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| [ Print-friendly version ] |
| An assessment of the relative cost-effectiveness of different classes of drugs for Parkinson's disease (PD) |
| ISRCTN | ISRCTN69812316 |
| ClinicalTrials.gov identifier | |
| Public title | An assessment of the relative cost-effectiveness of different classes of drugs for Parkinson's disease (PD) |
| Scientific title | A large randomised assessment of the relative cost-effectiveness of different classes of drugs for Parkinson's disease (PD) |
| Acronym | PD MED |
| Serial number at source | HTA 98/03/02; Protocol Version 7.1 |
| Study hypothesis |
Clinical trials comparing different classes of Parkinson's disease drugs have been too small for reliable conclusions, have used inappropriate surrogate endpoints, and follow-up has been too short to evaluate long-term benefits and toxicity. This large (5000 patients), pragmatic, 'real-life' randomised trial addresses four fundamental, unanswered questions about PD treatment: what are the costs and benefits of: 1) Levodopa [LD]-sparing therapy (dopamine agonist [DA] or monoamine oxidase type B [MAOB] inhibitors) compared to LD alone in initial treatment; 2) DAs compared to MAOB inhibitors as initial LD-sparing therapy; 3) DAs compared to dopamine degradation inhibitors [DDIs] (catechol-O-methyltransferase [COMT] or MAOB inhibitors) when motor fluctuations develop on LD alone; 4) COMT inhibitors compared to MAOB inhibitors as DDI in advanced disease. Two separate 3-way randomisations allow classes of treatments for early and advanced disease to be investigated. Secondary objectives are to identify factors that might predict response to particular classes of drug and to provide a large collaborative framework within which other studies - in particular of neurosurgery and genetics - can be undertaken.
More details can be found at: http://www.hta.ac.uk/1119 Protocol can be found at: http://www.pdmed.bham.ac.uk/documents/PD_MED_Protocol_Version_6.1_Final_copy.pdf Please note that, as of 5th May 2009, the following amendments have been made to the public and scientific titles: 1. The public title was changed from "A large randomised assessment of the relative cost-effectiveness of different classes of drugs for Parkinson's disease (PD)" to "An assessment of the relative cost-effectiveness of different classes of drugs for Parkinson's disease (PD)" 2. The scientific title was added. Please note that, as of 16 January 2008, the anticipated end date of this trial has been updated from 31 October 2004 to 31 October 2011. Please note that as of 01/09/09, the target number of participants was updated from 5000 to 1500-2250. |
| Ethics approval | West Midlands REC, approved (subject to amendments) on 27/04/2000 (ref: MREC00/7/17). |
| Study design | Randomised controlled trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Parkinson's disease |
| Participants - inclusion criteria |
Current inclusion criteria as of 21/04/2009:
Patients are eligible for the early disease randomisation if: 1. They are newly or recently diagnosed with Parkinson's disease. It is important to ensure the accurate diagnosis of PD and the UK Brain Bank criteria should be used 2. They have functional disability requiring medical therapy. Patients not thought to require dopaminergic treatment at diagnosis may be entered once it is considered that such treatment becomes necessary 3. They are previously untreated for PD or have been treated with dopaminergic PD medication for less than 6 months 4. There is no definite contraindication to, or definite indication for, any of the therapies to which they might be allocated. (If it is considered that LD only is not an appropri ate option for a patient, they may be randomised two ways between DA and MAOBI. Similarly, if a MAOBI is not considered appropriate, a patient may be randomised two ways between LD and DA.) 5. They are able to complete the trial questionnaires. Non-English speaking patients may be entered if they have a carer, relative or other person who can help them fill in the questionnaires, or if translated documentation is available Patients are eligible for the later disease randomisation if: 1. They have PD and develop motor complications that are uncontrolled by LD (either alone or in combination with either a DA or a MAOBI) and hence require the addition of another class of drug 2. There is no definite contraindication to, or definite indication for, any of the therapies to which they might be allocated. (Patients who were already receiving a DA when uncontrolled motor fluctuations arose are not eligible for the DA arm and will be randomised between MAOBI and COMTI only. Patients who were receiving a MAOBI when uncontrolled motor fluctuations arose, or for whom the clinician does not wish a MAOBI to be an option, are not eligible for the MAOBI arm and will be randomised between DA and COMTI only.) 3. They are able to complete the trial questionnaires. Non-English speaking patients may be entered if they have a carer, relative or other person who can help them fill in the questionnaires, or if translated documentation is available. Previous inclusion criteria: Recently diagnosed patients with PD and patients with poorly controlled PD |
| Participants - exclusion criteria |
Added as of 21/04/2009:
Patients are not eligible for the early disease randomisation if: 1. They have received previous dopaminergic drug therapy for PD for more than 6 months 2. They are demented (as defined by the medical team responsible) 3. They are unable to give informed consent Patients are not eligible for the later disease randomisation if: 1. They are demented (as defined by the medical team responsible) 2. They are unable to give informed consent |
| Anticipated start date | 01/11/1999 |
| Anticipated end date | 31/10/2011 |
| Status of trial | Ongoing |
| Patient information material | Patient information sheet can be found at: http://www.pdmed.bham.ac.uk/documents/PDMEDPatient-info-sheet.pdf |
| Target number of participants | Added 01/09/09: 1500-2250 (1000-1500 and 500-750 in early and later disease respectively) |
| Interventions |
Current interventions as of 05/05/2009:
Early PD randomisation Patients with early PD are randomised between DA (+/- LD), MAOBI (+/- LD) and LD alone, with the option to omit either the MAOBI or LD alone arm. If treatment with either MAOBI or LD alone is considered to be definitely inappropriate for a particular patient, then this arm can be omitted. Later PD randomisation Those whose disease is no longer controlled by their first class of drug, after dose titration and/or addition of LD, are randomised between COMTI (+/- LD), MAOBI (+/- LD) and DA (+/- LD), with the option to omit either the MAOBI or the DA arm. Patients who were already receiving a DA when uncontrolled motor complications arose are not eligible for the DA arm but can be randomised between COMTI and MAOBI. Patients who were receiving a MAOBI when uncontrolled motor complications arose, or for whom the clinician considers that MAOBI treatment is definitely contraindicated, are not eligible for the MAOBI arm but can be randomised between COMTI and DA. N.B. Patients who have been entered into the early disease randomisation should be re-randomised into the later disease randomisation if motor complications develop that cannot be controlled by drug dose titration and/or addition of LD if on DA/MAOBI. Dosage The pragmatic 'real life' design of the trial allows clinicians to choose which DA, MAOBI and COMTI to use, and to vary the dose as they see fit. The eventual results will be more clinically relevant, in that drug usage will reflect normal clinical practice which involves frequent dose adjustments to achieve optimal symptom control. Open label treatment Blinding of treatment allocation is not considered necessary in PD MED because the potential for subjectively biased assessment is small. There is no reason to expect that patients will have any prior beliefs that one treatment will be better than another (all patients in both randomisations receive active therapy - there are no placebo arms). The duration of interventions will vary between individual participants. All participants will be followed up for at least 10 years (unless they die or withdraw from the trial). Previous interventions: New vs old drugs for PD |
| Primary outcome measure(s) |
Current primary outcome measures as of 21/04/2009:
1. Patient's self-evaluation of their functional status and quality of life (using the Parkinson's Disease Questionnaire 39 [PDQ-39]) 2. Cost-effectiveness (EuroQoL EQ-5D) All primary outcome measures will be assessed at baseline, 6 months and then at 1, 2, 3, 4 and 5 years. Previous primary outcome measures: PDQ-39 and EuroQol EQ-5D ( Activities of Daily Living and Quality of life), caregiver wellbeing, time to treatment failure, long-term toxicity, formal and informal care costs. A cost-minimisation (if no clinical difference) or cost-utility (cost/QALY) analysis will be undertaken. |
| Secondary outcome measure(s) |
Added as of 21/04/2009:
1. Cognitive function (Mini Mental State Examination [MMSE]), assessed at baseline and 5 years 2. Well being of carers (SF-36® Health Survey), assessed at baseline, 6 months and then at 1, 2, 3, 4 and 5 years 3. Resource usage, followed-up for 5 years 4. Toxicity and side-effects, including mortality rates, followed-up for 5 years 5. Time to onset of motor complications (early disease randomisation only) and time to surgical intervention or start of apomorphine (later disease randomisation only), followed-up for 5 years |
| Sources of funding | NIHR Health Technology Assessment Programme - HTA (UK) |
| Trial website | http://www.pdmed.bham.ac.uk/ |
| Publications | |
| Contact name | Prof Richard Gray |
| Address |
University of Birmingham Clinical Trials Unit
Robart Aitken Institute Division of Cancer Studies University of Birmingham |
| City/town | Birmingham |
| Zip/Postcode | B15 2TT |
| Country | United Kingdom |
| Tel | +44 (0)121 415 9100 |
| Fax | +44 (0)121 415 9135 |
| r.gray@bham.ac.uk | |
| Sponsor | University of Birmingham (UK) |
| Address | Edgbaston |
| City/town | Birmingham |
| Zip/Postcode | B15 2TT |
| Country | United Kingdom |
| Sponsor website: | http://www.bham.ac.uk/ |
| Date applied | 25/04/2003 |
| Last edited | 01/09/2009 |
| Date ISRCTN assigned | 25/04/2003 |
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