Patient preferences for outcomes in clinical trials: implications for medicines optimization

Background
Drug choices for given therapeutic indications are often guided by
clinical trial evidence, however, patients may consider outcomes
beyond those measured as primary endpoints within trials in their
decision to adhere to medication. Discrete choice experiments (DCEs)
are a valid method that has been used to quantify patient preferences
for drug outcomes. Data from DCEs may be combined with
the results of clinical trials to provide a more patient-orientated perspective
on drug choice.
Objective
To demonstrate the impact of incorporating patients’ benefit-risk
preferences into the results of clinical trials, using a case study of
preferences for anti-epileptic drugs (AEDs).
Methods
Preference weights for outcomes of AEDs (12-month remission, fewer
seizures, depression, memory problems, aggression, foetal abnormality)
were derived from a web-based DCEs of 414 adult patients with
epilepsy. Rates for each of these outcomes were extracted from a
large randomised controlled trial comparing the effectiveness of new
and standard AEDs (SANAD), and from a systematic review of treatments
of epilepsy in pregnancy. The preference weights were combined
with the clinical event rates to estimate of patient utility for
each AED. The probability of patients preferring each AED was then
calculated as the ratio of exponentiation of the utility of each individual
AED to the sum of the exponentiation of the utilities of all AEDs.
Results were compared to rankings of AEDs as indicated by clinical
trials.
Results
The rank order of AEDs based on trial data for remission: lamotrigine,
carbamazepine, topiramate, oxcarbazepine, then gabapentin, changed
when patient benefit-risk preference was considered. The probability
of patients with partial epilepsy preferring each AEDs was, in
descending order: carbamazepine (0.29), lamotrigine (0.26), oxcarbazepine
(0.24), gabapentin (0.15), topiramate (0.07). Women with the
potential to become pregnant, had a preference probability of: lamotrigine
(0.31), oxcarbazepine (0.21), gabapentin (0.20), carbamazepine
(0.19), topiramate (0.09). Comparable results were found for patients
with generalised or unclassified epilepsy. Changes to rank ordering
are explained by patients’ stronger preferences for reducing the risk
of AEs than for improving treatment benefit. In return for a 1% improvement
in 12-month remission, the maximum acceptable risk of
adverse events was: depression 0.31%, memory problems 0.30%, aggression
0.25%. The maximum acceptable risk of adverse event in exchange
for a 1% improvement in 12-remission was, for women with
the potential to become pregnant was: depression 0.56%, memory
problems 0.34%, and foetal abnormality 0.20%.
Conclusions
DCEs represent a robust method for quantifying benefit-risk preferences
that can be analysed alongside clinical trial data, to provide a
patient-orientated perspective on the optimal choice of treatment.