Table 1.
Selected outcome measures for consideration and level of recommendation
| Category | Instrument/Test | NINDS-CDE v2.0 classification | Proposed classification for disease-modifying trials |
| Global – Generic | CGI-I | Supplemental-HR | Core |
| Global – PD-specific | MDS-UPDRS (and UPDRS, and remote versions) | Core | Core |
| LEDD | NI | Core* | |
| Motor – General | MDS-UPDRS Gait-axial score | NI | Supplemental |
| Hoehn &Yahr scale | Core | Core | |
| UDysRS | Supplemental-HR | Supplemental | |
| Gait, balance, and falls | Question about falls (e.g., ProFaNE falls definition) | NI | Core |
| Mini-BESTest | NI | Supplemental | |
| Berg Balance Scale | NI | Supplemental | |
| FES-I | NI | Supplemental | |
| ABC Scale | NI | Supplemental | |
| Speech and swallowing | SWAL-QOL | Supplemental | Supplemental |
| SDQ | Supplemental | Supplemental | |
| ROMP | Supplemental | Supplemental | |
| Fluctuations | PD Home Diary (Hauser Diary) | Supplemental-HR | Supplemental |
| CAPSIT-PD On/Off Diary | Supplemental-HR | Supplemental | |
| WOQ-9 and WOQ-19 | Supplemental-HR | Supplemental | |
| Non-motor – General | NMSQ | Supplemental | Supplemental |
| NMSS | NI | Supplemental | |
| MDS-NMS | Supplemental-HR | Supplemental | |
| Fatigue | FSS | Supplemental | Supplemental |
| Pain | KPPS | Supplemental | Supplemental |
| Sleep | PDSS-2 | Supplemental-HR | Supplemental |
| ESS | Supplemental-HR | Supplemental | |
| Depression | PHQ-9 | Supplemental | Core |
| GDS-15 | Supplemental-HR | Supplemental | |
| C-SSRS | Supplemental-HR | Supplemental** | |
| Apathy | AS | Supplemental-HR | Supplemental |
| AES | NI | Supplemental | |
| LARS | Supplemental-HR | Supplemental | |
| Psychosis | SAPS-PD | Supplemental-HR | Supplemental |
| eSAPS-PD | Supplemental-HR | Supplemental | |
| Autonomic dysfunction | SCOPA-AUT | Supplemental | Supplemental |
| Cognitive measures | MoCA | Core | Core |
| DRS-2 | Supplemental (MDRS) | Supplemental | |
| PD-CRS | Supplemental | Supplemental | |
| ACE-III | Supplemental | Supplemental | |
| ADAS-Cog | Supplemental | Supplemental | |
| MMSE | Supplemental | Supplemental | |
| MMP | NI | Supplemental | |
| SCOPA-COG | Supplemental | Supplemental | |
| Disability | S&E ADL | Supplemental-HR | Core |
| FSQ | NI | Supplemental | |
| Capability | ICECAP | NI | Core |
| Carer measures | PQoL Carers | NI | Supplemental |
| PDQ-Carer | NI | Supplemental | |
| Zarit Burden Interview | NI | Supplemental | |
| HR-QoL – Generic | EQ-5D-5L | Supplemental-HR (EQ-5D) | Core |
| SF-36 | Supplemental-HR | Supplemental | |
| SF-12 | NI | Supplemental | |
| PROMIS/Neuro-QoL | Supplemental-HR (Neuro-QoL) | Supplemental | |
| HUI | NI | Supplemental | |
| HR-QoL – PD-specific | PDQ-8 | NI | Core |
| PDQ-39 | Supplemental-HR | Supplemental | |
| Resource use | CSRI in combination with EHR | NI | Core |
| EHR in combination with CSRI | NI | Core | |
| Milestone-based OM | To be determined (see Supplement) | NI | Exploratory |
| Digital measures – Active only | OPDC Smartphone app | Exploratory | Exploratory |
| CloudUPDRS smartphone-based measures of limb-specific tremor/bradykinesia | Exploratory | Exploratory | |
| Mobility lab system (APDM)-measures acquired typically in controlled settings | Exploratory | Exploratory | |
| mPower smartphone-derived composite (dominantly motor) impairment score | Exploratory | Exploratory | |
| Digital measures – Passive only | PKG-based proxy measures of whole-body tremor/bradykinesia/dyskinesia | Exploratory | Exploratory |
| MM4D-based proxy measure of whole-body tremor/dyskinesia | Exploratory | Exploratory | |
| Axivity (AX3 &AX6) gait accelerometer | Exploratory | Exploratory | |
| Digital measures – Active and passive | Roche smartphone app | Exploratory | Exploratory |
| Other digital/timed motor measures | Exploratory | Exploratory | |
| Quantitative motor measures | TUG 3 meter | NI | Supplemental |
| Purdue Pegboard test | NI | Supplemental | |
| Alternate tap test | NI | Supplemental | |
| BRAIN tap test | NI | Supplemental | |
| 9-hole peg test | NI | Supplemental | |
| Composite quantitative motor measures | OPDC composite clinical score | NI | Exploratory |
| Molecular neuroimaging | Dopaminergic SPECT | NI (PET-SPECT Localization: Supplemental – HR; Supplemental) | Exploratory |
| Dopaminergic PET | See above | Exploratory | |
| Non-dopaminergic SPECT | See above | Exploratory | |
| Non-dopaminergic PET | See above | Exploratory | |
| Magnetic Resonance Spectroscopy | Supplemental-HR | Exploratory | |
| Structural neuroimaging | T1 Structural sequence | Supplemental-HR | Exploratory |
| Diffusion imaging | NI | Exploratory | |
| Multiple Parametric Mapping Protocol | NI | Exploratory | |
| Neuromelanin | NI | Exploratory | |
| Iron-sensitive sequences | NI | Exploratory | |
| Wet biomarkers | Plasma/serum NfL | NI | Exploratory |
| Plasma tau | NI | Exploratory | |
| Plasma α-syn | NI | Exploratory | |
| CSF NfL | NI | Exploratory | |
| CSF tau | NI | Exploratory | |
| CSF α-syn | NI | Exploratory | |
| CSF α-syn aggregation | NI | Exploratory | |
| CSF Aβ | NI | Exploratory | |
| Salivary markers (e.g., salivary α-syn) | NI | Exploratory |
*Change in LEDD is recommended as Core in trials including PD patients taking symptomatic medication (i.e., not drug-naïve). **Administration of the C-SSRS is recommended if screening question on the PHQ-9 is >0. Core, to be included in all disease-modifying PD trials; Supplemental, recommended but not required for all disease-modification studies in PD depending on the particular trial; Exploratory, may fill current gaps once validation is complete but require further validation; ABC Scale, Activities-Specific Balance Confidence Scale; ACE-III, Addenbrooke’s Cognitive Examination; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive Subscale; AES, Apathy Evaluation Scale; AS, Apathy Scale; BRAIN, Bradykinesia-Akinesia Incoordination; C-SSRS, Columbia Suicide Severity Rating Scale; CAPSIT-PD, Core assessment program for surgical interventional therapies in Parkinson’s disease; CGI-I, Clinical Global Impression Scale-Improvement; CSF, Cerebrospinal fluid; CSRI, Client Service Receipt Inventory; DRS-2, Mattis Dementia Rating Scale Second Edition; EHR, Electronic health records; EHR, Electronic Health Records; EQ-5D-5L, EuroQoL 5-dimension 5-level questionnaire; eSAPS-PD, Scale for the Assessment of Positive Symptoms in Parkinson’s Disease, enhanced version; ESS, Epworth Sleepiness Scale; FES-I, Falls Efficacy Scale International; FSQ, Functional Status Questionnaire; FSS, Fatigue Severity Scale; GDS-15, 15-item Geriatric Depression Scale; HUI, Health Utility Index; ICECAP, ICEpop CAPability measures; KPPS, King’s Parkinson’s Disease Pain Scale; LARS, Lille Apathy Rating Scale; LEDD, Levodopa-Equivalent Daily Dose; MDRS, Mattis Dementia Rating Scale; MDS-NMS, Movement Disorder Society-sponsored Non-motor Rating Scale; MDS-UPDRS, Movement Disorders Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale; Mini-BESTest, Mini-Balance Evaluation Systems Test; MM4D, Motor fluctuations Monitor for Parkinson’s Disease; MMP, Mini-Mental Parkinson; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; NfL, neurofilament light chain; NI, not included; NINDS-CDE v2.0, National Institute of Neurological Disorders and Stroke Common Data Elements version 2.0; NMSQ, Non-motor Symptoms Questionnaire; NMSS, Non-motor Symptoms Scale; OPDC, Oxford Parkinson’s Disease Centre; PD-CRS, Parkinson’s Disease-Cognitive Rating Scale; PDQ-8, 8-item version of the Parkinson’s Disease Questionnaire; PDQ-39, 39-tem version of the Parkinson’s Disease Questionnaire; PDQ-Carer, 29-item Parkinson Disease Questionnaire for Carers; PDSS-2, Parkinson’s Disease Sleep Scale-2; PET, positron emission tomography; PHQ-9, 9-item Patient Health Questionnaire; PKG, Parkinson’s Personal KinetiGraph® (formerly Parkinson’s KinetiGraph®); PQoL carers, carers quality-of-life questionnaire for parkinsonism; ProFaNE, Prevention of Falls Network Earth; PROMIS/Neuro-QoL, Patient-Reported Outcomes Measurement Information System/Quality of Life in Neurological Disorders; ROMP, Radboud Oral Motor Inventory for Parkinson’s Disease; S&E ADL SCALE, Schwab and England Activities of Daily Living Scale; SAPS-PD, Scale for the Assessment of Positive Symptoms in Parkinson’s Disease; SCOPA-AUT, Scales for Outcomes in Parkinson’s disease-AUTonomic symptoms; SCOPA-COG, Scales for Outcomes in Parkinson’s disease- COGnitive symptoms; SDQ, Swallowing Disturbance Questionnaire; SF-12, 12-Item Short Form Survey; SF-36, 36-Item Short Form Survey; SPECT, single-photon emission computerized tomography; Supplemental-HR, Supplemental-Highly Recommended; SWAL-QOL, Generic Scale for Dysphagia-Related Outcomes (Quality of Life); TUG, Timed Up and Go; UPDRS, Unified Parkinson’s Disease Rating Scale; UDysRS, Unified Dyskinesia Rating Scale; WOQ-9, 9-item Wearing Off Questionnaire; WOQ-19, 19-item Wearing Off Questionnaire; α-syn, alpha-synuclein; Aβ, amyloid beta