice guideline (CPG) monitoring groups, to describe their contributions and identify possibilities of improvement.DesignQualitative design using semi‐structured interviews analysed by content analysis.Setting and participantsInterviews were conducted with 11 PRs, 13 registered nurses, and 9 physicians, all members of national committees monitoring CPGs for cancer in Sweden.ResultsMost participants considered the PR role important but mentioned several problems. PRs’ contributions were hampered by uncertainties about their role, the low expectations of other group members and their sense that their contributions were often disregarded. Some professionals questioned whether PRs were truly representative and said some topics could not be discussed with PRs present.ConclusionThis study highlights the fundamental problems that remain to be solved despite the long involvement of PRs in HCWGs. Even though the PR role and teamwork differed between the groups, most PRs need to be empowered to be actively involved in the teamwork and have their engagement and knowledge fully utilized. Enhancing teamwork through clarifying roles and expectations could lead to more inclusive and equal teams able to work more effectively towards the goal of improving health care.Patient or public contributionPRs were information givers in data collection.     

Acceptability of risk‐stratified population screening across cancer types: Qualitative interviews with the Australian public

BackgroundThere is mounting evidence of the benefit of risk‐stratified (risk‐tailored) cancer population screening, when compared to standard approaches. However, shifting towards this approach involves changes to practice that may give rise to implementation challenges.ObjectivesTo explore the public''s potential acceptance of risk‐stratified screening across different cancer types, including reducing screening frequency if at low risk and the use of personal risk information, to inform implementation strategies.MethodSemi‐structured interviews were conducted with 40 public participants; half had received personal genomic risk information and half had not. Participants were prompted to consider different cancers. Data were analysed thematically as one dataset.ResultsThemes included the following: (a) a sense of security; (b) tailored screening is common sense; (c) risk and the need to take action; (d) not every cancer is the same; and (e) trust and belief in health messages. Both groups expressed similar views. Participants were broadly supportive of risk‐stratified screening across different cancer types, with strong support for increased screening frequency for high‐risk groups. They were less supportive of reduced screening frequency or no screening for low‐risk groups. Findings suggest the public will be amenable to reducing screening when the test is invasive and uncomfortable; be less opposed to forgo screening if offered the opportunity to screen at some stage; and view visible cancers such as melanoma differently.ConclusionsApproaching distinct cancer types differently, tailoring messages for different audiences and understanding reasons for participating in screening may assist with designing future implementation strategies for risk‐stratified cancer screening.     

Assessing and promoting partnership between patients and health‐care professionals: Co‐construction of the CADICEE tool for patients and their relatives

ContextPartnership between patients and health‐care professionals (HCPs) is a concept that needs a valid, practical measure to facilitate its use by patients and HCPs.ObjectiveTo co‐construct a tool for measuring the degree of partnership between patients and HCPs.DesignThe CADICEE tool was developed in four steps: (1) generate key dimensions of patient partnership in clinical care; (2) co‐construct the tool; (3) assess face and content validity from patients’ and HCPs’ viewpoints; and (4) assess the usability of the tool and explore its measurement performance.ResultsThe CADICEE tool comprises 24 items under 7 dimensions: 1) relationship of Confidence or trust between the patient and the HCPs; 2) patient Autonomy; 3) patient participation in Decisions related to care; 4) shared Information on patient health status or care; 5) patient personal Context; 6) Empathy; and 7) recognition of Expertise.Assessment of the tool''s usability and measurement performance showed, in a convenience sample of 246 patients and relatives, high face validity, acceptability and relevance for both patients and HCPs, as well as good construct validity.ConclusionsThe CADICEE tool is developed in co‐construction with patients to evaluate the degree of partnership in care desired by patients in their relationship with HCPs. The tool can be used in various clinical contexts and in different health‐care settings.Patient or Public ContributionPatients were involved in determining the importance of constructing this questionnaire. They co‐constructed it, pre‐tested it and were part of the entire questionnaire development process. Three patients participated in the writing of the article.     

Validation analysis of a composite real‐world mortality endpoint for patients with cancer in the United States

ObjectiveWe expanded the previous assessment of a mortality variable suited for real‐world evidence‐focused oncology research.Data sourceWe used a nationwide electronic health record (EHR)‐derived de‐identified database.Data collectionWe included patients with at least 1 of 18 cancer types between January 1, 2011 and December 31, 2017. Patient‐level structured data (EHRs, obituaries, and Social Security Death Index) and unstructured EHR data (abstracted) were linked to generate a composite mortality variable.Study designWe benchmarked sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ±15‐day agreement against the National Death Index (NDI). Real‐world overall survival (rwOS) was estimated using the Kaplan‐Meier method. We performed sensitivity analyses using a smaller patient cohort that underwent next‐generation sequencing testing.Principal findingsCompared with the NDI across 18 cancer types (overall N = 160 436): sensitivity, 83.9%‐91.5% (17/18 cancer types had sensitivity ≥85.0%); specificity, 93.5%‐99.7%; PPV, 96.3%‐98.3%; NPV, 75.0%‐98.7%; ±15‐day agreement, 95.6%‐97.6%; and median rwOS estimates ranging from 2.8% to 12.7% greater. Sensitivity analysis results (n = 17 540) were consistent with the main analysis.ConclusionsAcross all cancer types analyzed, this composite mortality variable showed high sensitivity, specificity, PPV, NPV, and ±15‐day agreement, and yielded median rwOS values modestly overestimated when compared to NDI‐based results.     

Interactional practices in person‐centred care: Conversation analysis of nurse‐patient disagreement during self‐management support

BackgroundPerson‐centred care implies a change in interaction between care professionals and patients where patients are not passive recipients but co‐producers of care. The interactional practices of person‐centred care remain largely unexplored.ObjectiveThis study focuses on the analysis of disagreements, which are described as an important part in the co‐production of knowledge in interaction.DesignA qualitative exploratory study using conversation analysis.Setting and participantsData were collected from a nurse‐led person‐centred intervention in a hospital outpatient setting. Interactions between adult patients with irritable bowel syndrome (n = 17) and a registered nurse were audio‐recorded. COREQ guidelines were applied.ResultsDisagreements were found after demonstration of the nurse''s or patients’ respective professional or personal knowledge. Disagreements were also evident when deciding on strategies for self‐management. Although negotiations between opposing views of the nurse and patient were seen as important, the patient generally claimed final authority both in knowing how IBS is perceived and in the right to choose self‐management strategies. The nurse generally oriented towards patient authority, but instances of demonstration of nurse authority despite patient resistance were also found.Discussion and conclusionsThis study provides information on how co‐production of knowledge and decisions occur in the context of a person‐centred care intervention. Negotiations between nurse and patient views require a flexible approach to communication, adapting interaction to each context while bearing in mind the patients having the final authority. To facilitate co‐production, the patient''s role and responsibilities in interaction should be explicitly stated.     

Determinants of patient activation and its association with cardiovascular disease risk in chronic kidney disease: A cross‐sectional study

BackgroundPatient activation describes the knowledge, skills and confidence in managing one''s own health. Promoting patient activation is being prioritized to reduce costs and adverse outcomes such as cardiovascular disease (CVD). The increasing prevalence of chronic kidney disease (CKD) presents a need to understand the characteristics that influence patient activation and the effect on health outcomes.DesignCross‐sectional study.Setting and participantsPatients with non‐dialysis CKD recruited from 14 sites (general nephrology and primary care) in England, UK.Outcome measuresPatient activation was measured using the PAM‐13. Demographic and health‐related variables, self‐reported symptom burden, health‐related quality of life (HRQOL), socioeconomic status (SES), were assessed as determinants of patient activation. Major CVD risk factors included hypertension, dyslipidaemia, obesity and hyperkalaemia.Results743 patients were included (eGFR: 32.3 (_SD17.1) mL/min/1.73 m², age 67.8 (_SD13.9) years, 68% male). The mean PAM score was 55.1 (_SD14.4)/100. Most patients (60%) had low activation. Those with low activation were older (P<.001), had lower eGFR (P = .004), greater number of comorbidities (P = .026) and lower haemoglobin (P = .025). Patients with low activation had a 17% greater number of CVD risk factors (P < .001). Risk factors in those with low activation were being older (P < .001) and having diabetes (P < .001).ConclusionThis study showed that only a minority of CKD patients are activated for self‐management. Our findings help better understand the level of activation in these patients, particularly older individuals with multimorbidity, and further the knowledge regarding the characteristics that influence activation.Patient or Public ContributionPatients were involved in the design of main study.