Table 3.

Understanding the various estimand strategies in diverse therapeutic areas

Estimand strategy	Measurement of interest
Treatment policy strategy – value of the outcome of interest regardless of the occurrence of the intercurrent event- the intention to treat analysis	Proportion of patients who achieved a goal of HbA1c <7% regardless of whether they took (or did not take) rescue medication[9] Therapeutic area: diabetes
Composite strategy – value of the variable with the intercurrent event being woven into the outcome variable	Proportion of patients with improvement in nasal polyps score of ≥1 point and completion of treatment period without surgery[13] Therapeutic area: nasal polyps
Hypothetical strategy – assumes that the intercurrent event did not happen in patients who were randomized	Proportion of patients who would achieve a goal of HbA1c <7% had they not taken rescue medication in a diabetes trial. Since patients in these studies are likely to take rescue medication, this value of <7% (in those who did take rescue medication) would be calculated using a specific statistical technique (modelling method) that is clearly stated in the estimand section of the protocol Therapeutic area: diabetes
Principal stratum strategy – measurement of the variable of interest is a subgroup of patients not likely to need rescue medication or not likely to discontinue treatment	Proportion of patients in a diabetes study (that includes both prediabetics and diabetics) who achieve a target HbA1c of <5.7%. If we look at the prediabetic patients (HbA1c between 5.7% and 6.4%) as a separate sub group, this group would be the one not likely to have needed rescue medication Therapeutic area: diabetes – this is a hypothetical example. Note that prediabetics are extremely unlikely to need rescue medication in any diabetes study
While on treatment strategy – measurements up until the time of the event particularly when the measurements are repeated at multiple time points	If patients of NASH are treated with a new intervention, serial liver biopsies are carried out at six monthly intervals to assess its effect. Fibrosis regression of at least two stages without worsening of NASH is the outcome of interest. If some of these patients are well controlled diabetics and their diabetes worsens while on treatment leading to medication discontinuation (with the new intervention), the results of the liver biopsies up until the discontinuation can be considered Therapeutic area: GI medicine – this is a hypothetical example

HbA1c=Glycated haemoglobin, GI=Gastrointestinal