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Table 1 Case studies illustrating scenarios requiring causal estimation

From: A framework for the design, conduct and interpretation of randomised controlled trials in the presence of treatment changes

Causal estimation scenario

Case study

Treatment changes adjusted for

Causal question being addressed

Interest in efficacy despite pragmatic trial design

 

MRC hypertension trial

Addition of alternative treatments due to inadequate blood pressure control, or switches to alternative treatments due to side effects

Treatment efficacy in absence of treatment switches or additions

 

SANAD trial

Withdrawal from randomised treatment, addition of alternative treatments, or switches to alternative treatments due to inadequate seizure control

Treatment efficacy in absence of treatment changes due to inadequate seizure control

Trial protocol differs from practice

 

Vitamin A trial

Non-receipt of trial drug due to failure of the drug distribution system

Treatment efficacy among those who would have complied with active treatment if randomised to receive it

Contamination (control arm receives intervention)

 

Honey trial

More extreme forms of treatment, such as antibiotics, surgery or radiotherapy

Patient or clinician decision to switch from conventional dressings to honey

Treatment efficacy in absence of any treatment changes

 

PACIFICO trial

Switches from standard to new treatment on disease progression

Treatment efficacy in absence of treatment switches from standard to new treatment on progression

Interest in efficacy if taken as prescribed

 

Coronary Drug Project

Failure to take treatment according to prescribed schedule

Treatment efficacy among those who complied with treatment protocol

  1. MRC Medical Research Council, PACIFICO Purine-Alkylator Combination In Follicular lymphoma Immuno-Chemotherapy for Older patients, SANAD Standard and New Antiepileptic Drugs