Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
fatigue
SECONDARY
Analysis will be based on the intention-to-treat principle. However, in accordance with the TwiCs design, patients who are selected for the intervention arm may refuse the intervention. In case of a high refusal rate (i.e., > 15%), we will also conduct a per protocol (PP) analysis including patients who completed the treatment as allocated. However, refusal may be selective, e.g., patients who are less physically fit may refuse the intervention. As a result, PP analysis may under- or overestimate the treatment effect. We will also perform a complier average causal effect (CACE) analysis to estimate the treatment effect among “compliers,” i.e., patients that accepted and received the intervention offered compared with hypothetical control patients who, if offered the intervention, would have accepted.In the palliative oncology setting, questionnaire non-response is more likely due to inability to complete questionnaires as a result of for example fatigue and high distress or filling in questionnaires may be too burdensome. The proportion and patterns of missing data for the primary and secondary outcomes will be investigated. If needed, multiple imputation methods will be used to handle missing data under the assumption that data is missing at random. If the primary outcome data is determined to be missing not at random, a best–worst and worst-best case sensitivity analyses will be performed.