Example

 

“(…) Azithromycin, or Zithromax, is supplied as an oral suspension in bottles containing azithromycin dehydrate powder equivalent to 1200 mg per bottle and the following inactive ingredients: sucrose, tribasic anhydrous sodium phosphate, hydroxypropyl cellulose, xanthan gum; FD&C Red #40, and flavoring including spray dried artificial cherry, crème de vanilla, and banana. After constitution, a 5 mL suspension contains 200 mg of azithromycin. This study will utilize the European Union formulation of the drug, which is comparable to the United States formulation.

 

Azithromycin and placebo will be administered as a single oral 1.2 g dose. (…) We propose providing a 1.2 gm oral dose depending on immediate availability and formulation for azithromycin and placebo. (…)

 

The comparator group for this trial will be a masked placebo. We propose to use placebo due to the lack of safety and efficacy data for azithromycin [227]. 

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“The Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together [SPIN-CHAT] Program is a brief group videoconference intervention that was developed based on best-practice principles for managing anxiety and worry [references] recommendations for maintaining mental health during COVID-19 [references] and input from the SPIN COVID-19 Patient Advisory Team. The intervention will be delivered 3 times per week for 4 weeks during the COVID-19 crisis in 60- to 90-min sessions. Each session will include 3 segments: (1) engagement via therapeutic recreation activities (20–30 min); (2) education on information management and anxiety management through psychological and other strategies (20–30 min); and (3) open discussion and social support (20–30 min). Each intervention group will be moderated by a member of the research team or by leaders who have been trained in our SPIN support group leader training program [references] .The moderators will support participants to develop routines ... Supervision and support of group moderators will be provided by a trained social worker with 28 years of total experience and over ten years of experience working with the systemic sclerosis [SSc] community. Educational segments in each session will be delivered by a research team member with experience and training related to the topic.

 

Leisure activities that will be done at the start of each session will include games (e.g., Pictionary, charades, pub-style trivia), creative activities (e.g., roll-a-story, where participants roll a dice ...), …

 

There will be an initial program overview in the first session. Then, educational segment topics will include (1) healthy information management and social connection (session 2); (2) managing worry (sessions 3, 7, 11); (3) ...

 

In the healthy information management and social connection segment, strategies will be provided and discussion will be facilitated on how to stay informed via accurate information sources while avoiding sensationalist ...

 

The managing worry segments will include an overview of worry, including what it is, the difference between helpful and harmful anxiety or worry, how to identify triggers of worry, and strategies to manage worry, … Exercises will be done with the group to illustrate techniques. In the relaxation segments, an introduction to the purpose of relaxation techniques … Adaptations for participants with breathing or positioning limitations will be made.

 

The physical activity segments will include an overview of the physical and psychosocial benefits of physical activity for maintenance of health for chronic disease management, [references] including ... Participants will be guided through movement options for the home-based setting, including warm-ups, aerobic, and strength activities. Behaviour change techniques to foster building the habit of moving more at home will be taught, including goal-setting, scheduling, addressing barriers, and building social support.[references]

 

Activity engagement sessions will be guided by the leisure education content model.[reference] Sessions will involve interactive group discussion about the benefits of leisure engagement [reference] ... Sessions will explore barriers to leisure for persons with SSc and include tips for finding leisure resources within the participants' own homes, both in-person and online.

 

Based on our previous experience [references] and consistent with previous trials of videoconference training,[references] 8 participants will be assigned to each training group to maximize effective interaction and participation. Sessions will be delivered using the GoToMeeting® videoconferencing platform, a high-performance platform that has been used successfully in similar applications [references] and in feasibility and full-scale trials of SPIN's support group leader training program.[references]

(…)

 

Participants assigned to the waitlist will receive notices and reminders to complete trial measures as part of the SPIN-COVID-19 Cohort. They will be contacted with information on intervention groups post-trial [228].

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“Usual care is defined as ‘the wide range of care that is provided in a community whether it is adequate or not, without a normative judgment’ [reference]. To increase external validity and relevance of study findings to clinical practice, the study protocol does not restrict access to usual care, in line with our pragmatic study design [reference] and the possibility for heterogeneity of usual care treatments available for older people with frailty. For example, usual care at a personal level will depend on individual frailty, level of independence and social predicaments. It is likely to include GP [general practitioner] care, district nurse input, and home care packages, but usual care may also include the use of voluntary sector services, day centres, and respite care. Use of and referral to services (including other rehabilitation) will be recorded at baseline and follow-up assessments in both intervention and control groups [229].

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Explanation

 

The protocol’s description of the essential characteristics of the trial intervention and comparator are important for correct implementation during the trial, but are also important for healthcare providers, systematic reviewers, policymakers, and others who are interested in understanding, implementing, or evaluating the intervention [230]. 

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This principle applies to all types of interventions, but is particularly true for complex interventions (e.g., health service delivery), which consist of interconnected components that can vary between healthcare providers and settings.

 

Reviews of two samples of 108 and 292 trial protocols from 2016 found that key elements of pharmacologic treatments (i.e., generic name, dose, and schedule of intervention) were reported in more than 90% of protocols [9, 10].

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Protocols should provide a comprehensive description of each intervention and comparator, including usual care or placebo as applicable. Key information includes the different components of the intervention/comparator; how, when, and for how long it will be administered; the intervention material (i.e., any physical or informational materials used for the intervention/comparator (e.g., instruction manual), including those provided to participants or used in intervention delivery or in training of intervention providers and where it can be accessed (e.g., online appendix, URL); and the procedure for tailoring the intervention/comparator to individual participants (Box 2). 

 

If the comparator or intervention group is to receive a combination of treatments, the authors should provide a description of each treatment, an explanation of the order in which the treatments are introduced or withdrawn, and the triggers for their introduction, where applicable.

 

Interventions that consist of ”usual care” (also called ”standard of care”) require further elaboration in the protocol, as this care can vary substantially across sites and patients, as well as over the duration of the trial. Further, it is important to clarify whether the intervention group also receives usual care and what will actually differ between the groups.

 

Specific guidance has been developed to improve the reporting of interventions, particularly the Template for Intervention Description and Replication – TIDieR, [24] TIDieR-Placebo, [231] which applies to trial protocols (as well as trial reports). The CONSORT extensions for nonpharmacologic treatments [222] were developed for trial reports, but may also inspire authors of trial protocols.