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Open Access Highly Accessed Research article

A systematic review of biomarkers for disease progression in Parkinson’s disease

David JM McGhee1*, Pamela L Royle2, Paul A Thompson3, David E Wright3, John P Zajicek4 and Carl E Counsell1

Author Affiliations

1 Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UK

2 Division of Health Sciences, University of Warwick, Coventry, CV4 7AL, UK

3 Centre for Health and Environmental Statistics, Plymouth University, ITTC Building, Tamar Science Park, Plymouth, PL6 8BX, UK

4 Clinical Neurology Research Group, Peninsula College of Medicine and Dentistry, University of Plymouth, Tamar Science Park, Plymouth, PL6 8BX, UK

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BMC Neurology 2013, 13:35  doi:10.1186/1471-2377-13-35

Published: 12 April 2013

Abstract

Background

Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson’s disease (PD) exist.

Methods

MEDLINE and EMBASE (1950–2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came.

Results

183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality - cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses.

Conclusion

We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional ‘roadmap’ for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.

Keywords:
Parkinson disease; Biomarkers; Disease progression; Clinical trials; Neuroprotective agents