Background
Introduction
‘…a RCT in which an intervention (or several interventions) to enhance recruitment outcomes are tested in the context of another RCT (or several RCTs) known as the host RCT(s)’.
Rationales for the study
Objectives of the study
Primary objective
Secondary objectives
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Recruitment rate 61–120 days post teleconference
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We will compare the recruitment 60 days post teleconference with a baseline inclusion from 1 Sep 2017 to 31 Oct 2017 for all centres. The purpose is to see if there is any bias or impact during the course of the study
Hypothesis
The rationale for the trial design
Methods
Study settings
Study type
Centre | Type of centre | Number of stroke patients per yeara | First included patient in EFFECTS (yyyy-mm-dd) | Total number of patients recruited | Percentage of number of patients recruitedb |
---|---|---|---|---|---|
01 Danderyd Hospital | SU at hosp | 837 | 11/11/2014 | 110 | 14% |
02 Karolinska University Hospital Solna | SU at univ hosp | 542 | 10/20/2014 | 98 | 12% |
03 Skaraborg Hospital Skövde | SU at hosp | 422 | 10/20/2014 | 56 | 7% |
04 Hässleholm Hospital | SU at hosp | 203 | 3/23/2015 | 32 | 4% |
05 Uppsala University Hospital | SU at univ hosp | 496 | 4/20/2015 | 39 | 5% |
06 Karolinska University Hospital Huddinge | SU at univ hosp | 488 | 4/8/2015 | 15 | 2% |
07 Mora General Hospital | SU at hosp | 226 | 4/15/2015 | 49 | 6% |
08 Falu General Hospital | SU at hosp | 510 | 5/13/2015 | 12 | 1% |
09 Lidköping | SU at hosp | 162 | 10/6/2015 | 12 | 1% |
10 Capio St Göran’s | SU at hosp | 697 | 6/24/2015 | 51 | 6% |
11 Visby General Hospital | SU at hosp | 132 | 11/4/2015 | 7 | 1% |
12 Norrland University Hospital | SU at univ hosp | 355 | 9/22/2015 | 12 | 1% |
13 Kristianstad Central Hospital | SU at hosp | 334 | 9/24/2015 | 11 | 1% |
14 Norrtälje Hospital | SU at hosp | 165 | 12/9/2015 | 1 | 0% |
15 Helsingborg General Hospital | SU at hosp | 391 | 11/18/2015 | 15 | 2% |
16 Skåne University Hospital Malmö | SU at univ hosp | 478 | 12/18/2015 | 16 | 2% |
17 Halland Hospital Halmstad | SU at hosp | 374 | 12/1/2015 | 36 | 4% |
18 Mälar Hospital Eskilstuna | SU at hosp | 246 | 2015-22-23 | 10 | 1% |
19 Rehab Station Stockholm | Neuro RH |
c
| 11/24/2015 | 4 | 0% |
20 Skåne University Hospital Lund | SU at univ hosp | 634 | 2/29/2016 | 9 | 1% |
21 Sundsvall Hospital | SU at hosp | 486 | 12/18/2015 | 66 | 8% |
22 Sahlgrenska University Hospital | SU at univ hosp | 789 | 4/15/2015 | 16 | 2% |
23 Högsbo Rehabilitation Hospital | Neuro RH |
c
| 3/4/2016 | 2 | 0% |
24 Stora Sköndal Neurological Rehabilitation Clinic | Neuro RH |
c
| 1/22/2016 | 13 | 2% |
25 Östersund Hospital | SU at hosp | 339 | 3/10/2016 | 21 | 3% |
26 Alingsås General Hospital | SU at hosp | 223 | 2/25/2016 | 34 | 4% |
27 Ängelholm Hospital | SU at hosp | 232 | 3/15/2016 | 16 | 2% |
28 Stockholm Nursing Home | Neuro RH |
c
| 4/4/2016 | 13 | 2% |
29 Örebro Rehabilitation Clinic | Neuro RUH |
c
| 10/10/2016 | 10 | 1% |
30 Norra Älvsborg County Hospital Trollhättan | SU at hosp | 699 | 12/3/2016 | 4 | 0% |
31 Bromma Geriatric Clinic | Ger RH |
c
| 11/24/2016 | 1 | 0% |
32 Västmanland Hospital Västerås | SU at hosp | 411 | 1/18/2017 | 9 | 1% |
33 Dalen Hospital | Ger RH |
c
| 5/22/2017 | 2 | 0% |
34 Lindesberg General Hospital | SU at hosp | 117 | 6/15/2017 | 2 | 0% |
35 Hudiksvall Hospital | SU at hosp | 187 | 4/12/2017 | 6 | 1% |
Total | 810 | 100% |
Inclusion criteria
Exclusion criteria
Preparation before the intervention
The intervention – a structured teleconference
Post meeting agenda
Refusing to participate in the study
Statistics
Sample size and randomisation
Blinding
Statistical methods
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Sixty days pre-teleconference: 60 individuals
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Sixty days post-teleconference: 78 individuals
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That is, 78/60 = 1.3; a 30% increase in recruitment
Planned subgroup analyses:
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Are there any differences in recruitment rate between a medium recruiting centre versus a low recruiting centre?
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To what extent does the size of the stroke unit contribute to the number and percentage of patients included? Are there any differences between large stroke units versus small stroke units?
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Are there any differences between stroke units versus rehabilitation centres?
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Are there any differences between university hospitals versus non-university hospitals?
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Are there any differences between experienced centres versus non-experienced centres?
Recruitment
Explanation of the randomised, stepped-wedge design
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Step 1 starts with a 60-day running-in period beginning in September 2017, and consists of at least one medium and one low recruiting centre. The teleconference is performed at the end of October 2017, and the observation follows 60 days post intervention
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Step 2 starts with a 60-day running-in period beginning in October 2017, and consists of at least one medium and one low recruiting centre. The teleconference is performed at the end of November 2017, and the observation follows 60 days post intervention
Harm
Problems
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It is possible that the intervention will develop during the course of the study. At the beginning we will have a clear agenda, but it is possible that we will learn through the process, and that the intervention will become a little different
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It is also possible that the participants at the centres that have not yet been intervened with will find out about the interventions and will change their pattern of behaviour before the intervention takes place
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The organisation of the intervention will be challenging because it involves more than 27 centres over a period of 1 year
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At some centres, the head of the department will not be able to join during the structured telephone conference
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It is possible some centres will refuse to be a part of the intervention and this will interfere with the results
Discussion and generalisability
Limitations
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One limitation is that we will not include the top recruiters. However, we believe that the high recruiting centres have reached their maximum level of recruitment and the intervention will only have a minor effect
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It is possible that the intervention is too weak to have positive results. After all, we are trying to change the pattern of behaviour for over 60 persons and behaviour change is one of the hardest things to accomplish
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Since we started the EFFECTS study, we have already tried different things to identify barriers and find ways to enhance recruitment, so it may be that there is nothing more to be done
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We are planning to carry out multiple sub-group analyses. The results must be interpreted with caution
Trial status
Acknowledgements
Funding
Availability of data and materials
Study sponsor
Management
Coordination centre
Steering Committee
Dissemination policy
Members of the Steering Committee
Data management
Database design | EDC Scandinavia |
e-CRF design | EDC Scandinavia, Karolinska Institutet and Karolinska Trial Alliance |
Server management | EDC Scandinavia |
Data collection | Centre and Karolinska Institutet |
Data manager | EDC Scandinavia |
Case Report Form (CRF) annotation | Centre, Karolinska Institutet and Karolinska Trial Alliance |
Data entry | Centre, Karolinska Institutet and Karolinska Trial Alliance (only central 6 and 12 months) |
Monitoring | Karolinska Trial Alliance |
Source data verifications | Karolinska Trial Alliance |
Issue and resolve data correction forms | Karolinska Institutet and Karolinska Trial Alliance |
Medical coding | Karolinska Institutet |
Data validation | EDC Scandinavia and Karolinska Institutet |
Discrepancy management | Centre, Karolinska Institutet and Karolinska Trial Alliance |
Database lock. The database will be preserved according to Karolinska Institutet’s rules, the electronic notebook [18] | EDC Scandinavia |
Data Monitoring Committee (DMC)
Review meetings
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Safeguard the interests of trial participants
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Provide approval for, and operate in, accordance with the specifications outlined in this DMC Charter
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Monitor the safety and efficacy of the trial intervention, through scheduled review of accumulating clinical data from the ongoing clinical trial and taking into account information from external sources
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Consider the need for additional unscheduled reviews of study data
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Review and evaluate the content of all unblinded data reports received
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Ensure the confidentiality of all information received relating to the trial
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In the event of further funding being required, to provide the Steering Committee and funder(s) with appropriate information and advice on the data gathered to date in a manner that will as far as possible protect the integrity of the study
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Participate in and vote on DMC recommendations, bearing in mind the fact that ethical considerations are of prime importance
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Make clear recommendations to the Steering Committee, with the Steering Committee Chair as the principal contact
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The DMC will review safety outcomes, including serious adverse events. Review of safety data should occur after 150, 300, 600, 900 and 1200 patients’ 6-month follow-up data. No formal boundaries will be used for terminating the study for safety reasons, but clear and consistent evidence of net harm that overrides any benefit should be apparent
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A formal interim analysis to assess efficacy will occur when approximately 67% of the planned primary efficacy events have accrued. The DMC may recommend early termination of the trial for overwhelming superiority of fluoxetine over control. A modified Haybittle-Peto monitoring boundary will be used as a guideline. If the primary efficacy comparison exceeds four standard errors in value, the DMC will initiate another interim analysis to be performed a minimum of 3 months later. If the monitoring boundary remains crossed, the DMC may recommend that the trial be terminated early for overwhelming superior efficacy of fluoxetine. No adjustment of the significance level for the final analysis is required.
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Chair DMC data review meetings
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Ensure that all relevant data have been reviewed by the DMC members and that all issues have been addressed
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Ensure that blinded individuals (i.e. the DMC coordinator, DMC contacts and DMC consultants) are not inappropriately exposed to confidential and/or unblinded data
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Ensure that only the members of the DMC are present during DMC deliberations, when DMC recommendations are discussed and DMC voting procedures are conducted
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Ensure the generation of confidential, written minutes of all closed sessions of any DMC Meetings and maintain these minutes as confidential to DMC members only, until the final (end of study) database lock is complete
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Ensure DMC approval of minutes of open and final sessions of all DMC meetings
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Communicate, author, sign and provide the official, final recommendations of the DMC within specified timelines and according to the specifications outlined in this charter. If the DMC is divided in opinion on any major issue affecting the DMC’s recommendation to the sponsor and EFFECTS Steering Committee, the DMC Chair is responsible for assembling and presenting the majority and dissenting opinions for all recommendations considered
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Arrange for consultation(s) and/or request additional data, as deemed necessary
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If deemed appropriate by the DMC, at appropriate intervals, arrange a teleconference meeting with the Chairs of the DMCs for the FOCUS (Professor Peter Langhorne) and AFFINITY (Professor Robert Herbert, Australia) trials. If necessary, to discuss accumulating data in strict confidence and any implications for the continuation of each of the trials. Each Chair may then subsequently need to consider whether to arrange a meeting of their respective trial DCM to discuss any issues that may arise from this liaison group
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Maintain a secure central file of all data outputs received for DMC review and all minutes of all sessions of DMC meetings. Provide a copy of this file to the sponsor, through the CI, once the final (end of study) database lock is complete