title: How valid is dopamine transporter imaging as a surrogate marker in research trials in Parkinson's disease?
abstract: To use functional imaging data as indices of disease progression, it is essential that methods are valid. It is not possible for that validation to come from pathology and the methods can only gain validity from the relationship to clinical indices of progression. Validity as a measurement of disease progression depends upon sensitivity to clinical progression, low scan-to-scan error, and resilience to confounding effects. Data from the available dopamine transporter (DAT) positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies are examined for these three key factors. Presently, there are insufficient data to enable the satisfactory design of neuroprotection studies and to enable statements on their relevance to disease progression and neuroprotection. The recently completed CALM-PD neuroimaging study is examined. There is sufficient doubt surrounding the sensitivity, reproducibility, and confounding effects in this study that these data should not be used to formulate a decision on de novo therapy in Parkinson's disease.
authors.affiliation: Hurstwood Park Neurological Centre, Princess Royal Hospital, East Sussex, United Kingdom. paul.morrish@bsuh.nhs.uk
authors.forename: Paul K
authors.initials: PK
authors.lastname: Morrish
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000000981:diagnostic imaging*; D002986:Clinical Trials as Topic; D018450:Disease Progression; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents