Psychometric Properties of Clinical Indicators for Identification and Management of Advanced Parkinson's Disease: Real-World Evidence From G7 Countries

Abstract

Introduction: Standardized and validated criteria to define advanced Parkinson's disease (PD) or identify patient eligibility for device-aided therapy are needed. This study assessed the psychometric properties of clinical indicators of advanced PD and eligibility for device-aided therapy in a large population.

Methods: This retrospective analysis of the Adelphi Parkinson's Disease Specific Programme collected data from device-aided therapy-naïve people with PD in G7 countries. We assessed the presence of 15 clinical indicators of advancing PD and seven indicators of eligibility for device-aided therapy in patients classified with advanced PD or as eligible for device-aided therapy by the treating physician. Accuracy was assessed using area under the curve (AUC) and multivariable logistic regression models. Construct validity was examined via known-group comparisons of disease severity and burden among patients with and without each clinical indicator.

Results: Of 4714 PD patients, 14.9% were classified with advanced PD and 17.5% as eligible for device-aided therapy by physician judgment. The presence of each clinical indicator was 1.9- to 7.3-fold more likely in patients classified with advanced PD. Similarly, the presence of device-aided therapy eligibility indicators was 1.8- to 5.5-fold more likely in patients considered eligible for device-aided therapy. All indicators demonstrated high clinical screening accuracy for identifying advanced PD (AUC range 0.84-0.89) and patients eligible for device-aided therapy (AUC range 0.73-0.80). The Unified Parkinson's Disease Rating Scale (UPDRS) score, cognitive function, quality of life, and caregiver burden were significantly worse in indicator-positive patients.

Conclusion: Specific clinical indicators of advanced PD and eligibility for device-aided therapy demonstrated excellent psychometric properties in a large sample, and thus may provide an objective and reliable approach for patient identification and treatment optimization.

Keywords: Accuracy; Advanced Parkinson’s disease; Clinical indicators; Device-aided therapy eligibility; Validity.

Fig. 1

Multivariable logistic regression models evaluating the relationship between the 15 clinical indicators and physician assessment of advanced Parkinson’s disease (PD) (a) and the seven device-aided therapy criteria and provider assessment of device-aided therapy eligibility (b). Odds ratio (OR) was adjusted to account for differences by country, age, gender, PD stage, years since PD diagnosis, and number of comorbidities. CI Confidence interval

Fig. 2

Diagnostic accuracy of the 15 Delphi clinical indicators of suspected advanced PD. The area under the curve (AUC; blue line) was calculated from the sensitivity (i.e., presence of the indicator in patients with advanced PD according to physician’s judgment) and specificity (i.e., absence of the indicator in patients with early/intermediate PD according to physician’s judgment). Correct classification rate (pink line) was the percentage of patients with a given indicator who were classified as having advanced PD by the physician (expressed above as percentage/100). An AUC ≥ 0.7 and correct classification rate ≥ 70% were considered appropriate for screening performance. AUC model was adjusted to account for differences by country, age, gender, PD stage, years since PD diagnosis, and number of comorbidities. NMS Non-motor symptom

Fig. 3

Clinical accuracy of the seven device-aided therapy indicators for identifying patients eligible for device-aided therapy. The area under the curve (AUC; blue line) was calculated from the sensitivity (i.e., presence of the indicator in patients eligible for device-aided therapy according to physician’s judgment) and specificity (i.e., absence of the indicator in patients ineligible for device-aided therapy according to physician’s judgment). Correct classification rate (pink line) was the percentage of patients with a given indicator who were classified as being eligible for device-aided therapy by the physician (expressed above as percentage/100). An AUC ≥ 0.7 and correct classification rate ≥ 70% were considered appropriate for screening performance. AUC model adjusted to account for differences by country, age, gender, PD stage, years since PD diagnosis, and number of comorbidities

Fig. 4

Construct validity of the 15 Delphi clinical indicators of advanced PD based on: a UPDRS total score, b MMSE score, c PDQ-39 Summary Index score, d ZBI score. All differences between presence and absence of a clinical indicator were statistically significantly different (p < 0.01, t test)—except where marked with an asterisk. Numbers under each graph represent the following indicators: 1 Moderate/severe troublesome motor fluctuations, 2 ≥ 2 h ‘off’-time/waking day, 3 ≥ 1 h troublesome dyskinesia/waking day, 4 at least moderate level of dyskinesia, 5 troublesome dysphagia, 6 at least 5 times oral levodopa/day, 7 has at least mild dementia, 8 non-transitory troublesome hallucinations, 9 moderate/severe psychosis, 10 moderate/severe non-motor symptom fluctuations, 11 moderate/severe sleep disturbances, 12 falls most/all the time, 13 moderate/severe limitations with activities of daily living, 14 not able to perform complex tasks at least some of the time, 15 at least moderate impaired mobility. MMSE Mini-Mental State Examination, PDQ-39 39-item Parkinson’s Disease Questionnaire, UPDRS Unified Parkinson’s Disease Rating Scale, ZBI Zarit Burden Interview

Fig. 5

Construct validity of the seven device-aided therapy criteria based on: a UPDRS total score, b MMSE score, c PDQ-39 Summary Index score, d ZBI score. All differences between presence and absence of device-aided therapy criteria were statistically significantly different (p < 0.01, t test). Numbers under each graph represent the following indicators: 1 Troublesome dyskinesia, 2 ≥ 2 h ‘off’-time/waking day, 3 ‘Off’-period postural instability, 4 dystonia with pain, 5 freezing of gait during ‘off’, 6 night-time sleep disturbances, 7 limited activities of daily living