TY - JOUR

T1 - Patient preferences for outcomes in clinical trials: implications for medicines optimization

AU - Holmes, Emily

AU - Marson, A.G.

AU - Hughes, Dyfrig

PY - 2017/5/8

Y1 - 2017/5/8

N2 - BackgroundDrug choices for given therapeutic indications are often guided byclinical trial evidence, however, patients may consider outcomesbeyond those measured as primary endpoints within trials in theirdecision to adhere to medication. Discrete choice experiments (DCEs)are a valid method that has been used to quantify patient preferencesfor drug outcomes. Data from DCEs may be combined withthe results of clinical trials to provide a more patient-orientated perspectiveon drug choice.ObjectiveTo demonstrate the impact of incorporating patients’ benefit-riskpreferences into the results of clinical trials, using a case study ofpreferences for anti-epileptic drugs (AEDs).MethodsPreference weights for outcomes of AEDs (12-month remission, fewerseizures, depression, memory problems, aggression, foetal abnormality)were derived from a web-based DCEs of 414 adult patients withepilepsy. Rates for each of these outcomes were extracted from alarge randomised controlled trial comparing the effectiveness of newand standard AEDs (SANAD), and from a systematic review of treatmentsof epilepsy in pregnancy. The preference weights were combinedwith the clinical event rates to estimate of patient utility foreach AED. The probability of patients preferring each AED was thencalculated as the ratio of exponentiation of the utility of each individualAED to the sum of the exponentiation of the utilities of all AEDs.Results were compared to rankings of AEDs as indicated by clinicaltrials.ResultsThe rank order of AEDs based on trial data for remission: lamotrigine,carbamazepine, topiramate, oxcarbazepine, then gabapentin, changedwhen patient benefit-risk preference was considered. The probabilityof patients with partial epilepsy preferring each AEDs was, indescending order: carbamazepine (0.29), lamotrigine (0.26), oxcarbazepine(0.24), gabapentin (0.15), topiramate (0.07). Women with thepotential 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 patientswith generalised or unclassified epilepsy. Changes to rank orderingare explained by patients’ stronger preferences for reducing the riskof AEs than for improving treatment benefit. In return for a 1% improvementin 12-month remission, the maximum acceptable risk ofadverse events was: depression 0.31%, memory problems 0.30%, aggression0.25%. The maximum acceptable risk of adverse event in exchangefor a 1% improvement in 12-remission was, for women withthe potential to become pregnant was: depression 0.56%, memoryproblems 0.34%, and foetal abnormality 0.20%.ConclusionsDCEs represent a robust method for quantifying benefit-risk preferencesthat can be analysed alongside clinical trial data, to provide apatient-orientated perspective on the optimal choice of treatment.

AB - BackgroundDrug choices for given therapeutic indications are often guided byclinical trial evidence, however, patients may consider outcomesbeyond those measured as primary endpoints within trials in theirdecision to adhere to medication. Discrete choice experiments (DCEs)are a valid method that has been used to quantify patient preferencesfor drug outcomes. Data from DCEs may be combined withthe results of clinical trials to provide a more patient-orientated perspectiveon drug choice.ObjectiveTo demonstrate the impact of incorporating patients’ benefit-riskpreferences into the results of clinical trials, using a case study ofpreferences for anti-epileptic drugs (AEDs).MethodsPreference weights for outcomes of AEDs (12-month remission, fewerseizures, depression, memory problems, aggression, foetal abnormality)were derived from a web-based DCEs of 414 adult patients withepilepsy. Rates for each of these outcomes were extracted from alarge randomised controlled trial comparing the effectiveness of newand standard AEDs (SANAD), and from a systematic review of treatmentsof epilepsy in pregnancy. The preference weights were combinedwith the clinical event rates to estimate of patient utility foreach AED. The probability of patients preferring each AED was thencalculated as the ratio of exponentiation of the utility of each individualAED to the sum of the exponentiation of the utilities of all AEDs.Results were compared to rankings of AEDs as indicated by clinicaltrials.ResultsThe rank order of AEDs based on trial data for remission: lamotrigine,carbamazepine, topiramate, oxcarbazepine, then gabapentin, changedwhen patient benefit-risk preference was considered. The probabilityof patients with partial epilepsy preferring each AEDs was, indescending order: carbamazepine (0.29), lamotrigine (0.26), oxcarbazepine(0.24), gabapentin (0.15), topiramate (0.07). Women with thepotential 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 patientswith generalised or unclassified epilepsy. Changes to rank orderingare explained by patients’ stronger preferences for reducing the riskof AEs than for improving treatment benefit. In return for a 1% improvementin 12-month remission, the maximum acceptable risk ofadverse events was: depression 0.31%, memory problems 0.30%, aggression0.25%. The maximum acceptable risk of adverse event in exchangefor a 1% improvement in 12-remission was, for women withthe potential to become pregnant was: depression 0.56%, memoryproblems 0.34%, and foetal abnormality 0.20%.ConclusionsDCEs represent a robust method for quantifying benefit-risk preferencesthat can be analysed alongside clinical trial data, to provide apatient-orientated perspective on the optimal choice of treatment.

U2 - 10.1186/s13063-017-1902-y

DO - 10.1186/s13063-017-1902-y

M3 - Meeting Abstract

VL - 18 (Suppl 1)

SP - 192

JO - Trials

JF - Trials

SN - 1745-6215

IS - O18

T2 - 4th International Clinical Trials Methodology Conference (ICTMC) and the 38th Annual Meeting of the Society for Clinical Trials

Y2 - 7 May 2017 through 10 May 2017

ER -