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64 Interventions in Alzheimer’s Disease KCE Reports 111
• presence of medial temporal lobe atrophy on MRI (MRI, of head: 459395,
459406)
• abnormal cerebrospinal fluid biomarkers (amyloid beta1-42, total tau, and
phospho-tau) (CSF, lumbar puncture procedure: 355493, 355504)
• a specific pattern on functional neuroimaging with 18F-FDG PET (PET:
442971, 442982, or functional scintigraphic test code used in case centre not
registered for PET exams: 442595, 442606) (SPECT technique did not meet
criteria for diagnostic accuracy)
• a proven AD autosomal dominant mutation within the immediate family
(DNA, genetic test: 588696, 588700)
4. The switch between ChEIs during the study period.
5. The time to discontinuation of ChEI treatment.
The median time between two prescriptions was computed, for patients having at least
two prescriptions. Multiple prescriptions on the same date were counted only once.
The methodology to compute the time to discontinuation of ChEls is similar to the one
used in the Ontario study. 129 However, we used a 30 day period as treatment period
after the last prescription (based on the median time between two prescriptions), and a
period of 170 days for drug renewal (and use of remaining medication). Patients without
subsequent prescription within 200 days were considered withdrawn from therapy (at
the date of last prescription + 30 days). Patients who died within this 200 days period
were considered censored for the analysis of time to discontinuation. So were patients
who received a last prescription within the 200 day period before the end of our study
period (31DEC2006). If there were more than 200 days between two prescriptions, the
patient was considered withdrawn from therapy (at the date of last prescription + 30
days), and was not included back in the study. Survival function was estimated with the
Kaplan Meier method. Differences in duration of treatment across patient’s
characteristics were also explored (type of medication, setting of first prescription).
6. The use of concomitant antipsychotics and antidepressants.
The use of antipsychotics and antidepressants was identified from the same databases as
those described above. The codes to identify these medications were those in
application in 2006. Setting of residence in 2006 (home or ROB/RVT-MR/MRS) was also
studied. The concomitant use was defined as any prescription of antipsychotics or
antidepressant between (and including) the first and last ChEl prescription date. No
treatment period was defined after date of prescription.
7. Survival after start of ChEI treatment.
The survival function after start of ChEl treatment was estimated with the Kaplan
Meyer method. The shape of the hazard function was estimated with the life table
method.
A Cox proportional hazard (PH) model was fitted to study the influences of some
patient’s covariates on the hazard function: age, sex, setting of first prescription
(hospital, ROB/RVT-MR/MRS, home), institutionalization after start of ChEl treatment,
use of concomitant antipsychotics (started before start of ChEl or after) and use of
concomitant antidepressants (started before start of ChEl or after). Some of these
covariates are defined after the start of ChEl treatment, and are therefore included as a
time-depended covariate in the Cox PH model. The assumption of proportional hazards
was tested for all covariates by including an interaction term time*covariate in the
model, and the model was adapted accordingly. Hazard ratios and 95% CI are
presented.