Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2013

Open Access 01-12-2013 | Research article

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

Authors: David JM McGhee, Pamela L Royle, Paul A Thompson, David E Wright, John P Zajicek, Carl E Counsell

Published in: BMC Neurology | Issue 1/2013

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Twelves D, Perkins KS, Counsell C: Systematic review of incidence studies of Parkinson's disease. Mov Disord. 2003, 18 (1): 19-31. 10.1002/mds.10305.CrossRefPubMed
2.
Clarke CE: A "cure" for Parkinson's disease: can neuroprotection be proven with current trial designs?. Mov Disord. 2004, 19 (5): 491-498. 10.1002/mds.20057.CrossRefPubMed
3.
Rascol O: "Disease-modification" trials in Parkinson disease: target populations, endpoints and study design. Neurology. 2009, 72 (Suppl 7): S51-S58.CrossRefPubMed
4.
Clarke CE: Are delayed-start design trials to show neuroprotection in Parkinson's disease fundamentally flawed?. Mov Disord. 2008, 23 (6): 784-789. 10.1002/mds.21918.CrossRefPubMed
5.
Temple RJ: A regulatory authority's opinion about surrogate endpoints. Clinical Measurement in Drug Evaluation. Edited by: Nimmo WS, Tucker GT. 1995, New York: J. Wiley
6.
Biomarkers Definitions Working Group: Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001, 69 (3): 89-95.CrossRef
7.
Consensus report of the Working Group on: "Molecular and Biochemical Markers of Alzheimer's Disease": The Ronald and Nancy Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging Working Group. Neurobiol Aging. 1998, 19 (2): 109-116.CrossRef
8.
Brooks DJ, Frey KA, Marek KL, Oakes D, Paty D, Prentice R, Shults CW, Stoessl AJ: Assessment of neuroimaging techniques as biomarkers of the progression of Parkinson's disease. Exp Neurol. 2003, 184 (Suppl 1): S68-S79.CrossRefPubMed
9.
Hughes AJ, Daniel SE, Kilford L, Lees AJ: Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992, 55 (3): 181-184. 10.1136/jnnp.55.3.181.CrossRefPubMedPubMedCentral
10.
Gelb DJ, Oliver E, Gilman S: Diagnostic criteria for Parkinson disease. Arch Neurol. 1999, 56 (1): 33-39. 10.1001/archneur.56.1.33.CrossRefPubMed
11.
Calne DB, Snow BJ, Lee C: Criteria for diagnosing Parkinson's disease. Ann Neurol. 1992, 32 (Suppl 1): S125-S127.CrossRefPubMed
12.
Weiner WJ, Lang AE: Parkinson's disease. Movement Disorders, A comprehensive survey. Edited by: Weiner WJ, Lang AE. 1989, Mount Kisco, New York: Futura Publishing, 23-115.
13.
Fahn S, Eton RL: UPDRS Development Committee: The Unified Parkinson's Disease Rating Scale. Recent Developments in Parkinson's Disease Volume 2. Edited by: Fahn S, Marsden CD, Goldstein M, Calne DB. 1987, Florham Park, New Jersey: Macmillan Healthcare Information, 153-163.
14.
Folstein MF, Folstein SE, McHugh PR: "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975, 12 (3): 189-198. 10.1016/0022-3956(75)90026-6.CrossRefPubMed
15.
Roth M, Tym E, Mountjoy CQ, Huppert FA, Hendrie H, Verma S, Goddard R: CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry. 1986, 149: 698-709. 10.1192/bjp.149.6.698.CrossRefPubMed
16.
Huber SJ, Paulson GW, Shuttleworth EC: Relationship of motor symptoms, intellectual impairment, and depression in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1988, 51 (6): 855-858. 10.1136/jnnp.51.6.855.CrossRefPubMedPubMedCentral
17.
Yamamoto M: Depression in Parkinson's disease: its prevalence, diagnosis, and neurochemical background. J Neurol. 2001, 248 (Suppl 3): III5-III11.PubMed
18.
McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM: Reporting recommendations for tumor marker prognostic studies. J Clin Oncol. 2005, 23 (36): 9067-9072. 10.1200/JCO.2004.01.0454.CrossRefPubMed
19.
Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C, Giladi N, Holloway RG, Moore CG, Wenning GK, Yahr MD, Seidl L: Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord. 2004, 19 (9): 1020-1028. 10.1002/mds.20213.CrossRefPubMed
20.
Firbank MJ, Molloy S, McKeith IG, Burn DJ, O'Brien JT: Longitudinal change in 99mTcHMPAO cerebral perfusion SPECT in Parkinson's disease over one year. J Neurol Neurosurg Psychiatry. 2005, 76 (10): 1448-1451. 10.1136/jnnp.2004.058685.CrossRefPubMedPubMedCentral
21.
Huang C, Tang C, Feigin A, Lesser M, Ma Y, Pourfar M, Dhawan V, Eidelberg D: Changes in network activity with the progression of Parkinson's disease. Brain. 2007, 130 (7): 1834-1846. 10.1093/brain/awm086.CrossRefPubMedPubMedCentral
22.
Winogrodzka A, Bergmans P, Booij J, van Royen EA, Janssen AG, Wolters EC: [123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease. J Neural Transm. 2001, 108 (8–9): 1011-1019.CrossRefPubMed
23.
Parkinson Study Group: Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA. 2002, 287 (13): 1653-1661. 10.1001/jama.287.13.1653.CrossRef
24.
Hobart JC, Cano SJ, Zajicek JP, Thompson AJ: Rating scales as outcome measures for clinical trials in neurology: problems, solutions, and recommendations. Lancet Neurol. 2007, 6 (12): 1094-1105. 10.1016/S1474-4422(07)70290-9.CrossRefPubMed
25.
Taylor KS, Counsell CE, Harris CE, Gordon JC, Smith WC: Pilot study of the incidence and prognosis of degenerative Parkinsonian disorders in Aberdeen, United Kingdom: methods and preliminary results. Mov Disord. 2006, 21 (7): 976-982. 10.1002/mds.20866.CrossRefPubMed
26.
27.
Altman DG: Relation between two continuous variables. Practical Statistics for Medical Research. 1993, London: Chapman & Hall, 277-324.
28.
Brown H, Prescott R: Repeated measures data. Applied mixed models in medicine. 2006, Chichester: J. Wiley, 215-270. 2CrossRef
29.
30.
31.
Metadata
Title
A systematic review of biomarkers for disease progression in Parkinson’s disease
Authors
David JM McGhee
Pamela L Royle
Paul A Thompson
David E Wright
John P Zajicek
Carl E Counsell
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2013
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-13-35

Other articles of this Issue 1/2013

BMC Neurology 1/2013 Go to the issue

Research article

Higher numbers of circulating endothelial progenitor cells in stroke patients with intracranial arterial stenosis

Research article

5-year survival and rehospitalization due to stroke recurrence among patients with hemorrhagic or ischemic strokes in Singapore

Study protocol

Gothenburg very early supported discharge study (GOTVED) NCT01622205: a block randomized trial with superiority design of very early supported discharge for patients with stroke

Research article

Clinical significance of plasma VEGF value in ischemic stroke - research for biomarkers in ischemic stroke (REBIOS) study

Research article

Relationships among serum C-reactive protein, receptor for advanced glycation products, metabolic dysfunction, and cognitive impairments

Research article

Comparison of once-daily versus twice-daily combination of Ropinirole prolonged release in Parkinson’s disease