Rotigotine transdermal patch in Chinese patients with early Parkinson's disease: A randomized,double-blind,placebo-controlled pivotal study

IntroductionTwo phase3 studies (SP512; SP513) involving mostly Caucasian patients showed that rotigotine (≤8 mg/24 h) was efficacious and welltolerated in early-stage Parkinson's disease (PD). We report results from a phase 3 study (SP0914/NCT01646268) investigating rotigotine in Chinese patients with early-stage PD.MethodsPatients were randomized 1:1 to rotigotine or placebo, titrated over 1–4 weeks, maintained at optimal/maximum dose (≤8 mg/24 h) for 24 weeks. Primary efficacy variable: change in Unified Parkinson's Disease Rating Scale (UPDRS) II + III total score from Baseline to End-of-Maintenance. Secondary variables: UPDRS II + III responders (≥20% decrease in UPDRS II + III) and changes in UPDRS II (activities of daily living [ADL]) and III (motor examination) subscores.ResultsOf 247 patients randomized, 113/124 (91.1%) rotigotine- and 107/123 (87.0%) placebo-treated patients completed the study. Patients: mean (SD) age: 59.4 (10.2) years; time since PD diagnosis: 1.01 (1.22) years, 60.7% male. Rotigotine significantly improved UPDRS II + III total score (change from Baseline LSmean [95%CI] treatment difference, −4.82 [−7.18 to −2.45]; P < 0.0001). UPDRS II + III responder rates were higher with rotigotine (42.3% vs 22.3%; P = 0.0006). UPDRS II and III subscores improved with rotigotine (both subscores: P < 0.0005 vs. placebo). Most frequent adverse events (AEs): nausea (8.9% rotigotine, 3.3% placebo), dizziness (8.1%, 5.7%), pruritus (8.1%, 4.1%), somnolence (8.1%, 3.3%), erythema (6.5%, 1.6%), and vomiting (5.6%, 1.6%). Thirteen (5.3%) patients discontinued due to AEs (6 rotigotine, 7 placebo).ConclusionsRotigotine was efficacious in Chinese patients with early-stage PD, providing benefits to control of ADL and motor function. Rotigotine was generally welltolerated, with similar AEs to those observed in Caucasian patients.     

Rotigotine and specific non-motor symptoms of Parkinson's disease: Post hoc analysis of RECOVER

BackgroundNon-motor symptoms of Parkinson's disease (PD) represent major causes of morbidity. RECOVER, a randomized controlled trial of rotigotine transdermal system, was the first prospective controlled trial to use the Non-Motor Symptoms Scale (NMSS) as an exploratory outcome for assessment of treatment effects on non-motor symptoms in PD. Rotigotine improved NMSS total score compared with placebo, and the “Sleep/fatigue” and “Mood/apathy” domains. This post hoc analysis further characterizes the effects of rotigotine on sleep/fatigue and mood/apathy.MethodsPatients with PD and unsatisfactory early-morning motor impairment were randomized to transdermal patches of rotigotine (2–16 mg/24 h) or placebo. Treatment was titrated to optimal dose over 1–8 weeks, maintained for 4 weeks. The NMSS was assessed at baseline and end of treatment. Post hoc analyses are presented for individual items of the “Sleep/fatigue” and “Mood/apathy” domains. The interpretation of p-values is considered exploratory in nature.ResultsOf 287 patients randomized, NMSS data were available for 267 patients (178 rotigotine, 89 placebo). Within the “Sleep/fatigue” domain there was a significant difference, in favor of rotigotine, in change from baseline score in 1 of 5 items: “fatigue (tiredness) or lack of energy” (ANCOVA, p < 0.0001). Within the “Mood/apathy” domain, there were significant differences in favor of rotigotine in 4 of 7 items: “lost interest in surroundings” (p < 0.0001), “lost interest in doing things” (p < 0.0001), “seems sad or depressed” (p < 0.01), and “difficulty experiencing pleasure” (p < 0.05).ConclusionsRotigotine transdermal system may improve non-motor symptoms such as fatigue, symptoms of depression, anhedonia, and apathy in patients with PD; further prospective controlled studies are required to confirm this post hoc analysis.     

How well do Parkinson's disease patients turn in bed? Quantitative analysis of nocturnal hypokinesia using multisite wearable inertial sensors

BackgroundNocturnal hypokinesia/akinesia is a distressing symptom in patients with Parkinson's disease (PD). However, it is difficult to accurately monitor these symptoms based on clinical interviews alone.ObjectivesTo quantitatively compare nocturnal movements of PD patients with their spouses by using multisite inertial sensors and to correlate these parameters with disease severity scores.MethodsNocturnal movements in 19 PD couples (mild-moderate stage) were assessed and compared using wearable sensors (limbs and trunk) for one night at their homes. Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, number of getting out of bed, and limb movements. Each activity was compared to sleep diary, and video recording for accuracy.ResultsPD patients significantly had fewer rolling over (p = 0.048), turned with smaller degree (p = 0.007), less velocity (p = 0.011), and acceleration (p < 0.001), but had more episodes of getting out of bed (p = 0.03, nocturia) when compared to their spouses. Moderate and significant correlations were observed between the mean duration of rolling over and the Unified Parkinson's Disease Rating Scale-Axial score, and Nocturnal Akinesia Dystonia and Cramp Score. The number of leg movements (predominant side) significantly correlated with REM behavior disorder single-question screen. Episodes of nocturia correlated with total and bedtime levodopa equivalent dose. Several other correlations were also observed.ConclusionOur study was able to demonstrate quantitatively the presence of nocturnal hypokinesia in PD patients. This problem correlated with daytime axial motor and nonmotor symptoms. Treatment strategy for PD should be based on a comprehensive review of both day- and nighttime symptoms.     

Rotigotine vs ropinirole in advanced stage Parkinson's disease: A double-blind study

ObjectiveTo confirm the superiority of transdermal rotigotine up to 16 mg/24 h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy.MethodsThis trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15 mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period.ResultsThe difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was −6.4 ± 1.2 (95% CI: −8.7 to −4.1; p < 0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was −1.4 ± 1.0 (95% CI: −3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P < 0.001). No other safety issue was noted.ConclusionsRotigotine was well tolerated at doses up to 16 mg/24 h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group.     

Quantitative mobility measures complement the MDS-UPDRS for characterization of Parkinson's disease heterogeneity

IntroductionEmerging technologies show promise for enhanced characterization of Parkinson's Disease (PD) motor manifestations. We evaluated quantitative mobility measures from a wearable device compared to the conventional motor assessment, the Movement Disorders Society-Unified PD Rating Scale part III (motor MDS-UPDRS).MethodsWe evaluated 176 PD subjects (mean age 65, 65% male, 66% H&Y stage 2) during routine clinic visits using the motor MDS-UPDRS and a 10-min motor protocol with a body-fixed sensor (DynaPort MT, McRoberts BV), including the 32-ft walk, Timed Up and Go (TUG), and standing posture with eyes closed. Regression models examined 12 quantitative mobility measures for associations with (i) motor MDS-UPDRS, (ii) motor subtype (tremor dominant vs. postural instability/gait difficulty), (iii) Montreal Cognitive Assessment (MoCA), and (iv) physical functioning disability (PROMIS-29). All analyses included age, gender, and disease duration as covariates. Models iii-iv were secondarily adjusted for motor MDS-UPDRS.ResultsQuantitative mobility measures from gait, TUG transitions, turning, and posture were significantly associated with motor MDS-UPDRS (7 of 12 measures, p < 0.05) and motor subtype (6 of 12 measures, p < 0.05). Compared with motor MDS-UPDRS, several quantitative mobility measures accounted for a 1.5- or 1.9-fold increased variance in either cognition or physical functioning disability, respectively. Among minimally-impaired subjects in the bottom quartile of motor MDS-UPDRS, including subjects with normal gait exam, the measures captured substantial residual motor heterogeneity.ConclusionClinic-based quantitative mobility assessments using a wearable sensor captured features of motor performance beyond those obtained with the motor MDS-UPDRS and may offer enhanced characterization of disease heterogeneity.     

Tailoring the use of wearable systems and telehealth for Parkinson's disease

The increasing need for remote and distributed methods to provide medical care for People with Parkinson Disease has increased the importance of additional tools to monitor symptoms of interest. We present data from a randomized trial of followup care delivered via traditional face to face visits with symptom diaries versus telehealth followup with wearable sensors.     

Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.

The objective of this study is to conduct a dose-finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5-HT(1A) agonist properties and additional high affinity for D(3) and D(4) receptors. An open label study documented improvements in PD patients with levodopa-induced dyskinesia. There is no precedent for study designs or outcome measures in pivotal trials of antidyskinesia therapies. The approach used here was a multicenter, randomized, placebo-controlled, double-blind, parallel study. Included were PD patients optimized to levodopa and dopaminergic drugs with moderately disabling dyskinesias present greater than or equal to 25% of the waking day. Interventions included sarizotan 2, 4, or 10 mg/day or matching placebo, given in two doses. There were two outcome measures: the primary measure was change from baseline in diary-based on time without dyskinesia; the secondary measures were change from baseline in scores on the Abnormal Involuntary Movement Scale (AIMS), the composite score of Unified Parkinson's Disease Rating Scale (UPDRS) Items 32+33 (dyskinesia duration and disability) and total UPDRS. A total of 398 subjects were randomized, with 381 included in the intention-to-treat population. No significant changes occurred on sarizotan compared to placebo on any diary-based measure of dyskinesia or the AIMS score. The composite score of UPDRS Items 32+33 was significantly improved with 2 mg/day sarizotan, with a trend at 10 mg/day. Adverse events were not significantly different in sarizotan- and placebo-treated patients, but off time significantly increased with sarizotan 10 mg/day. Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia. To test its role in abating dyskinesia, future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome.     

Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole.

Rotigotine is a new, non-ergot dopamine agonist formulated in a transdermal delivery system. The present study was to investigate the efficacy and safety of the rotigotine transdermal patch in the treatment of early Parkinson's disease. Patients (n = 561) were randomized to rotigotine, ropinirole, or placebo. The titration period was up to 13 weeks, and there was a minimum dose-maintenance period of 24 weeks for ropinirole and 33 weeks for rotigotine. The primary endpoint was the proportion of patients with a minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores. The responder rate in the rotigotine group was significantly higher than in the placebo group (52% vs. 30%, P < 0.0001). Transdermal rotigotine at doses < or =8 mg/24 h did not show noninferiority to ropinirole at doses < or =24 mg/day. In a post-hoc subgroup analysis, rotigotine < or =8 mg/24 hours had a similar efficacy to ropinirole at doses < or =12 mg/day. The rotigotine transdermal patch was well tolerated. The most common adverse events were application-site reactions, nausea, and somnolence. Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease.     

Botulinum toxin type A for drooling in Parkinson's disease: a double-blind, randomized, placebo-controlled study.

To investigate the safety and efficacy of botulinum toxin type A (BoNTX) treatment to reduce sialorrhea in Parkinson's disease (PD), a double-blind, randomized, placebo-controlled study enrolled 32 PD patients complaining of excessive drooling. Patients received either 50 U Botox in each parotid gland or placebo without using ultrasound guidance. Subjects treated with BoNTX experienced a reduction in both drooling frequency and familial and social disability (TimexGroup effect: P<0.01), as well as in saliva production (Time x Group effect: P<0.0001). No adverse events were recorded. BoNTX injections are safe and effective treatment for the management of PD-related drooling.     

Symptomatic efficacy of rasagiline monotherapy in early Parkinson's disease: Post-hoc analyses from the ADAGIO trial

BackgroundThe ADAGIO study included a large cohort of patients with early PD (baseline total-UPDRS = 20) who were initially randomized to rasagiline and placebo, thereby allowing analyses of symptomatic efficacy.MethodsPost-hoc analyses comparing the efficacy of rasagiline 1 mg/day (n = 288) versus placebo (n = 588) on key symptoms at 36 weeks, and on total-UPDRS scores over 72 weeks (completer population: rasagiline 1 mg/day n = 221, placebo n = 392) were performed.ResultsTreatment with rasagiline resulted in significantly better tremor, bradykinesia, rigidity and postural-instability-gait-difficulty scores at week 36 versus placebo. Whereas the placebo group experienced progressive deterioration from baseline (2.6 UPDRS points at week 36), patients in the rasagiline group were maintained at baseline values at week 60 (UPDRS-change of 0.3 points). At week 72, patients who had received continuous monotherapy with rasagiline experienced a worsening of only 1.6 points.ConclusionsTreatment with rasagiline maintained motor function to baseline values for at least a year with significant benefits observed in all key PD motor symptoms.     

Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease.

We completed a single site, double-blind, placebo-controlled, parallel design study of quetiapine for hallucinations in PD. Thirty-one subjects with PD and prominent visual hallucinations and Mini-Mental State Examination score >21 were randomly assigned in a 2:1 drug to placebo ratio, up to 200 mg daily of quetiapine or matching placebo given in two doses. They were seen at 3 weeks (100 mg/day) and 12 weeks (200 mg/day, with optional dose reduction). Evaluation included the Unified Parkinson's Disease Rating Scale (UPDRS), the Baylor PD Hallucination Questionnaire, and a battery of neuropsychological tests. The demographics between subjects randomized to drug (n = 21) vs. placebo (n = 10) were similar. The final dose of active drug was 200 (n = 11), 150 (n = 2), 100 (n = 3), and 75 (n = 1) mg per day. All placebo subjects were on the equivalent of 200 mg per day. The UPDRS Activities of Daily Living and Motor scores did not significantly change compared to placebo. Compared to placebo, there were no significant changes in our hallucination questionnaire, the Brief Psychiatric Rating Scale (BPRS), or question 12 (hallucination item) of the BPRS. There were no significant changes on any of the neuropsychological measures. Adverse events on drug included sedation (n = 9), but no drug-related adverse events precipitated discontinuation and none were rated as serious. Quetiapine, up to 200 mg daily, was well tolerated and did not worsen UPDRS scores; however, there was no significant improvement in psychosis rating scales compared to placebo. Larger doses of drug and greater sample sizes might be considered in future studies.     

Increasing access to specialty care: A pilot,randomized controlled trial of telemedicine for Parkinson's disease

We conducted a randomized, controlled pilot trial to evaluate the feasibility of providing subspecialty care via telemedicine for patients with Parkinson's disease residing in a remote community located ～130 miles from an academic movement disorders clinic. Study participants were randomized to receive telemedicine care with a movement disorder specialist at the University of Rochester or to receive their usual care. Participants in the telemedicine group received three telemedicine visits over six months. Feasibility, as measured by the completion of telemedicine visits, was the primary outcome measure. Secondary measures were quality of life, patient satisfaction, and clinical outcomes. Ten participants residing in the community were randomized to receive telemedicine care (n = 6) or their usual care (n = 4). Four nursing home patients were assigned to telemedicine. Those receiving telemedicine completed 97% (29 of 30) of their telemedicine visits as scheduled. At the study's conclusion, 13 of 14 study participants opted to receive specialty care via telemedicine. Compared with usual care, those randomized to telemedicine had significant improvements in quality of life (3.4 point improvement vs. 10.3 point worsening on the Parkinson's Disease Questionnaire 39; P = 0.04) and motor performance (0.3 point improvement vs. 6.5 point worsening on the Unified Parkinson's Disease Rating Scale, motor subscale; P = 0.03). Relative to baseline, nursing home patients experienced trends toward improvement in quality of life and patient satisfaction. Providing subspecialty care via telemedicine for individuals with Parkinson's disease living remotely is feasible. © 2010 Movement Disorder Society     

Comparing subjective and objective response to medications in Parkinson's disease patients using the Personal KinetiGraph™

BackgroundManagement of motor symptoms in Parkinson's Disease(PD) relies on subjective information provided by patients, the quality of which can be affected by many factors.RationaleObjective data collected during daily life could complement this information and improve management of motor symptoms.ObjectivesTo assess the usefulness of the Personal KinetiGraph (PKG) in characterizing the intensity and timing of motor symptoms in PD patients.MethodsRetrospective study of all PD patients followed at a tertiary academic movement disorders center assessed by PKG between December 1, 2016 and October 30, 2018. PKG was worn for 7 days prior to the clinical visit. We compared the information obtained from the interview and the clinical visit, and assessed the impact of the PKG on treatment decision making.Results170 PKG results were reviewed. PKG complemented patient input in 82.9%(141/170) and led to medication changes in 71%(100/141) of the complemented inputs. PKG contributed the least to correcting or complementing patients’ input when patients self-reported as undertreated (22%) and the most when patient were unable to answer all questions regarding motor response to individual doses (100%) (Fisher, p < 0.0001). The majority of patient undergoing 3 or 4 PKG encounters did not reach a controlled state as defined by PKG until the 3rd or 4th encounter, suggesting that repeated use of the PKG might be needed to help optimize motor control as therapy changes done after one encounter might not be enough.ConclusionsPKG might be useful in supplementing patient-provided information for accurate assessment and treatment plan.     

Effects of cognitive training in Parkinson's disease: A randomized controlled trial

BackgroundIn Parkinson's Disease (PD), cognitive dysfunctions which can reduce patients' quality of life occur frequently. Data on non-pharmacological intervention effects on cognitive functions in patients with PD are rare. The aim of this study was to examine the effects of different cognitive group trainings (structured vs. unstructured) on cognition, depression, and quality of life in non-demented PD patients.MethodsIn this randomized controlled trial, 65 non-demented patients with PD according to UK Brain Bank criteria (Hoehn & Yahr I-III) were allocated to one of two cognitive multi-component treatments (“NEUROvitalis”, a structured training, or the unstructured training “Mentally fit” with randomly assembled cognitive tasks, each including 12 group-sessions à 90 min over 6 weeks) or a waiting list control group (CG). A neuropsychological test battery was performed before and after the training.ResultsCompared to the CG, patients from the “NEUROvitalis” group improved in short-term memory (word list learning “Memo”: p < .01) and working memory (digit span reverse from “DemTect”: p < .05), whereas depression scores where reduced in the “Mentally fit” group (Beck Depression Inventory-II: p < .05). The “NEUROvitalis” group improved significantly more in working memory than the “Mentally fit” group (DemTect: p < .05).DiscussionCognitive and affective functions can be improved by cognitive trainings in PD patients. Specific effects (e.g. on memory and working memory versus depression) seem to be dependent on the type of training. Further research is needed to define long-term effects and the efficacy in PD patients with different extent of cognitive and neuropsychiatric symptoms.     

Feasibility and effects of home-based smartphone-delivered automated feedback training for gait in people with Parkinson's disease: A pilot randomized controlled trial

BackgroundInertial measurement units combined with a smartphone application (CuPiD-system) were developed to provide people with Parkinson's disease (PD) real-time feedback on gait performance. This study investigated the CuPiD-system's feasibility and effectiveness compared with conventional gait training when applied in the home environment.MethodsForty persons with PD undertook gait training for 30 min, three times per week for six weeks. Participants were randomly assigned to i) CuPiD, in which a smartphone application offered positive and corrective feedback on gait, or ii) an active control, in which personalized gait advice was provided. Gait, balance, endurance and quality of life were assessed before and after training and at four weeks follow-up using standardized tests.ResultsBoth groups improved significantly on the primary outcomes (single and dual task gait speed) at post-test and follow-up. The CuPiD group improved significantly more on balance (MiniBESTest) at post-test (from 24.8 to 26.1, SD∼5) and maintained quality of life (SF-36 physical health) at follow-up whereas the control group deteriorated (from 50.4 to 48.3, SD∼16). No other statistically significant differences were found between the two groups. The CuPiD system was well-tolerated and participants found the tool user-friendly.ConclusionCuPiD was feasible, well-accepted and seemed to be an effective approach to promote gait training, as participants improved equally to controls. This benefit may be ascribed to the real-time feedback, stimulating corrective actions and promoting self-efficacy to achieve optimal performance. Further optimization of the system and adequately-powered studies are warranted to corroborate these findings and determine cost-effectiveness.     

The efficacy and safety of ropinirole prolonged release tablets as adjunctive therapy in Chinese subjects with advanced Parkinson's disease: A multicenter,double-blind,randomized, placebo-controlled study

AimThe first evaluation of the efficacy and safety of ropinirole prolonged release (PR) as an adjunct to L-dopa in Chinese patients with advanced Parkinson's disease (PD) not optimally controlled with L-dopa.MethodsIn a 24-week, double-blind, placebo-controlled, parallel-group study, subjects with advanced PD were randomized 1:1 to ropinirole PR (N = 175) or placebo (N = 170) as add-on therapy to L-dopa. Primary outcome measure was change from baseline in awake time spent “off”. Starting dose of ropinirole PR was 2 mg/day, titrated based on clinical response (maximum 24 mg/day).ResultsAt week 24, the mean dose of ropinirole PR was 11.4 mg/day with a mean reduction of L-dopa from 506.6 to 411.6 mg/day. Subjects receiving ropinirole PR experienced a significant reduction of “off” time (2.1 h) compared with placebo (0.4 h). Secondary outcome measures including hours of “on” time without troublesome dyskinesis were significantly increased in the ropinirole PR group (1.7 h) compared with placebo (0.3 h). Subjects classified as responders were significantly more frequent in the ropinirole PR (22.8%) than placebo group (2.5%). Efficacy outcomes including Unified Parkinson's disease Rating Scale and PDQ-39 subscales of mobility were significantly improved in the ropinirole PR versus placebo group. The most frequent adverse event experienced in the ropinirole PR group was dyskinesia.ConclusionsThis study demonstrated for the first time in Chinese subjects that ropinirole PR improved Parkinson's disease symptoms, permitting a reduction in L-dopa dose. The adverse events observed were consistent with the established safety profile of ropinirole, with no new safety signal identified.     

Unsupervised home monitoring of Parkinson's disease motor symptoms using body-worn accelerometers

IntroductionCurrent PD assessment methods have inherent limitations. There is need for an objective method to assist clinical decisions and to facilitate evaluation of treatments. Accelerometers, and analysis using artificial neural networks (ANN), have shown potential as a method of motor symptom evaluation. This work describes the development of a novel PD disease state detection system informed by algorithms based on data collected in an unsupervised, home environment. We evaluated whether this approach can reproduce patient-completed symptom diaries and clinical assessment of disease state.Methods34 participants with PD wore bilateral wrist-worn accelerometers for 4 h in a research facility (phase 1) and for 7 days at home whilst completing symptom diaries (phase 2). An ANN to predict disease state was developed based on home-derived accelerometer data. Using a leave-one-out approach, ANN performance was evaluated against patient-completed symptom diaries and against clinician rating of disease state.ResultsIn the clinical setting, specificity for dyskinesia detection was extremely high (0.99); high specificity was also demonstrated for home-derived data (0.93), but with low sensitivity (0.38). In both settings, sensitivity for on/off detection was sub-optimal. ANN-derived values of the proportions of time in each disease state showed strong, significant correlations with patient-completed symptom diaries.ConclusionAccurate, real-time evaluation of symptoms in an unsupervised, home environment, with this sensor system, is not yet achievable. In terms of the amounts of time spent in each disease state, ANN-derived results were comparable to those of symptom diaries, suggesting this method may provide a valuable outcome measure for medication trials.