This trial was an embedded study within Efficacy oF Fluoxetine - a randomisEd Controlled Trial in Stroke (EFFECTS), an RCT of fluoxetine for stroke recovery . Briefly, EFFECTS included stroke patients 2-15 days after stroke from 35 centres in Sweden (28 acute stroke units, 5 rehabilitation centres and 2 geriatric rehabilitation centres). The primary objective of EFFECTS was to evaluate whether 20 mg fluoxetine would improve functional outcome at 6 months. Recruitment started 20 October 2014 and ended 28 June 2019, when the target of 1500 patients was met. The original recruitment goal was that each centre should randomise at least two patients per month, but as the study progressed, we discovered a huge discrepancy between centres; 7 out of 35 centres recruited half of the patients. This pattern, that a few centres have included the majority of subjects, was consistent during the trial. Although we managed to recruit about 30 patients per month, we noticed a certain decline in inclusion over time which could jeopardise funding. There was therefore an urgent need to improve recruitment into the trial
The EFFECTS trial included 1500 patients between 20th Oct 2014 and 28th June 2019 and had at most 35 centres. When ERUTECC started 9th Sep 2017, we had closed 6 centres for administrative reasons. Hence, there were 29 active centres in EFFECTS at the start of the intervention (Figure 1). We excluded the 5 top-recruiters (centres that recruited > 2 patients/months) since we believed that they had reached their full potential and the intervention would be too weak for them. Two centres were closed between randomisation and the intervention (administrative reasons), and two centres declined to participate, leaving 20 centres for the intervention (Figure 1).
*Insert Figure 1 here. File name: Figure 1 CONSORT flow diagram for the Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC) trial. ERUTECC is a randomised stepped wedge trial within the EFFECTS trial.pptx
We used a stepped wedge cluster design [14, 15], i.e., all centres received the intervention but at different times. By the end of the study, all participants had received the intervention, although the order in which participants receive the intervention was determined at random.
The 20 centres were divided into two categories: low and medium recruiters. We categorised the centres according to their average recruiting/month during an 18 months observation period between 1 March 2016 and 30 Aug 2017, into three levels: low (< 0.5 patients/month), medium (between 0.5-2.0 patients/month), and high recruiter (> 2 patients/month). The rationale for dividing centres into low- and medium recruiting was that we did not want to risk that all medium recruiting centres should fall into the same step, i.e. summer period, which is usually a low-recruiting period in Sweden. Another reason was that we suspected that the intervention might have different effects on low recruiters compared to medium centres. The statistician used stratified block randomisation in each group to allocate the 20 centres into 10 groups of two or three centres per step, leading to (at least) one medium and one low recruiting centre in each step. Because two centres were closed between randomisation and the intervention, two groups finally consisted of one centre. The time at which the centres started the intervention was randomly allocated. Every step consisted of 1-3 centres as shown in Figure 2.
**Insert Figure 2 here. File name: Figure 2. The ERUTECC stepped wedge trial design. M= medium recruiting centre and L= low recruiting centre. The yellow colour is two months before the intervention for each step, the blue colour is 60 days after the observation, and the red vertical bar indicates the time of the intervention.docx
Details of the teleconferences
Each centre was invited by email to the conference one month in advance (median 35 days). One week before the meeting an email with the attached agenda and a PowerPoint-presentation was sent to all participants (see Additional file 1). The meeting comprised a presentation of EFFECTS; background, rationale, aim and update of recruitment. The discussion was related to barriers to recruitment at the local site with study personnel and the head of department and what could be done to increase recruitment. Full details of the intervention can be found in the published ERUTECC protocol . To encourage recruitment, the Chief Investigator (EL) and the Trial Manager (EI) conducted the teleconference with the principal investigator and the trial team at each centre as well the head of department.
The centres estimated how many patients they assumed they could randomise in the future and formulated a commitment contract regarding goals for recruitment that was duly signed. Our hypothesis was that a commitment contract would make the personnel put more effort into the intervention.
Before starting the intervention, we had a run-in period during which we measured how many patients each centre recruited over a 60-day period. We chose 60 days because many centres recruited small numbers of patients, 0-1 patients/months, and we estimated that a shorter period would lead to overly small numbers, and random variations.
The primary outcome was the recruitment rate in the EFFECTS-trial 60 days post the ERUTECC intervention, compared with 60 days pre-intervention. Secondary outcomes were to compare the effect of the intervention on recruitment rates in:
1. Low- versus medium recruiting centres (according to their average recruiting/month in an 18 months observation period between 1 March 2016 and 30 Aug 2017)
2. Small versus large (>500 stroke/year) stroke units
3. Stroke units versus rehabilitation clinics
4. University hospitals versus non-university hospitals
5. Experienced centres versus non-experienced centres. (An experienced centre was defined as a centre where both the investigator and the study nurse had been involved in five or more trials or had carried out their own research).
6. Recruitment rate 61–120 days post teleconference compared with 61-120 days pre- intervention.
Exploratory, we compared the recruitment 30 day before with 30 days after the intervention (post-hoc analysis).
The participants were not informed about the aim of ERUTECC or that the timing of the intervention was randomised or that we measured numbers of randomised patients before and after intervention, but they were fully aware of the fact that we wanted to enhance recruitment. The exact numbers of recruitment per centre were available at the public domain through a link that was updated in real time since the start of the EFFECTS study .
For the primary outcome, we compared the numbers of included subjects 60 days before intervention with the numbers of subject 60 days post intervention. The null hypothesis was that there is no difference before and after. We considered a 20% increased recruitment rate as being a positive outcome. For the secondary outcomes, we compared the difference between the recruitment rates before and after intervention in the same way.