Table 2.
Brief overview of suggested Core OM in disease-modifying PD trials
| Category | Instrument/Test | Brief description | Rater | Delivery | Length (min) | Strengths | Limitations |
| Global – Generic | CGI-I | 7-point categorical scale (level of improvement/worsening) to determine the progress and treatment response of patients | Clinician | In-person or remote | <5 | BriefOverall assessmentBroad use in clinical trials | No clinimetric data outside PsychiatrySubjectiveNot PD-specific |
| Global – PD-related | MDS-UPDRS | PD-specific scale with 4 parts: I: non-motor experiences of daily living (IA and IB) II: motor experiences of daily living III: motor examinationIV: motor complications | IB, II: PatientIA, III, IV: Clinician | In-personDeliverable remotely except for part III (Rigidity and Postural stability items) | 30– 40 (whole) | Gold standard OM in most PD trialsComprehensive (motor, non-motor, medication-related complications) Widely used in trialsGood clinimetric propertiesClinically meaningful cut-offs availablePD-specific | LengthyRequires trainingAssociated costsNeeds in-person assessment (part III)Part I: screening of NMSPart III: excessive weight on tremor |
| LEDD* | Summary of total daily antiparkinsonian medications | Clinician | In-person or remote | <5 | PD-specific Widely used in PD (including disease-modifying trials) Potential indirect measure of efficacy | Different methods for calculation, although standard formulae suggested | |
| Motor | Hoehn &Yahr scale | 5-stage categorization of PD according to functional disability | Clinician | In-person | <5 | PD-specific Brief Excellent clinimetric properties Wide experience in PD clinical trials | Non-granular – less responsive to change than other OMs No minimal clinically important difference |
| Falls | Question about falls (such as the International ProFaNE falls definition)** | One question: In the past n months, have you had any fall including a slip or trip in which you lost your balance and landed on the floor or ground or lower level? | Clinician or patient | In-person or remote | <5 | Very brief Administrable remotely International definition | Less detailed than other falls scales Not PD-specific |
| Cognition | MoCA | 30-point test assessing different cognitive domains, namely: short-term memory, visuospatial abilities, executive functions, attention, concentration, working memory, language, and orientation to time and place | Clinician | In-person, but deliverable remotely | 10 (20 if remote) | Brief Used in PD (including disease-modifying trials) Sensitive to change, less ceiling effect than MMSE Excellent clinimetric properties Clinically meaningful cut-offs defined for PD-MCI and PDD | Requires training Limited sensitivity for specific cognitive domains Low variability of scores (limited sensitivity to change) Not PD-specific |
| Depression | PHQ-9 | Depression module from the PRIME-MD diagnostic instrument for common mental disorders, scores each of the 9 DSM-IV depression criteria from 0 to 3 according to frequency | Patient | In-person or remote | 3 | BriefUsed in PD (including disease-modifying trials) | Less sensitive to change than others (e.g., GDS-15)Not PD-specific |
| Disability | S&E ADL | Scale measuring the level of functional independence in 10 levels of ability to perform various chores, distributed in 10% intervals from 0% (“Bedridden”) to 100% (“Completely independent”) | Patient or clinician | In-person or remote | <5 | BriefWidely availableUsed in PD (including disease-modifying trials) Good clinimetric propertiesResponsive to change | Not PD-specific |
| Capability | ICECAP | Scale measuring wellbeing beyond HR-QoL for a more meaningful economic assessment of interventions ICECAP-A (adults) has 5 questions on: stability, attachment, achievement, autonomy, and enjoyment; ICECAP-O (older people) covers: attachment, security, role, enjoyment, and control. | Patient | In-person or remote | <5 | BriefEasy to completePreviously used in similar patient populationsFree to useIf collected at repeated timepoints then it allows calculation of CALYs | Not PD-specificCannot be used in standard cost-utility analysis as it does not return QALYs that are required for cost-utility analysis |
| HR-QoL – Generic | EQ-5D-5L | Measure of perceived health, constituted by 5 items with 5 response options and a VAS on the health status on the day of questionnaire completion, as perceived by the patient, from 0 to 100 | Patient or clinician | In-person or remote | <5 | BriefWidely used, including in PDGood clinimetric propertiesIf collected at repeated timepoints then it allows calculation of QALYs that can be used in cost-utility analysis, which is commonly used in health technology assessment | Not PD-specificNot as granular as other OMNo clinically meaningful cut-off available |
| Category | Instrument/Test | Brief description | Rater | Delivery | Length (min) | Strengths | Limitations |
| HR-QoL – PD-specific | PDQ-8 | Short version of the PDQ-39, contains 8 items representing each of the 8 different domains in the PDQ-39, each of them asking about the frequency a PD-related issue on daily life, with 5 possible answers for each of them | Patient | In-person or remote | 5 | BriefPD-specificGood clinimetric propertiesSensitive to change and responsive to interventionsMinimal important difference availableCan be mapped to utility scores from EQ-5D-3L, so if collected at repeated timepoints then allows approximate calculation of QALYs that can be used in cost-utility analysis, which is commonly used in health technology assessment | Requires a licenseLower reliability and validity than PDQ-39 |
| Resource use | Study-specific combination of CSRI and EHR | Resources used in the treatment and care pathways can be captured from participants/carers using the CSRI questionnaire, and/or from electronic health records, according to the specific study context | Patient, carer, site staff | In-person or remote | 5– 20 | CSRI can be tailored to meet specific study requirements and capture varied types of relevant resource informationEHR can reduce bias and missing data, and patient burden, and allow data collection outside the trial follow-up periodThe combination of CSRI and EHR to capture resource use allows advantages of each to be maximized and disadvantages minimized | Requires extensive input from trial team and other stakeholders during design of data collection plansCSRI can be burdensome for patients/carers to completeEHR can miss important information as they are not generally designed with research in mindEHR can be expensive to obtain |
*LEDD is recommended as Core in trials included PD patients taking symptomatic medication (i.e., not drug-naïve). **A question enquiring about falls is recommended as Core, and as an example, the ProFaNE falls definition is described under this section. CALYs, Capability-Adjusted Life-Years; CGI-I, Clinician Global Impression scale – Improvement; CSRI, Client Service Receipt Inventory; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; HER, Electronic Health Records; HR-QoL, Health-Related Quality of Life; ICECAP, ICEpop CAPability measures; LEDD, Levodopa-Equivalent Daily Dose; MDS-UPDRS, Movement Disorders Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; NMS, non-motor symptoms; OM, outcome measure; PD: Parkinson’s disease; PDD, Parkinson’s disease dementia; PD-MCI, Parkinson’s Disease with mild cognitive impairment; PDQ-39, 39-item Parkinson’s Disease Questionnaire; PDQ-8, 8-item Parkinson’s Disease Questionnaire; PHQ-9, 9-item Patient Health Questionnaire; PPIE, Patient and Public Involvement and Engagement; PRIME-MD, PRIMary care Evaluation of Mental Disorders; QALYs, Quality-Adjusted Life-Years; S&E ADL, Schwab and England Activities of Daily Living Scale; VAS, Visual Analogue Scale.