PDMED: Parkinson's Disease Medicines trial
A large randomised assessment of the relative cost-effectiveness of classes of drugs for Parkinson's disease.
|Dates:||ongoing since 1998|
|Funding:||NHS Health Technology Assessment Programme|
|Collaborators:||Clinical Trials Unit, University of Birmingham|
Parkinson’s disease (PD) is one of the commonest causes of disability in older people with at least 8,000 new cases diagnosed each year in the UK alone. Levodopa (LD) controls symptoms for most patients but long-term use is associated with motor complications. A number of other drugs have been used, either alone or with reduced doses of LD, in an attempt to delay the onset of motor complications, or to control complications in later disease once they have developed. These agents have primarily been from three classes of drug: dopamine agonists (DA), monoamine oxidase type B inhibitors (MAOBI), catechol-O-methyltransferase inhibitors (COMTI).
All of these drugs are beneficial when used alone, but there remains uncertainty about their relative effectiveness. One reason for this is that previous comparative studies included too few patients, and most had inadequately short follow-up. A second problem is that the main outcome measures used in previous studies have been clinician-rated assessments of motor impairments and disability, which fail to assess the impact of the disease on the whole patient. For example, a recent agonist trial demonstrated a delay in time to onset of motor complications with DA, but at the expense of poorer control of the symptoms of PD, and an increase in hallucinations. Depression, dementia and sleep disturbance are other common problems that may be more important for patients and carers than motor complications. Another uncertainty is the role of the MAOBI, selegeline, which may be neuroprotective but was reported to increase mortality in one trial - although this has not been confirmed in other studies. DAs and COMTIs are considerably more expensive than either LD or selegiline and better evidence is needed on the balance of benefits and risks of these drugs to establish their cost-effectiveness.
PD MED is a large, simple, "real-life" trial that aims to determine much more reliably which class of drugs provides the most effective control, with the fewest side-effects, for both early and later PD. Patients with early PD are randomised between DA, MAOBI and LD alone, with the option to omit either the MAOBI or LD alone arm. Those with later PD are randomised between COMTI, DA and MAOBI, with the option to omit either the DA or the MAOBI arm. The main outcome measure is patient-rated quality of life, using the PDQ-39 scale, which assesses all aspects of the patient’s life, and is sensitive to changes considered important to patients but not identified by clinical ratings. By September 2008 the trial had recruited nearly 1800 patients.
The economic evaluation being carried out alongside the trial is collecting information on the costs as well as the effectiveness of the alternative interventions. The economic analysis will reflect the fundamental trial questions, namely: for early PD, how cost-effective is DA +/- LD, or MAOBI +/- LD, in comparison with LD alone? And for advanced PD, how cost effective is MAOBI (+ LD), or COMTI (+LD), in comparison with DA (+LD)? The primary outcome measures of the trial are quality of life, self-assessed by the EuroQol EQ-5D utility measure, and effectiveness, self-assessed by the PDQ-39. Hence the cost-effectiveness measures will be the cost per quality adjusted life year (QALY) gained, or the cost per 1-point change in the mobility scale of the PDQ-39.
The economic evaluation being carried out alongside the trial is collecting information on the costs as well as the effectiveness of the alternative interventions. The economic analysis will reflect the fundamental trial questions, namely: for early PD, how cost-effective is DA +/- LD, or MAOBI +/- LD, in comparison with LD alone? And for advanced PD, how cost effective is MAOBI (+ LD), or COMTI (+LD), in comparison with DA (+LD)? The primary outcome measures of the trial are quality of life, self-assessed by the EuroQol EQ-5D utility measure and effectiveness, self-assessed by the PDQ-39. So cost-effectiveness could be: the cost per quality adjusted life year (QALY) gained, or the cost per 1-point change in the mobility scale of the PDQ-39.
Recall periods for health and social service resource utilisation
For all patient-specific resource-use events, the selection of the recall interval is important in order to minimise recall bias in the estimates of resource use. By comparing recall of resource use over the periods 12 months, 6 months or 3 months it is hoped this will inform the PDMED economic evaluation of the best interval for recall, hence providing the most accurate resource use data with which to compare the arms of the trial. In addition, this study will also inform future economic evaluations of the optimal period of recall or provide information as to the estimated scale of error so that adjustments can be made to future studies. This is a sub-study of the economic evaluation built into the PDMED trial.