Case 1                                              

You are seeing a patient in the outpatient clinic. The patient was diagnosed with Alzeihmer's disease a couple of years ago. The family asks you about a new drug Donepezil and wants to know whether it will really help the patient. You promise to look into this and call the family next day.

What would be your answer?

Step 1. Formulating the question. In response to the family's question, you ask, "In a patient with Alzeihmer's disease would treatment with Donepezil as compared with placebo improve the functional disability?" (question on therapy)

Step 2. Identifying and retrieving relevant articles. You conduct a search in Medline using the searching term 'Donepezil.tw and Alzeihmer's disease.tw' and get 55 articles, scanning the first few reveals an article which seems to be very relevant to your question, "Donepezil improves cognition and global function in Alzheimer's disease. A 15-week double blind, placebo-controlled study" (Arch. Int. Med 158:1021, 1998)

Step 3. Appraising data critically. In the double blind, randomized-controlled, phase 3 trial involving 468 patients with mild to moderately severe Alzeihmer's disease treated with 5 mg and 10 mg doses of Donepezil, 32% of patients receiving 5 mg Donepezil (experimental event rate; EER1) and 38% of patients receiving 10 mg Donepezil (experimental event rate; EER₂) showed clinical improvement when compared to 18% improvement in the placebo group (control event rate; CER). The number needed to treat (NNT₁) for 5 mg for the duration of study 12 weeks was 7 (100 divided by 32-18), the NNT₂ for 10 mg of Donepezil was5 (100 divided by 38-18). The incidence of side effects was high in both the controls (69%) as well as the treatment group (68%-78%). Patients receiving 10 mg Donepezil had more GI side effects (nausea, vomiting diarrhea).

Step 4. Applying the evidence. You look in your records and try to establish the severity of Alzeihmer's in your patient. You realize that the study results can not be applied to patients with advanced Alzeihmer's disease. You explain the clinical significance to the family using the calculated NNT. You instruct them that despite improvement of symptoms there was no benefit in survival of patients who took Donepezil. Also a large group of these patients developed some GI side effects. You instruct the family that drugs that cure disease or have dramatic benefits are straightforward, and the results are easy to interpret. However, the evaluation of treatments designed to slow the gradual decline that occurs in patients with Alzeihmer's maybe more difficult to interpret.

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