Analysis populations efficacy

The ITT analysis population and the per-protocol (efficacy or evaluable) population are typically used in efficacy analyses. As described in the previous chapter, the ITT population comprises all subjects in a clinical trial that were randomized to a treatment group, regardless if any data were actually collected from them. 

Module HI Presents the detailed efficacy findings including the intent-to-treat analysis population and the efficacy data listings. 

Both the ITT and the safety populations can be used in the analysis of safety data. The ITT and per-protocol population are typically used in the analysis of efficacy data. 

Observational studies STRIDE-2X is the 1-year open extension study of the 18 week STRIDE-2 (Sitaxsentan To Relieve ImpaireD Exercise) investigation that followed patients taking sitaxsentan or bosentan for pulmonary artery hypertension [87 ]. As well as efficacy measures, the researchers included time to withdrawal because of adverse events and time to rises in hepatic aminotransferases in the outcome measures. For the analysis population, the risk of raised aminotransferases to more than 3 times the upper limit of normal at 1 year was 6% with sitaxsentan 100 mg/day and 14% with bosentan. The cumulative risk of withdrawal at 1 year with raised aminotransferases was 3% with sitaxsentan 100 mg/day and 9% with bosentan. Other adverse events were peripheral edema, nasopharyngitis, dyspnea, and cough, consistent with previous trials in pulmonary artery hypertension. The overall withdrawal rates at 1 year were 15% with sitaxsentan 100 mg/ day and 30% with bosentan. Sitaxsentan therefore seems to have similar efficacy to bosentan and from this evidence may have the advantage of causing fewer hepatic adverse events in longer-term treatment (but see below). 

Kranzler HR, Van Kirk J Efficacy of naltrexone and acamprosate for alcoholism treatment a meta-analysis. Alcohol Clin Exp Res 23 1335-1341, 2001 Kranzler HR, Babor TF, Lauerman R Problems associated with average alcohol consumption and frequency of intoxication in a medical population. Alcohol Clin Exp Res 14 119-126, 1990... 

When attempting to demonstrate the efficacy of a new drug, the use of data that do not favor this desired outcome is deemed appropriate. Then, if there is compelling evidence of the drug s efficacy, this evidence will be particularly noteworthy. This is the case for the ITT population. Analysis of the ITT population data may also provide estimates of treatment effects that are more likely to mirror those observed in subsequent clinical practice, i.e., the treatment of patients in real-world settings, should the drug subsequently be approved for marketing. 

In contrast to the conservative ITT analysis, analysis of the per-protocol population may maximize the opportunity to demonstrate efficacy the per-protocol population is the population in which the treatment is likely to perform best. Adherence to the protocol may be related to the treatment and outcome (Kay, 2005). This is why the per-protocol analysis is considered secondary to the more conservative ITT analysis. 

Piotrovsky, V. Drug efficacy analysis as an exercise in dynamic (indirect-response) population PK-PD modelling. Population Approach Group... 

An analysis of responses in subsets of the overall population is required. The extent of this part of the integrated summary of efficacy will depend to a large extent on the drug and its intended patient population. Subsets of interest may include sex, race, age, disease severity, concomitant illness, concomitant drugs, smoking and alcoholism, and prior therapy. 

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