Table 2 Five trial management lessons learned from the CYCLE pilot RCT

1. Prepare and anticipate site needs

Initiation

Complete material preparation whilst waiting for approval to enrol participants. The Methods Centre prepared grant applications, case report forms, screening log templates, operations manuals, regulatory binders, training binders, training session slide decks, and other materials whilst applying for REB approval and negotiating institutional contracts at other sites. Preparatory work prevented later delays in the trial life cycle

Planning

Submit documents for REB and contracts as soon as possible at each site. In multicentre clinical trials, individual sites will require varying amounts of time to reach milestones. Be prepared to support sites with efficient systems by providing sample REB documents (e.g. protocols, consent forms). Aid sites by addressing questions and revisions quickly and completing as much trial preparation as possible whilst awaiting approvals

Planning

Select personnel with relevant experience and skill sets at each site to become team member early in the project life cycle

We engaged ICUs through the Canadian Critical Care Trials Group, and the research coordinators at these sites had experience screening and obtaining consent from ICU patients’ and/or their substitute decision makers. In our trial, screening for eligibility, obtaining informed consent, and randomization all had to occur within 4 days, a relatively short period of time from ICU admission. Obtaining informed consent from ICU patients’ substitute decision makers can be challenging [25]. The patient’s substitute decision maker may be uncertain of the patient’s wishes regarding research participation, have a limited understanding of research in critical care, and be anxious about research participation [25]

Training of frontline physical therapy clinicians comprised the majority of the CYCLE pilot RCT’s planning phase. We engaged physical therapy clinicians (physiotherapists, physiotherapist assistants/occupational therapist assistants) with experience assessing and treating similar patient populations to deliver the intervention and collect physical performance measures

Planning

Tailor training to individual site needs and experience levels. In the CYCLE pilot RCT, the ICU physiotherapists at Site 1 had cycling experience from a previous trial [26]; thus, they only received start-up training in the protocol, physical performance measurements, and research coordination. At other sites, we provided training on cycling, outcome measures, and study processes. New sites had opportunities to practice cycling and collecting physical outcome measures for at least 1 month before enrolling their first participant

Frontline clinician training should be planned sufficiently in advance to ensure that they are comfortable and competent with trial activities [5]. However, it should not occur so far in advance as to risk wasting time and financial resources on personnel who might not participate in the trial. We suggest prioritizing the training of key trial personnel (e.g. interventionists, research coordinators, lead outcomes assessors) who can act as trial champions. Trial champions can become trainers for new staff to optimize training efficiencies

Execution

Start data management early in the trial life cycle and anticipate data cleaning for at least 6 months after completing data collection

2. Communicate regularly with participating sites

Monitoring and controlling

Regular personalized communication between the central management team and site personnel is essential. Weekly communication allowed site personnel to notify the Methods Centre about trial challenges, such as staffing issues. As a result, the Methods Centre trained new personnel to minimize effects on recruitment and protocol adherence. Maintaining communication and a professional but personal relationship with trial personnel is challenging and requires significant time, but results in a more successful trial [5]

3. Proactively analyse and act on process measure data

Monitoring and controlling

Use screening logs to monitor clinical trial recruitment. From our screening log data, we identified a high consent rate but also had a high eligible non-randomized rate. Most eligible non-randomized patients were related to ICU physiotherapist capacity, suggesting that continuous recruitment depended on the availability of these frontline clinicians. The Methods Centre responded to this need by training additional personnel. We trained physiotherapists from other areas of the hospital and physiotherapist assistants/occupational therapist assistants to conduct physical performance measures to try to reduce the extra clinical responsibility of ICU physiotherapists

4. Develop contingency plans

Monitoring and controlling

Anticipate losing at least 10% recruitment time lost due to staffing gaps. Although our trial met its target sample size earlier than expected, we lost 13% of potential recruitment weeks due to leaves of absence, vacation, and staff turnover. Eligible participants could not be approached for consent without physiotherapist capacity to enrol and conduct the intervention. Our results suggest that both the number and availability of frontline therapists was an important factor in rehabilitation trials

Monitoring and controlling

Be prepared to train approximately one-third more trial personnel and allocate time and study budget to provide training sessions throughout the trial. We trained extra physiotherapists, physiotherapist assistants/occupational therapist assistants, research assistants, and research coordinators to replace personnel who changed roles and to account for staffing gaps

5. Express appreciation to participating sites

Execution

Express appreciation to frontline clinicians for their contributions. The CYCLE pilot RCT’s success relied on frontline clinicians dedicated to protocol fidelity for cycling and outcomes data. Clinicians added the trial activities to their usual workload. During the trial, we provided training certificates and recognized Canadian National Physiotherapy Month by offering therapists coffee gift cards. We acknowledged research coordinators, research assistants, ICU physiotherapists, and outcomes assessors in our publications. Recognizing the efforts of clinicians involved in the trial helps to ensure continued involvement and protocol adherence [5]