Protocol for the Feasibility Study of INSPIRE: an Individually Tailored Support Intervention for Informal Caregivers of Older Adults With Rheumatoid Arthritis and Frailty
Phase: NA
Conditions: Rheumatic Arthritis
Sponsor: Glostrup University Hospital, Copenhagen

 
 
 
Protocol for the Feasibility Study of INSPIRE: an Individu-
ally Tailored Support Intervention for Informal Caregivers 
of Older Adults With Rheumatoid Arthritis and Frailty 
Authors:  
Luise Holberg Lindgren a Signe Marie Abild a, Charlotte Werdal Hansen a, Tanja Thomsen c, Julie Midtgaard d,b, 
Katrine Piper e, Bente Glintborg a,b, Bente Appel Esbensen a,d 
 
Corresponding author: Luise Holberg Lindgren Mail: Luise.holberg.lindgren@regionh.dk 
 
Affilitations:  
a. 
Rigshospitalet, Center for Rheumatology and Spine Diseases, Center for Arthritis Research (COPECARE), 
Valdemar Hansens Vej 13, 2600 Glostrup, Denmark 
 
b. 
University of Copenhagen, Department of Clinical Medicine, Blegdamsvej 3B, 2200 Copenhagen, Den-
mark 
 
c. 
Bispebjerg and Frederiksberg Hospital, Center for Clinical Research and Prevention, Nordre Fasanvej 57, 
2000 Frederiksberg, Denmark 
 
d. 
Copenhagen University Hospital – Mental Health Services, Mental Health Center Glostrup, Centre for 
Applied Research in Mental Health Care (CARMEN), Nordstjernevej 41, 2600 Glostrup, Denmark,  
 
 
e. 
Copenhagen University Hospital, Department of Occupational Therapy and Physiotherapy, Blegdamsvej 
9, 2100 Copenhagen, Denmark,  
 
Trial registration: The study will be registered in a publicly accessible trial registry (e.g., ClinicalTrials.gov or 
ISRCTN) before recruitment begins. Registration ID will be added once available 
Document date: 02.02.2026 
 
 

 
Side 2
 
Abstract 
Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with pain, fatigue, 
functional limitations, and reduced quality of life. As more people live to older age with RA, age-re-
lated vulnerability such as frailty becomes increasingly relevant and may amplify functional decline, 
multimorbidity, and reliance on others. Informal caregivers (unpaid family members, friends, or neigh-
bors) often provide substantial practical, emotional, and coordination support, yet caregiver needs are 
frequently overlooked in rheumatology care. INSPIRE (INtervention to Support Partners and Informal 
caREgivers of frail patients with RA) is an individually tailored support intervention developed using 
the UK Medical Research Council framework for complex interventions and an iterative co-creation 
process involving older adults with RA and frailty, caregivers, healthcare professionals, and social care 
stakeholders. Before a definitive evaluation, feasibility and acceptability in routine care must be estab-
lished. 
Aim: To evaluate the feasibility and acceptability of delivering INSPIRE in routine rheumatology care 
and to test study procedures in preparation for a future definitive trial. 
Methods: This is a single-arm feasibility study recruiting 25 informal caregivers of older adults with RA 
and frailty. Recruitment will occur within a fixed four-month window (1 March–1 July 2026) and will 
not be extended. Care recipients (older adults) will be ≥65 years with RA and frailty classified as Clini-
cal Frailty Scale (CFS) 4–7. Caregivers will be ≥18 years, provide unpaid support, and report at least 
moderate burden defined as a Caregiver Burden Scale (CBS) mean score >1.99 at screening. Partici-
pants will be recruited from Rigshospitalet (Center for Rheumatology and Spine Diseases) and rheu-
matology departments in Køge, Slagelse, and Holbæk. Identification uses routine patient-reported out-
comes (DANBIO) with invitation of potentially frail patients (e.g., MDHAQ >1.0) followed by telephone 
screening and CFS assessment; eligible patients nominate a caregiver who is then screened using CBS. 
Intervention: INSPIRE is delivered by a trained healthcare professional over ~12 weeks and comprises 
three contacts: an initial consultation (60–90 min), a brief follow-up (15–30 min), and a final consulta-
tion (30–60 min). Content is tailored using a toolbox addressing validation of the caregiver role, emo-
tional/practical support, education, communication, and navigation across health and municipal ser-
vices. Involvement of the older adult in consultations is optional and based on preferences of both 
parties. 

 
Side 3
 
Outcomes: Feasibility outcomes include recruitment (screened/eligible/consented), retention at 12 
weeks, questionnaire completeness, and deliverability (session completion, mode, duration). Accepta-
bility will be assessed post-intervention using brief acceptability/feasibility questions and qualitative 
interviews with informal caregiver. Fidelity and tailoring will be documented using structured session 
notes. Exploratory outcomes include Care burden (CBS), quality of life (WHOQOL-BREF) (informal care-
giver and older adult), and physical function (MDHAQ). 
Progression criteria: Pre-specified criteria include approximately 50% recruitment of those ap-
proached, ≥85% retention, and high fidelity, reviewed using a traffic-light approach (go/amend/stop). 
Ethics and dissemination: Written informed consent will be obtained from both the older adult and 
the informal caregiver prior to baseline data collection, with separate consent for any study compo-
nents each participant takes part in (e.g., consultations, interviews). Findings will be disseminated 
through peer-reviewed publication, conferences, stakeholder summaries and patient organizations. 
Trial registration: The study will be registered in a publicly accessible registry (e.g., ClinicalTrials.gov or 
ISRCTN) prior to recruitment; the registration ID will be added when available. 
 
 

 
Side 4
 
Background  
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the 
joints and is associated with pain, stiffness, swelling, reduced function, and fatigue, and it can also af-
fect other organs and overall well-being [1,2] . Mental health problems are common in RA; depression 
in particular is associated with higher pain and disability and lower health-related quality of life [3,4]. 
As more people live longer with RA, an increasing proportion of patients reach older age, where age-
related vulnerability such as frailty becomes more relevant; epidemiological data show that RA burden 
and occurrence increase with age [5].  
Frailty is commonly described as a state of increased vulnerability to stressors due to reduced physio-
logical reserve across multiple systems, which increases the risk of adverse outcomes and fluctuating 
functional capacity [6]. In community-dwelling older adults, frailty is prevalent, with estimates varying 
by definition and setting but consistently demonstrating that a substantial proportion of adults aged 
65 years and older are affected [7]. In older adults living with both RA and frailty, functional decline 
and multimorbidity can increase reliance on others in daily life. 
In this context, informal caregivers (unpaid family members, friends, or neighbors) often become cen-
tral contributors to everyday disease management, including practical support, coordination, and 
treatment/medication-related tasks [8]. Health systems also increasingly depend on the capacity of 
patients and families to manage chronic illness in the community; evidence shows that family caregiv-
ers are linked with fewer and shorter hospital stays for older adults, illustrating the system-level im-
portance of caregiving contributions [9]. However, these responsibilities can place substantial emo-
tional and practical demands on caregivers. 
These demands may lead to caregiver burden, a multidimensional strain encompassing emotional, 
physical, social, and financial aspects of providing care [10]. Caregiver burden is associated with ad-
verse caregiver outcomes, including distress and reduced health and quality of life, and it is often 
overlooked in clinical practice [11]. Although interventions for caregivers in other chronic disease pop-
ulations suggest that psychosocial and educational support can reduce distress and burden and im-
prove quality of life, structured caregiver support remains limited in rheumatology care and is rarely 
implemented systematically for caregivers of older adults with RA and frailty [12].  

 
Side 5
 
INSPIRE (INtervention to Support Partners and Informal caREgivers of frail RA patients) was developed 
using the UK Medical Research Council (MRC) framework for complex interventions (REF) and an itera-
tive co-creation process involving older adults with RA and frailty, informal caregivers, healthcare pro-
fessionals, and social care stakeholders. INSPIRE is designed to recognize and validate the caregiver 
role, provide emotional and practical support, and facilitate navigation and coordination across frag-
mented services through a tailored “toolbox” delivered by trained healthcare professionals over ap-
proximately twelve weeks. Before evaluating effectiveness, a feasibility study is required to assess re-
cruitment, acceptability, delivery, and data collection procedures in routine clinical practice. 
 
Aim and objectives 
The overall aim is to evaluate the feasibility and acceptability of delivering INSPIRE in routine rheuma-
tology care and to test study procedures for a future definitive evaluation.  
Comprising the feasibility of: 
• 
Identifying and recruiting eligible caregiver participants, retaining participants through follow-
up, collecting outcome data with acceptable completeness, and delivering the intervention as 
intended 
Explore: 
• 
Perceived usefulness of the intervention, acceptability of the intervention, Implementation 
barriers and facilitators among:  
o 
Caregivers 
o 
Older adults 
o 
Intervention-delivering professionals 
Provide preliminary estimates of outcome variability to inform: 
• 
Selection of outcomes for a subsequent trial and sample size planning for a subsequent trial 
 

 
Side 6
 
Progression criteria 
Progression to a definitive evaluation will depend  on whether recruitment and retention are ade-
quate; whether the intervention can be delivered as intended within routine practice; whether out-
come measures are acceptable and sufficiently complete; and whether participants and healthcare 
professionals consider INSPIRE relevant and acceptable. Pre-specified thresholds (e.g., minimum con-
sent and follow-up rates) will be agreed and reviewed with stakeholders. 
 
Methods 
Study design 
This study is a feasibility study designed to assess whether INSPIRE and the planned trial procedures 
are deliverable and acceptable This study is designed to evaluate progression criteria in preparation 
for a full-scale RCT and to identify areas where adjustments of the intervention and/or study design 
were needed. Our progression criteria include a 50% recruitment rate of all patients approached, an 
85% retention rate, and overall high fidelity. 
 
Study setting 
The study will be conducted at the Center for Rheumatology and Spine Diseases, Rigshospitalet (Den-
mark), with intervention delivery across the Capital Region and Region Zealand. Consultations will take 
place in the outpatient clinic, in caregivers’ homes, and/or by telephone according to informal caregiv-
ers  preference and feasibility. 
 
Recruitment window and stopping rule 
Recruitment will take place within a fixed four-month window from 1 March to 1 July 2026 and will 
not be extended. If the planned sample size is not reached by 1 July, recruitment will nonetheless stop 
at the end of the recruitment window, and the study will proceed with participants already enrolled 
(including completion of follow-up). 

 
Side 7
 
Participants and eligibility 
The primary participants are informal caregivers of older adults with RA and frailty. Informal caregivers 
will be eligible if they are aged ≥ 18 years, provide unpaid support to an older adult aged ≥ 65 years 
with a confirmed RA diagnosis, and are able to provide informed consent and complete study ques-
tionnaires. Informal caregivers must report at least moderate burden, defined as a mean score above 
1.99 on the Caregiver Burden Scale (CBS) at screening. 
The care recipient must meet a pre-specified frailty criterion assessed in routine care, by the Clinical 
Frailty Scale (CFS), with eligibility defined as CFS 5 or higher. Older adults with RA and frailty are not 
the primary intervention recipients but may be involved in selected consultations if both parties be-
lieve it is relevant. Separate consent will be obtained from older adults for any involvement and for 
any linkage of clinical information. The care recipient must consent to the primary participants (infor-
mal caregiver) participation. 
Informal caregivers will be excluded if participation is not possible due to severe cognitive impairment, 
acute mental health crisis, or other circumstances that make it impracticable to complete the inter-
vention and follow-up. 
 
Sample size 
This study is a feasibility study designed to assess whether INSPIRE and the planned trial procedures 
are deliverable and acceptable, rather than to test effectiveness. In line with CONSORT guidance for 
pilot and feasibility trials and NIHR guidance [13,14], a formal power calculation based on clinical out-
comes is therefore not appropriate; instead, the sample size is chosen to provide sufficiently informa-
tive estimates of key feasibility parameters (recruitment, retention, and intervention delivery/fidelity) 
and to identify areas requiring modification before a full-scale RCT.  
We will aim to include 25 informal caregivers in this single-arm feasibility study within the fixed re-
cruitment window. This sample size is considered adequate for evaluating our progression criteria and 
informing decisions using a traffic-light approach (go/amend/stop), as recommended for feasibility 
work [15,16]. With a target recruitment rate of 50% of those approached, enrolling 25 participants 
corresponds to approaching approximately 50 eligible caregivers during the recruitment period. If 

 
Side 8
 
25/50 are recruited (50%), the 95% confidence interval for the recruitment proportion is expected to 
be approximately 0.37 to 0.63, which is sufficiently precise to detect clearly inadequate recruitment 
(e.g., around 30% or lower) and to guide procedural amendments if needed [13,17].  
For retention, with 25 enrolled and a progression target of 85%, we would expect approximately 21–
22 participants to complete follow-up. The corresponding 95% confidence interval around an ob-
served retention proportion close to this target remains informative for feasibility decision-making 
(e.g., for 21/25, ~0.65–0.94; for 22/25, ~0.70–0.96), and the combination of quantitative retention es-
timates with qualitative feedback will allow us to determine whether any loss to follow-up is accepta-
ble and modifiable before scaling to a definitive RCT [17,18].  
Finally, the sample provides sufficient exposure to assess intervention delivery and fidelity in practice. 
As INSPIRE includes three consultations over 12 weeks, inclusion of 25 caregivers will generate approx-
imately 75 intervention contacts, enabling structured fidelity documentation, identification of imple-
mentation challenges, and refinement of training and materials, which is the central purpose of feasi-
bility evaluation [15]. In addition, a sample of this size is consistent with common feasibility study tar-
gets reported in reviews of pilot and feasibility studies and is appropriate for informing a subsequent 
definitive trial [13,17]. 
 
Recruitment  
Informal caregivers of older adults diagnosed with RA will be recruited from the Department of Rheu-
matology and Spine Diseases at Rigshospitalet, Denmark, and the Departments of Rheumatology in 
Køge, Slagelse, and Holbæk. Eligible patients (care recipients) will be aged ≥65 years and classified as 
frail with a Clinical Frailty Scale (CFS) score of 4–7. 
Patients with RA are routinely invited to complete patient-reported outcomes in the Danish National 
Clinical Rheumatology Registry (DANBIO) [19] prior to outpatient visits. Frailty is not currently assessed 
in DANBIO; however, the Multidimensional Health Assessment Questionnaire (MDHAQ), which cap-
tures functional ability, disability, and capacity to perform activities of daily living, is included. MDHAQ 
scores are known to correlate with frailty [20]. A score of ≥1.3 on the Health Assessment Question-
naire Disability Index (HAQ-DI) has been shown to correspond to very mild frailty, and HAQ-DI can be 

 
Side 9
 
converted to an MDHAQ score using the algorithm: MDHAQ = (HAQ-DI/1.08) − 0.15 [21,22]. On this 
basis, all patients aged ≥65 years with RA attending the participating departments between March and 
August 2026 who score >1.0 on the MDHAQ will be invited to receive additional information about the 
study. The invitation will appear as a pop-up at the screen when patients complete the DANBIO ques-
tionnaires, allowing them to indicate interest (yes/no) in the INSPIRE project. 
Patients who indicate interest will receive detailed written information and will subsequently be con-
tacted by telephone by a member of the study team to receive verbal information and to address any 
questions. Eligibility will then be assessed using the CFS to determine frailty status. The CFS is a widely 
used and well-validated instrument in both international research and Danish clinical practice [23,24]. 
CFS evaluates domains including comorbidity, function, and cognition to generate a frailty score rang-
ing from 1 (very fit) to 9 (terminally ill) [23]. We selected the CFS range 4–7 to capture variation in 
frailty, from very mild frailty (CFS 4) to severe frailty (CFS 7). 
If a patient meets the eligibility criteria (CFS 4–7, age ≥65 years, and RA diagnosis), the study team will 
ask the patient to identify an informal caregiver (e.g., spouse/partner, family member, or close friend). 
The informal caregiver will be contacted by the study team and provided with written information 
about the study. Caregivers who express interest will be screened using the CBS to confirm eligibility. 
Caregivers should have a CBS score indicating moderate or greater burden. See Figure 1 for recruit-
ment flow. 

 
Side 10
 
 
Figure 1. Flow chart 
Consent procedures 
Written informed consent will be obtained from both the older adult with RA and the informal care-
giver prior to baseline data collection Each participant (older adult and informal caregiver) will provide 
their own consent. 
 
Intervention 
INSPIRE is delivered by a trained healthcare professional with rheumatology expertise and experience 
in psychosocial support and service navigation. The intervention runs over approximately twelve 
weeks and includes an initial consultation, follow-up, and a final consultation. The initial consultation 
(about 60–90 minutes) takes place at home or in the clinic and is guided by the caregiver’s CBS profile. 

 
Side 11
 
The consultation focuses on recognizing and validating the caregiver role, identifying the most burden-
some issues, exploring underlying causes, and establishing realistic goals. Based on the needs identi-
fied, the informal caregiver is introduced to a tailored toolbox of resources and referral pathways that 
may include emotional or psychological support options, guidance on managing practical and physical 
strain, support for social isolation, communication and relationship support, disease-related educa-
tion, and assistance navigating municipal and health system services such as home care, assistive de-
vices, or case management. 
The second consultation is a brief follow-up contact (typically by phone, about 15–30 minutes) and 
used to review progress and adjust goals and support plans together with informal caregiver.  
The final consultation (about 30–60 minutes, phone or face-to-face) takes place within twelve weeks 
and focuses on evaluating the intervention experience, reviewing outcomes, and planning any ongoing 
support needs. Involvement of the older adult is optional and can be included in later consultations 
when considered relevant and desired by both informal caregiver and older adult. 
 
Outcomes and data collection 
Feasibility outcomes will describe recruitment (screened, eligible, consented) within the fixed recruit-
ment window, retention at 12 weeks, completeness of questionnaire data, and the practicality of de-
livering INSPIRE (session completion, delivery mode, and session duration).  
Acceptability will be assessed using brief post-intervention acceptability questions and qualitative in-
terviews.  
Fidelity and tailoring will be documented using structured session notes indicating whether core com-
ponents were delivered, and which toolbox elements were selected. 
Caregiver burden will be measured using the CBS. The CBS is a 22-item self-report questionnaire cov-
ering five domains (general strain, isolation, disappointment, emotional involvement, and environ-
ment) with responses typically scored on a 4-point scale; higher scores indicate higher perceived bur-
den [26,27]. The CBS has demonstrated validity and reliability in its original development [26], and the 

 
Side 12
 
Danish version has shown good internal consistency (total scale Cronbach’s alpha around 0.93) with-
out marked floor/ceiling effects, supporting its use for caregiver populations in Denmark [28].  
Quality of life will be measured using WHOQOL (World Health Organization Quality of Life) for both 
caregivers and patients (older adults with RA and frailty), using the WHOQOL-BREF (brief) format. 
WHOQOL-BREF is a 26-item generic quality-of-life instrument covering four domains (physical, psycho-
logical, social relationships, and environment) plus overall QoL/general health items, developed by the 
World Health Organization for cross-cultural use [29]. Psychometric evaluations have shown good to 
excellent reliability and evidence of validity across field trials and settings [29], and the Danish transla-
tion has been evaluated and found psychometrically acceptable, supporting its use in Danish samples 
[30]. Each item is rated on a 5-point Likert scale with values ranging from 1 to 5 (minimum = 1; maxi-
mum = 5). Higher scores indicate better quality of life / better perceived health. Domain scores are 
typically calculated by summing relevant items and transforming to a standardized scale; regardless of 
transformation, higher domain scores represent better quality of life. 
Physical function will be assessed using the physical function section of the Multidimensional Health 
Assessment Questionnaire (MDHAQ) in both the older adults with RA and frailty and their informal 
caregivers. The MDHAQ physical function scale comprises 10 activities of daily living, each scored on a 
0–3 scale (from no difficulty to unable to do), and will be summarized as a total score (commonly re-
ported as a 0–10 raw sum or transformed to a 0–3 metric), with higher scores indicating greater func-
tional limitation [31,32]. In patients with rheumatic disease, MDHAQ function is widely used as a prag-
matic, low-burden measure for routine care and research [33,34]. For informal caregivers, MDHAQ 
function is used here as a generic self-reported indicator of everyday functional capacity rather than a 
disease-specific disability measure; a key limitation is that measurement properties and interpretabil-
ity (including responsiveness and clinically meaningful thresholds) are less well-established in caregiver 
populations, and floor/ceiling effects may be more pronounced if many caregivers have minimal func-
tional limitations [35,36]. Therefore, we will interpret caregiver MDHAQ function scores descriptively, 
and will report score distributions and the proportion at the floor/ceiling alongside data completeness 
at baseline and follow-up; where helpful, we will contextualize patterns using available population-
based functional disability benchmarks from HAQ-type instruments [37]. 

 
Side 13
 
Questionnaire data will be collected using REDCap [38]. Participants will complete questionnaires elec-
tronically, and responses will be entered and stored directly within the REDCap platform to support 
standardized, secure data capture and management. 
 
Qualitative evaluation 
A purposive sample of caregivers, based on age sex and relation to the frail older adult, will be invited 
for semi-structured interviews after completing the intervention to explore perceived relevance, ben-
efits, burdens, and suggestions for improvement. A subset of older adults who were participated  in 
consultations may also be interviewed to capture dyadic perspectives. The healthcare professional de-
livering the intervention will interview to explore implementation barriers, facilitators, and resource 
implications. Data will be analyzed using thematic analysis, guided by the INSPIRE logic model (REF) 
and feasibility domains. 
Table 1. Schedule of enrolment, interventions, and assessments  
Study period 
Enrolment 
Baseline  
Post-allocation (in-
tervention period) 
Close-out 
Timepoint 
Screening - during 
recruitment window 
Week 0 
Weeks 0-12 
Week 12 
ENROLMENT 
Identification via routine clinic pathway (DANBIO 
pop-up for RA patients with MDHAQ > 1.0) 
X 
 
 
 
Telephone information to patient and frailty screen-
ing 
X 
 
 
 
Clinical Frailty Scale (CFS) for older adult eligibility 
X 
 
 
 
Caregiver contact and study information 
X 
 
 
 
Caregiver Burden Scale (CBS) eligibility screening 
(mean > 1.99) 
X 
 
 
 
Informed consent (informal caregiver and older adult 
with RA) 
X 
 
 
 
INTERVENTION 
INSPIRE delivery (tailored toolbox; validation/goal-
setting/navigation support) 
 
 
X 
 
INSPIRE brief follow-up contact (progress review/ad-
justment) 
 
 
X 
 
INSPIRE final consultation (review/ongoing plan) 
 
 
X 
 
FEASIBILITY OUTCOMES 

 
Side 14
 
Recruitment metrics (screened/eligible/ap-
proached/consented; reasons) 
X 
 
 
 
Retention (follow-up completion; withdrawals and 
reasons) 
 
 
 
X 
Intervention deliverability (sessions completed; 
mode; duration) 
 
 
X 
X 
Fidelity and tailoring documentation (core compo-
nents delivered; toolbox elements selected) 
 
 
X 
X 
Data completeness (item/scale completeness for 
questionnaires) 
 
X 
 
X 
Post-intervention acceptability  
 
 
 
X 
Harms/distress monitoring and signposting/referral if 
needed 
 
X 
X 
X 
CAREGIVER AND PATIENT-REPORTED OUTCOMES (EXPLORATORY) 
Caregiver burden (CBS) 
 
X 
 
X 
Caregiver quality of life (WHOQOL-BREF) 
 
X 
 
X 
Older adult quality of life (WHOQOL-BREF) 
 
X 
 
X 
Caregiver physical function (MDHAQ) 
 
X 
 
 
QUALITATIVE EVALUATION (POST-INTERVENTION) 
Informal caregiver semi-structured interview (purpos-
ive sample) 
 
 
 
X 
Older adult semi-structured interview (subset; if in-
volved in consultations) 
 
 
 
X 
Delivering professional semi-structured interview 
 
 
 
X 
CBS = Caregiver Burden Scale; CFS = Clinical Frailty Scale; RA = rheumatoid arthritis; T0 = baseline; T1 = 12-week follow-up; WHOQOL-BREF = 
World Health Organization Quality of Life – BREF. 
 
Analysis 
Statistical methods 
Analyses will be descriptive. Recruitment, retention, completeness, and deliverability will be summa-
rized with proportions and appropriate uncertainty (e.g., confidence intervals where useful). CBS and 
WHOQOL-BREF outcomes will be summarized at baseline and follow-up, and exploratory pre–post 
changes will be presented with effect size estimates and confidence intervals without formal hypothe-
sis testing.  
 
 

 
Side 15
 
Qualitative analysis´ 
Qualitative findings will be analyzed thematically and integrated with quantitative feasibility findings 
to inform refinement of both the intervention and trial procedures. 
 
Data management and confidentiality 
Data will be handled in accordance with GDPR and Danish data protection requirements, stored se-
curely with access control, and reported in anonymized form. Linkage keys will be stored separately 
from study datasets.  
 
Monitoring and harms  
The study is low risk and involves no invasive procedures. Some participants may experience emo-
tional discomfort when discussing caregiving challenges; participants may pause or stop at any time. 
Delivering professionals will follow pre-defined pathways for signposting or referral if distress is identi-
fied. 
 
Ethics  
In accordance with Danish legislation, this study was assessed as not requiring approval by the Re-
gional Scientific Ethical Committee and was registered accordingly (registration no. F-25068393). The 
project was accepted and registered by the Danish Data Protection Agency (journal number:XXXXX). 
The principles of the Declaration of Helsinki will be followed.  
Before signing informed consent, the participants will receive written and oral communication.  While 
orally communicating information about the study, it will be determined whether the patient fulfills 
the criteria for participation. The patients will be screened for eligibility according to the inclusion and 
exclusion criteria. Following the meeting, they are offered 3 days to consider their decision. Only after 
signing the informed consent form, they are enrolled in the trial.  

 
Side 16
 
 
Patient and public involvement 
INSPIRE was developed through a stakeholder-informed co-creation process involving older adults 
with RA and frailty, informal caregivers, caregiver mentors, healthcare professionals and social care 
stakeholders, drawing on co-creation principles and prototyping guidance [39]. In line with EULAR rec-
ommendations on involving patient research partners in rheumatology research, patient partners con-
tributed during the development work, and involvement processes will be evaluated using the PEIRS-
22 measure of meaningful engagement [40]. Reporting of patient and public involvement in outputs 
from the feasibility study will follow GRIPP2 guidance where applicable [41].  
 
Dissemination 
Results will be disseminated through a least one peer-reviewed publication, conference presentations, 
and accessible summaries shared with participants, patient organizations, and clinical and municipal 
stakeholders, with the aim of informing refinement and planning of a subsequent effectiveness evalu-
ation. 
 
Expected findings 
This feasibility study is expected to show whether INSPIRE can be delivered as intended within routine 
rheumatology care and whether informal caregivers perceive the intervention as relevant and ac-
ceptable. We anticipate that the planned recruitment pathway, using routine patient-reported out-
comes and targeted screening for frailty followed by identification of an informal caregiver, will be 
practicable but may require refinement to optimize reach. In particular, we expect that not all eligible 
older adults will be willing or able to nominate an informal caregiver, and that caregiver consent rates 
may vary depending on perceived time demands, relationship dynamics, and current caregiving strain. 
Regarding deliverability, we expect that the three consultations over approximately twelve weeks will 
be manageable within clinical workflows when supported by structured session notes and a defined 
toolbox. We anticipate that tailoring will be central to acceptability, with different informal caregivers 

 
Side 17
 
drawing on different toolbox elements depending on whether their burden is primarily related to 
emotional distress, practical strain, social isolation, or challenges navigating municipal and healthcare 
services. Fidelity documentation is expected to demonstrate that core components (recognition/vali-
dation, goal-setting, and navigation support) can be delivered consistently while allowing individual-
ized emphasis. 
For study procedures, we expect acceptable retention and questionnaire completeness at 12 weeks, 
although some missing data may occur among informal caregivers experiencing high strain or compet-
ing responsibilities. While the study is not designed to test effectiveness, exploratory pre–post sum-
maries are expected to indicate whether the selected outcome measures are responsive and feasible 
in this population. We anticipate potential signals in the expected direction, particularly reduced care-
giver burden and improved aspects of quality of life, alongside qualitative accounts describing in-
creased validation, clearer pathways for support, and improved confidence in managing and coordi-
nating care. Together, the quantitative feasibility metrics and qualitative feedback will inform whether 
progression criteria are met and what amendments are needed before a definitive evaluation. 
 
Study limitations 
As a single-arm feasibility study with a small sample size, the study cannot determine intervention ef-
fectiveness, and any observed changes in informal caregiver burden or quality of life must be inter-
preted cautiously because they may reflect regression to the mean, natural variation, or contextual 
influences rather than intervention impact. The limited sample will also restrict precision in estimating 
feasibility parameters and will reduce the ability to explore differences across caregiver subgroups or 
across levels of frailty. 
The study is conducted within specific clinical and regional contexts, which may limit transferability to 
other healthcare systems and service configurations, particularly where access to municipal supports, 
or rheumatology follow-up differs. Recruitment may be subject to selection effects because participa-
tion depends on older adults indicating interest, being reachable for screening, and nominating an in-
formal caregiver, and because caregivers must report at least moderate burden to be eligible; conse-
quently, findings may not represent informal caregivers with low burden, those reluctant to identify as 
caregivers, or those in strained relationships where participation is less likely. The fixed recruitment 

 
Side 18
 
window may further constrain representativeness by capturing a limited period of clinic flow and staff-
ing conditions. 
Finally, feasibility and acceptability outcomes rely largely on self-report questionnaires and interviews, 
which may be influenced by social desirability and differing interpretations of burden and quality-of-
life items. The 12-week follow-up may be sufficient to assess short-term feasibility and perceived use-
fulness but may not capture sustainability of benefits, longer-term service navigation outcomes, or de-
layed changes in caregiver strain. These limitations are acceptable for a feasibility study and will be 
used to guide refinement of recruitment procedures, outcome selection, follow-up timing, and the de-
sign of a future definitive evaluation. 
 

 
Side 19
 
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Ajeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical 
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https://doi.org/10.1177/1759720X17720366. 
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