Dataset Information

A systematic review of biomarkers for disease progression in Parkinson's disease.

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.

SUBMITTER: McGhee DJ

PROVIDER: S-EPMC3637496 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Publications

A systematic review of biomarkers for disease progression in Parkinson's disease.

McGhee David J M DJ Royle Pamela L PL Thompson Paul A PA Wright David E DE Zajicek John P JP Counsell Carl E CE

BMC neurology 20130412

<h4>Background</h4>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.<h4>Methods</h4>MEDLINE and EMBASE (1950-2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting r ...[more]

PMID: 23587062

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Project description:BackgroundUsing surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true slowing of the neurodegenerative process. A systematic review was undertaken to determine what biomarkers for disease progression in Alzheimer's disease exist and how well they perform.MethodsMEDLINE and Embase (1950-2011) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with probable Alzheimer's disease diagnosed by formal criteria were included. We made no restriction on age, disease duration, or drug treatment. We only included studies with a longitudinal design, in which the putative biomarker and clinical measure were both measured at least twice, as this is the only appropriate study design to use when developing a disease progression biomarker. We included studies which attempted to draw associations between the changes over time in the biomarker used to investigate disease progression and a clinical measure of disease progression.ResultsFifty-nine studies were finally included. The commonest biomarker modality examined was brain MRI (17/59, 29% of included studies). Median follow-up in included studies was only 1.0 (IQR 0.8-1.7) year and most studies only measured the putative biomarker and clinical measure twice. Included studies were generally of poor quality with small numbers of participants (median 31 (IQR 17 to 64)), applied excessively restrictive study entry criteria, had flawed methodologies and conducted overly simplistic statistical analyses without adjusting for confounding factors.ConclusionsWe found insufficient evidence to recommend the use of any biomarker as an outcome measure for disease progression in Alzheimer's disease trials. However, further investigation into the efficacy of using MRI measurements of ventricular volume and whole brain volume appeared to be merited. A provisional 'roadmap' to improve the quality of future disease progression biomarker studies is presented.

Project description:BACKGROUND:Our understanding of the etiology, pathophysiology, phenotypic diversity, and progression of Parkinson's disease has stagnated. Consequently, patients do not receive the best care, leading to unnecessary disability, and to mounting costs for society. The Personalized Parkinson Project (PPP) proposes an unbiased approach to biomarker development with multiple biomarkers measured longitudinally. Our main aims are: (a) to perform a set of hypothesis-driven analyses on the comprehensive dataset, correlating established and novel biomarkers to the rate of disease progression and to treatment response; and (b) to create a widely accessible dataset for discovery of novel biomarkers and new targets for therapeutic interventions in Parkinson's disease. METHODS/DESIGN:This is a prospective, longitudinal, single-center cohort study. The cohort will comprise 650 persons with Parkinson's disease. The inclusion criteria are purposely broad: age???18?years; and disease duration ?5?years. Participants are followed for 2 years, with three annual assessments at the study center. Outcomes include a clinical assessment (including motor and neuro-psychological tests), collection of biospecimens (stool, whole blood, and cerebrospinal fluid), magnetic resonance imaging (both structural and functional), and ECG recordings (both 12-lead and Holter). Additionally, collection of physiological and environmental data in daily life over 2 years will be enabled through the Verily Study Watch. All data are stored with polymorphic encryptions and pseudonyms, to guarantee the participants' privacy on the one hand, and to enable data sharing on the other. The data and biospecimens will become available for scientists to address Parkinson's disease-related research questions. DISCUSSION:The PPP has several distinguishing elements: all assessments are done in a single center; inclusion of "real life" subjects; deep and repeated multi-dimensional phenotyping; and continuous monitoring with a wearable device for 2 years. Also, the PPP is powered by privacy and security by design, allowing for data sharing with scientists worldwide respecting participants' privacy. The data are expected to open the way for important new insights, including identification of biomarkers to predict differences in prognosis and treatment response between patients. Our long-term aim is to improve existing treatments, develop new therapeutic approaches, and offer Parkinson's disease patients a more personalized disease management approach. TRIAL REGISTRATION:Clinical Trials NCT03364894 . Registered December 6, 2017 (retrospectively registered).

Dataset Information

A systematic review of biomarkers for disease progression in Parkinson's disease.

Background

Methods

Results

Conclusion

Publications

A systematic review of biomarkers for disease progression in Parkinson's disease.

Similar Datasets

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