Feasibility outcomes
The primary outcome of this study is the feasibility of conducting a full RCT of the PRIDE intervention, determined by a range of measures related to the study objectives. The feasibility outcomes, which will be measured to meet the objectives of this study, are shown in Table 2.
Table 2: Feasibility Objectives and Outcomes
Feasibility Objectives
|
Feasibility Outcomes
|
1. Determine the feasibility of recruitment to a large-scale RCT
|
a. Aggregate data on potential participants within NHS services
b. Number of patients assessed for eligibility / consented / randomised
c. Number and proportion of potential participants identified through NHS services, Join Dementia Research and by self-referral who are eligible
d. Reasons for non-inclusion / non-eligibility
e. Monthly recruitment rate per site
f. Barriers and facilitators to recruitment ( focus groups)
|
2. Refine the eligibility criteria for a future definitive RCT
|
a. Number of screening failures for eligibility, post-consent
b. Participant and facilitator report (focus groups)
|
3. Determine the acceptability to patients / clinicians of randomisation
|
a. Proportion of eligible patients that consent to randomisation
b. Reasons for non-consent
c. Participant and facilitator report (focus groups)
|
4. Determine the relevance and acceptability to patients / clinicians of the trial intervention
|
a. Premature discontinuation or non-attendance of treatment and reasons
b. Feedback from participants and site staff delivering the intervention
c. Participant and facilitator report (focus groups)
|
5. Determine the acceptability to patients / clinicians of the trial procedures
|
a. Proportion of approached NHS sites that agree to participate in the trial and reasons for non-participation
b. Proportion of eligible patients that consent to randomisation
c. Reasons for non-consent
d. Withdrawals and losses to follow-up and reasons
e. Feedback from participants and staff (focus groups)
|
6. Assess the ability of NHS sites to deliver the intervention
|
a. Measures of the feasibility of delivering the PRIDE intervention within NHS settings:
i. Number / grade / experience of staff within the service
ii. Staff turnover
iii. Time to treatment initiation
b. Measures of the recruitment and retention of PRIDE facilitators during the study treatment period
c. Barriers to treatment delivery per protocol (focus groups)
|
7. Assess training and support needs for NHS staff delivering the intervention
|
a. Feedback on training delivered (focus groups)
b. Support offered / accepted (e.g. log of calls and emails to central support lines)
c.
|
8. Evaluate treatment fidelity when delivered through NHS services
|
a. Measures of treatment fidelity including:
i. Adherence to intervention manual
ii. Uptake of activities
b. Feedback from participants and staff (focus groups)
|
9. Determine the services and interventions provided as usual care and evaluate methods for measuring this
|
a. Post-diagnostic care pathway
b. Services available
c. Uptake of services
|
10. Assess follow-up and outcome completion rates
|
a. Response rate to follow-up assessment
b. Questionnaire completion rates
c. Amount of missing questionnaire data at item and scale levels
|
11. Determine the relevance and acceptability of a range of clinical outcome measures and selection of the primary outcome for the main trial
|
a. Completion rates and reasons for non-completion / missing data
b. Estimates of clinically important differences, variance and sensitivity to change for the clinical outcome measures
c. Direct questions to participants regarding relevance of measures
|
12. Evaluate the utility and acceptability of resource use questionnaires for use in an economic evaluation alongside a future RCT
|
a. Completion rate and reasons for non-completion / missing data
|
13. Comparative micro-costing of PRIDE intervention and usual care
|
a. Staff time and resources for delivery of PRIDE intervention
b. Other service use
|
14. Estimate the sample size required for a definitive study
|
a. Primary outcome selection
b. Variability in the outcome
c. Withdrawals and losses to follow-up
|
15. Determine the resources required for a full trial
|
a. Sample size, recruitment rate (number of sites / recruitment period), staffing and resources (for recruitment, treatment and follow-up)
|
Clinical outcomes
Clinical outcomes will be measured to assess the relevance and acceptability of these outcomes for use in a future definitive RCT and to obtain information to inform selection of the primary outcome measure for a future trial. The following clinical outcomes will be assessed at baseline and at follow-up visits completed at three and six months post-randomisation. Participants randomised after 30 June 2019 will not have a 6 month follow-up visit. For these participants the follow-up visit at 3 months will be their final visit:
Outcomes for the person with dementia
- Activities of Daily Living measured using the Lawton Instrumental Activities of Daily Living (IADL) Scale (18).
- Health related quality of life measured using the EuroQoL Quality of Life Questionnaire (EQ-5D-5L) (19)
- Quality of life measured using the DEMQOL (20)
- Mood measured using the Geriatric Depression Scale (GDS) – short form (21)
- Cognition measured using the Standardised Mini Mental State Exam (S-MMSE) (22)
- Wellbeing measured using the Control, Autonomy, Self-realisation and Pleasure (CASP) questionnaire (23)
- Quality of relationships measured using the Impact on Participation and Autonomy Questionnaire for older people (IPAQ-O) (24)
- Positive emotions measured using the Positive Psychology Outcome Measure (PPOM) (25)
- Social engagement measured using the number of social contacts and leisure activities per week
- Global change (assessed by the person with dementia and the supporter). At each follow-up time point, participants will be asked to provide a rating of their perceived change in relevant domains (wellbeing and sense of independence) since baseline, using a 5-point ordinal scale (much better, a bit better, no change, a bit worse, much worse).
Outcomes for supporters (if participating)
- Health related quality of life measured using the EuroQoL Quality of Life Questionnaire (EQ-5D-5L) (19)
Health economic outcomes
- Resource use measured using a modified version of the Client Service Receipt Inventory (CSRI) for dementia (26). Participants and supporters will be asked to provide a retrospective report of resource use in the preceding 3 months.
- Quality Adjusted Life Years (QALYs) calculated using health related quality of life data collected through the EQ-5D-5L and DEMQOL.
Micro-costing of the PRIDE intervention determined by collection of information from participating sites regarding the staff time and resources for delivery of the PRIDE intervention, including implementation, training and delivery.
Sample size
As this is a feasibility study, a formal sample size calculation for between group comparisons of a primary outcome is not appropriate. A sample size of 75 randomised participants will allow estimation of recruitment fraction with a margin of error (half-width of 95% confidence interval) of around 8 percentage points, and retention of 12 percentage points.
Recruitment
Recruitment started on 22 November 2018 and will end on 30 June 2019. Participants randomised after 30 June 2019 will not have a six-month follow-up visit. For these participants the follow-up visit at 3 months will be their final visit. Participants will be recruited from six secondary care sites in England. Whether identified in memory clinics, via PICs, through JDR or by self-referral, the investigator or their nominee, e.g. from the research team or a member of the participant’s usual care team, will inform the potential participant of all aspects pertaining to participation in the study and a written Participant Information Sheet will be provided.
Participants identified through JDR or by self-referral will be registered as outpatients of the memory clinic of the participating NHS trust at enrolment in the trial.
Participants will be advised that they can choose to take part either with a supportive other or on their own. If the participant chooses to take part with a supporter they will be asked to nominate a person, who if eligible, will be invited to join the study (note that it will also be possible for a supporter to assist the participant, without participating in the study in their own right). The potential supporter will be provided with written information about the study and be asked to attend the screening and baseline visit with the participant, where informed written consent will be obtained.
Consent
Trial participants have mild dementia, and therefore are generally expected to be competent to give informed consent for participation, provided that appropriate care is taken in explaining the research and sufficient time is allowed for them to reach a decision. If it is helpful for a supporter to be involved, we would aim to ensure that this is done wherever possible. In seeking consent, we will follow current guidance from the British Psychological Society on evaluation of capacity (27). In this context, consent has to be regarded as a continuing process and will be continually checked through discussion with participants during the assessments. If the participant's level of impairment increases during the course of their involvement in the study to the extent that, in the judgement of the investigator (or designee), they do not have capacity to provide continued informed consent for their ongoing participation in the trial at that time, the research activity would be discontinued.
Where a supporter is also participating in the trial, the supporter will be asked to provide written informed consent for their own participation in the trial. The supporter’s decision to participate or not will not affect involvement of the participant. Supporters may decline consent to participate in the trial on their own behalf but be present during and intervention sessions and researcher follow up appointments in order to support the person with dementia, should they request this. In this case, their involvement will be recorded but no further details or data will be collected.
Follow-up
Each participant will be in the trial for a maximum of six months, from randomisation to final follow-up. Table 3 describes the study procedures and assessments at each time point including screening and baseline. All baseline and follow-up visits will be completed face-to-face with a researcher.
Table 3: Study Procedures and Assessments
Months
|
0
|
0 – 2
|
3
|
66
|
Study Procedures and Assessments: Participants
|
Visit 1
|
RANDOMISATION
|
Intervention Period
|
Visit 2
|
Visit 3
|
Baseline
|
Follow-Up
|
Initial eligibility screen1
|
X
|
Intervention:
PRIDE intervention (3 sessions with a PRIDE facilitator) in addition to usual care
Control:
Usual care only
|
|
|
Informed consent2
|
X
|
|
|
Demographic information
|
X
|
|
|
Post-consent eligibility screen: Clinical Dementia Rating (CDR) Scale3
|
X
|
|
|
Lawton IADL Scale
|
X
|
X
|
X
|
EuroQoL Quality of Life (EQ-5D-5L)
|
X
|
X
|
X
|
DEMQOL
|
X
|
X
|
X
|
Geriatric Depression Scale (GDS)
|
X
|
X
|
X
|
Standardised Mini Mental State Exam (SMMSE)
|
X
|
X
|
X
|
Control, Autonomy, Self-realisation and Pleasure (CASP-19)
|
X
|
X
|
X
|
Impact on Participation and Autonomy (IPAQ-O) – Social Relations Sub-Scale
|
X
|
X
|
X
|
Positive Psychology Outcome Measure (PPOM)
|
X
|
X
|
X
|
Social Engagement Checklist
|
X
|
X
|
X
|
Global Change Measure
|
|
X
|
X
|
Client Service Receipt Inventory (CSRI)
|
X
|
X
|
X
|
Focus groups with facilitators and participants / supporters
|
|
X4
|
|
Study Procedures and Assessments: Supporters
|
Visit 1
|
Visit 2
|
Visit 36
|
Baseline
|
Follow-Up
|
Informed consent
|
X
|
|
|
Supporter questionnaire: EuroQoL Quality of Life (EQ-5D-5L)5
|
X
|
X
|
X
|
Global Change Measure5
|
|
X
|
X
|
Supporter questionnaire: Client Service Receipt Inventory (CSRI)5
|
X
|
X
|
X
|
1 Participants not included in the trial will be recorded on the screening log, with reasons for non-inclusion documented.
2 All participants providing consent will be enrolled on the trial database, with demographic details and screening assessments recorded.
3 Participants who are identified as ineligible for randomisation during the post-consent eligibility screen will be defined as screen failures and will not proceed to randomisation.
4 Separate focus groups will be completed with a facilitators and a subset of participants and supporters.
5 Supporter questionnaires will be passed to supporters during participant visits (if present) for completion during the visit or will be posted with a prepaid envelope for return to the Coordinating Centre.
6 Participants randomised after 30th June 2019 will not have a 6 month follow up visit, and their last visit will be at visit 2.
The duration of the trial is expected to be up to 24 months from recruitment of the first participant to reporting.
Withdrawal
Participants can withdraw from the trial at any time without affecting their current or future care. Reasons for withdrawal will be sought and recorded.
Participants in the intervention group may discontinue the PRIDE intervention at any time. Reasons for discontinuation from the intervention will be recorded. Participants who prematurely discontinue the trial intervention will be asked to remain in the trial for follow-up. If participants who prematurely discontinue the trial intervention choose to also withdraw from trial follow-up, the reason for withdrawal will be requested, and documented where given.
Supporters may also withdraw from the trial as a whole or choose to discontinue their involvement in the trial intervention. Doing so will not affect the participants continuation in the trial. The withdrawal or discontinuation of supporters will be recorded, with reasons for withdrawal or discontinuation requested, and documented where given. If the participant wishes to identify an alternative supporter to participate in the trial with them, they will be able to do so. The alternative supporter will provide consent to participate and the change of supporter will be documented.
Randomisation
Participants will be allocated at the individual level to intervention or control on a 1:1 ratio using minimisation with a probabilistic element. The minimisation variables will be study site, sex, age (< 80 or ≥ 80) and medication for dementia (any versus none). The allocation algorithm will be created by the Nottingham Clinical Trials Unit (NCTU) in accordance with their Standard Operating Procedure (SOP) and held on a secure server. The investigator or authorised designee will use the remote, internet-based randomisation system to obtain the treatment allocation for each participant.
Following randomisation, participants will be notified of their treatment allocation by an unblinded member of the research team and their GP will be notified of their involvement in the trial.
Blinding
Due to the nature of the intervention, blinding of treatment allocation is impossible for participants and the staff delivering it. The study outcome data at all the time points will be collected by members of the local research team who will be blind to group allocation. The researchers conducting the outcome assessment visits will record instances of unblinding. The trial statisticians will remain blinded to treatment allocation until after database lock.
Adverse events
No adverse reactions have been identified in previous trials of social and psychological interventions for people with dementia (9, 28, 29). The risks of the current trial have therefore been assessed as low and there are unlikely to be adverse events resulting from the trial. For this reason Adverse Events (AEs) and Serious Adverse Events (SAEs) will not be routinely collected for this trial.
The assessments for participants will be limited in duration and not unduly long or stressful. Researchers and facilitators delivering the intervention will be trained to identify and deal with any distress exhibited by trial participants during trial activities and will make referrals (e.g., to the participant’s GP) if needed.
Data collection, management and analysis
Data collection and clinical assessments will be in person with the researcher and conducted in the participant’s home (or other suitable community or NHS venue, as appropriate, depending on participant preference). Participant questionnaires at baseline, follow-up at three months and six months will be self-completed by participants during the visits. If the participant chooses to take part with a supporter, the designated supporter will be asked to complete questionnaires also at baseline and follow-up at three months and six months. If the supporter is not present during the follow-up visit, the questionnaire may be posted to them.
Data collection and retention rates will be monitored by the Trial Management Group (TMG) throughout the trial.
Statistical analyses
Data analysis will primarily be descriptive to address the feasibility aims of the study. All analyses will be documented in a Statistical Analysis Plan which will be finalised prior to database lock. Feasibility outcomes will be estimated using descriptive statistics (with 95% confidence intervals [CI] if relevant) and will include recruitment rates, follow-up rates, amount of missing data, and intervention adherence. The rate of protocol adherence will be reported within the intervention group in terms of participants who adhere to the intervention they were allocated to receive and who comply with the scheduled treatment visits.
Key baseline characteristics (age, gender) will be compared between trial participants and the ineligible and non-consenting patients, to ascertain adequacy of inclusion/exclusion criteria and likely generalisability of the trial to the required targeted population.
Similarly, we will compare the key patient characteristics between those followed-up and those lost to follow-up and investigate how similar this is across the treatment arms to assess possible attrition bias in data collection.
A baseline table will compare important demographic and clinical characteristics between the two treatment arms. It is not an objective of the feasibility study to obtain estimates of intervention effect on clinical outcomes and so the clinical outcomes will be presented descriptively.
Global change outcomes will be used to categorise improvers / non-improvers for anchor-based analysis of minimum clinically important differences and responsiveness to change of relevant, related outcome measures.
Trial management and oversight
Nottingham Clinical Trials Unit (NCTU) is the coordinating centre and responsible for all trial management activities. Trial oversight will be provided by an independent Trial Steering Committee (TSC) who will monitor trial progress and assess feasibility. As the trial interventions and procedures have been assessed as low risk, safety oversight will be performed by the TSC without the need for a separate independent Data Monitoring Committee.
The Trial Management Group (TMG) responsible for the day-to-day delivery of the trial will also meet monthly and report to the TSC on progress.
Qualitative sub-study
Facilitator and participant (supporters, where present) focus groups will be arranged to explore perspectives on the intervention and investigate a range of themes including, but not limited to:
- Acceptability of the intervention (manual, sessions, facilitation)
- Barriers and facilitators to delivery of the intervention
- Experience of the intervention
- Factors that may mediate or moderate the effectiveness of the intervention
- Skills and competencies required to deliver the intervention
- Barriers and facilitators to continued use of the intervention
- Acceptability of the outcome measures (quantity, content, ability to complete)
- Acceptability of the trial procedures (recruitment, consent, randomisation and activities throughout the follow-up period)
Utilising a focus group approach will help people to identify and clarify their views in relation to others who have experienced the same intervention (30) and support sharing of their ideas and similar or different opinions.
A schedule of topics and questions will help guide discussion to produce final themes (31). Field notes will be used to record discussions and agreement. Results will be used to explore potential explanations for the quantitative findings and identify emergent factors that influence the uptake and impact of the intervention and other trial procedures for a future large trial.
Protocol amendments
All methods described here reflect the current study protocol (V2.1 dated 19June2019). This protocol conforms to the SPIRIT recommendations (32). See Table 4 for a summary of protocol amendments. All amendments to the protocol have been approved by the trial sponsor, Research Ethics Committee and local R&D departments prior to implementation.
Table 4: Summary of amendments to the PRIDE feasibility study protocol
Protocol
|
Date
|
Summary of changes
|
2.0
|
20 Dec 2019
|
· GP practices added as Participant Identification Centres
· GHQ-12 questionnaire removed to reduce burden on participant and supporters in completing questionnaires
· Allowed sites the flexibility to manage the Join Dementia Research database to identify potential participants
|
2.1
|
22 May 2019
|
· Extension of the recruitment period for a month if required
· Participants randomised after 30th June 2019 will only have a 3 month follow up visit
|
Confidentiality
Participant confidentiality will be ensured by allocating participants a unique identification number to correspond to treatment data in the computer files.
If information is disclosed during the study that could pose a risk of harm to the participant or others, the researcher will discuss this with the CI and where appropriate report accordingly.
Data generated as a result of this trial will be available for inspection on request by appropriate organisations and bodies such as the REC and the regulatory authorities.