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)

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 forthe 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should provide a description of each treatment, an explanation of the order in which the treatments are introduced or withdrawn, and the triggers for their introduction, where applicable.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 interventiongroup 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.

Box 2 Examples of essential information to be reported for various types of interventionsa

Intervention

Essential information to be reported

Drug(24)

● generic name

● manufacturer

● dose

● route of administration (e.g., oral,   intravenous)

● timing

● titration regimen if applicable

● duration of administration

● procedure for tailoring the intervention   to individual participants

● conditions under which interventions   will be withheld

● whether and how adherence of patients to   the intervention will be assessed or enhanced

● any physical or informational materials   used in the intervention and where the materials can be accessed

Rehabilitation, behavioural treatment, education, or   psychotherapy(222)

Qualitative information

● theory/rationale for essential   intervention elements

● content of each session

● mode of delivery (individual / group,   face to face / remote)

● whether the treatment is supervised

● the content of the information exchanged   with participants

● the materials used to give information

● procedure for tailoring the intervention   to individual participants

● whether and how the interventions will   be standardised

● background and expertise of individuals   delivering the interventions

● whether and how adherence of individuals   delivering the interventions to the protocol will be assessed or enhanced

● whether and how adherence of patients to   the intervention protocol will be assessed or enhanced

● any physical or informational materials   used in the intervention and where the materials can be accessed

Quantitative information

● intensity of intervention where   appropriate

● number of sessions

● session schedule

● session duration

● duration of each main component of each   session

overall   duration of the intervention

Surgery, technical procedure, or implantable devices(222)

● preoperative care relevant details

● intraoperative care relevant details

● configuration of any device

● postoperative care relevant details

● procedure for tailoring the intervention   to individual participants

● whether and how the interventions will   be standardised

● background and expertise of individuals   delivering the interventions

● whether and how adherence of individuals   delivering the interventions to the protocol will be assessed or enhanced

● any physical or informational materials   used in the intervention and where the materials can be accessed

aThis list is not intended to be exhaustive; it is a starting point for authors to consider when reporting the intervention. Information inspired from(24, 222)

Summary of key elements to address

● Details of each intervention and comparator to allow replication, including:

o Components of the intervention and comparator

o How they will be administered

o When and for how long they will be administered

o Any procedure for tailoring the intervention to individual participants

o Any physical or informational materials to be used as part of the intervention/comparator (e.g., instruction manual) and where the materials will be made accessible

● When comparator group is “usual care”:

o Description of usual care, and any plans to track and measure it during the trial

o Whether the intervention group will also receive usual care