Example

“6.2.1 Concomitant therapy

 

All medications, procedures, and significant non-drug therapies (including physical therapy and blood transfusions) administered after the participant was enrolled into the study must be recorded on the appropriate Case Report Forms.

 

Each concomitant drug must be individually assessed against all exclusion criteria/prohibited medication. If in doubt, the investigator should contact the Novartis medical monitor before randomizing a participant or allowing a new medication to be started. If the participant is already enrolled, contact Novartis to determine if the participant should continue participation in the study.

 

The patient must be told to notify the Treating Physician about any new medications that he/she takes after the start of canakinumab.

 

6.2.1.1 Permitted concomitant therapy requiring caution and/or action

 

Patients in this study will be enrolled to canakinumab or placebo, in addition to SOC per local practice, which may include anti-viral treatment, corticosteroids and supportive care.

 

Immunomodulator (topical or inhaled) use for asthma and atopic dermatitis or corticosteroid use (per medical judgement) are not restricted.

 

Use of oral, injected or implanted hormonal methods of contraception are allowed while on canakinumab.

 

6.2.2 Prohibited medication

 

The following medications are prohibited:

• Up to Day 29, concomitant use of biologics including anakinra, tocilizumab, abatacept, rilonacept, rituximab and any other biologics (investigational or marketed) and TNF inhibitors including etanercept, adalimumab, infliximab and/or other TNF inhibitors (investigational or marketed).

• All investigational medications being used in an investigational trial" [246]. 

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Explanation

 

In a randomised trial, a key goal is to have comparable study groups that differ only by the intervention being evaluated. Bias can arise when the trial groups receive different concomitant care, e.g., additional interventions that may impact trial outcomes [247]. 

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Trials may differ in what is meant by the “intervention being evaluated”. In some trials (with a marked explanatory approach), the “intervention” may be defined narrowly as the experimental intervention tested. In other trials (with a more pragmatic approach), the “intervention being evaluated” may be defined as the experimental intervention plus allowed concomitant interventions and procedures, e.g., rescue interventions. Also, in some multicentre trials, an intervention is added to “usual care”, which may differ considerably in content between centres (Item 15a).

 

Reviews of two samples of 108 and 292 trial protocols from 2016 found that 69% and 81% respectively reported the concomitant care that was permitted [9, 10]. 

 

The protocol should list the relevant concomitant care that is allowed (including rescue interventions) and prohibited during the conduct of the trial. “Relevant” concomitant care refers to concomitant care and interventions that could affect the trial outcome. Plans for recording any allowed and prohibited concomitant care during the trial should also be reported.

 

Summary of key elements to address

• Relevant concomitant care that is allowed (e.g., rescue interventions) or prohibited during the trial

• Any plans to record concomitant care received, including “usual care”