Page 15 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

Loss to follow-up was defined as the number of persons randomized who did not reach the endpoint of

20
the study, independent of the reason and the use of ITT analysis. We adopted an overall loss to follow-
up of 40% as a cut-off point for poor quality.

We rated trials that had a fatal flaw in one or more categories as poor quality; we did not include them in
this analysis. We rated trials that met all criteria as good quality. The majority of trials received a quality

rating of fair. This includes studies that presumably fulfilled all quality criteria but did not report their
methodologies to an extent that answered all our questions. Thus, the “fair quality” category includes
trials with quite different strengths and weaknesses and a range of validity.

The last observation carried forward (LOCF) method of data analysis is a particular issue in Alzheimer’s

disease. The reason is that the natural course of the disease leads to a gradual decline in cognition and
daily functioning over time. Particularly in longer studies measurements carried forward can bias results
towards an overestimation of the treatment effect. We took this potential bias into consideration when we

appraised each study and highlighted possible bias in the text whenever appropriate.

Alzheimer's Drugs Page 15 of 205