Economic Burden of Parkinson's Disease: A Multinational, Real-World, Cost-of-Illness Study.

BACKGROUND: Parkinson's disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients' quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers. OBJECTIVE: We aimed to quantify the incremental economic burden of Parkinson's disease by disease severity in a real-world setting across differing geographic regions. METHODS: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson's Disease Specific Program™, conducted in the USA, five European countries, and Japan. RESULTS: A total of 563 neurologists provided data for 5299 individuals with Parkinson's disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs. CONCLUSIONS: People with Parkinson's disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson's disease and their caregivers, whilst also substantially impacting societal costs.

The value of treatment for infertility: A systematic literature review of willingness-to-pay thresholds and approaches for determining the cost effectiveness of fertility therapies.

Willingness to pay (WTP) for an infertility treatment is the maximum amount of money a patient is willing to pay per treatment, or to achieve a live birth or pregnancy. Such thresholds are important to determine the cost effectiveness of a treatment. A systematic review was conducted to identify and explore the studies that attempt to ascertain WTP for infertility and compare them with the cost-effectiveness studies that claimed to use WTP thresholds. For comparison, all the costs were converted and inflated to 2021 euros. The results demonstrated that there were no standard outcomes or WTP thresholds for an outcome/treatment, and the methodologies used vary. Cost-effectiveness studies either used the incremental cost-effectiveness ratio to imply a WTP threshold, or used thresholds that were previously accepted for a quality-adjusted life year outcome converted, inappropriately, to an infertility outcome. There is a need for further research by health economists to develop a consensus for the meaningful assessment of WTP for ART.

Impact of advanced Parkinson's disease on caregivers: an international real-world study.

BACKGROUND: Caring for a partner or family member with Parkinson's disease (PD) negatively affects the caregiver's own physical and emotional well-being, especially those caring for people with advanced PD (APD). This study was designed to examine the impact of APD on caregiver perceived burden, quality of life (QoL), and health status. METHODS: Dyads of people with PD and their primary caregivers were identified from the Adelphi Parkinson's Disease Specific Program (DSP™) using real-world data from the United States, Japan and five European countries. Questionnaires were used to capture measures of clinical burden (people with PD) and caregiver burden (caregivers). RESULTS: Data from 721 patient-caregiver dyads in seven countries were captured. Caregivers had a mean age 62.6 years, 71.6% were female, and 70.4% were a spouse. Caregivers for people with APD had a greater perceived burden, were more likely to take medication and had lower caregiver treatment satisfaction than those caring for people with early or intermediate PD; similar findings were observed for caregivers of people with intermediate versus early PD. Caregivers for people with intermediate PD were also less likely to be employed than those with early PD (25.3% vs 42.4%) and spent more time caring (6.6 vs 3.2 h/day). CONCLUSIONS: This real-world study demonstrates that caregivers of people with APD experience a greater burden than those caring for people with early PD. This highlights the importance of including caregiver-centric measures in future studies, and emphasizes the need for implementing treatments that reduce caregiver burden in APD. TRIAL REGISTRATION: N/A.

Evaluating the quality of the economic evidence in colorectal cancer genomics studies.

The increase in the use of genome-based screening and diagnostic tests adds to the overall costs of oncologic care for colorectal cancer. This, in turn, has resulted in an increase in published economic analyses. Aim: To perform a systematic literature review of the available economic evidence evaluating the value of genomic testing for colorectal cancer and appraise the quality of the economic studies conducted to date. Methods: A systematic review of the literature for economic studies of colorectal cancer genomics from January 2006 through October 2020, and evaluation of study quality using the Quality of Health Economic Studies (QHES) instrument was conducted. The validated QHES was then applied to a final set of articles that met eligibility criteria. Results: Our search of the literature initially yielded 12,859 records. A final set of 49 articles met our inclusion criteria. The QHES score ranged from 24 to 100, with an average score of 82. Most of the studies (n = 40, 82%) scored above 75 and were considered of good quality. Conclusion: Our analysis revealed that most of the economic analyses of colorectal cancer genomic molecular diagnostics in the literature may be of good quality. There is, however, some variation in methodological rigor between the articles.

Cost-effectiveness of precision molecular diagnostic tests for stage II colorectal cancer.

Background: In colorectal cancer, inappropriate use of adjuvant chemotherapies may lead to significant increases in healthcare costs and harms to patients. Genome-based interventions are being increasingly used in the stratification of patients according to their risk profiles. However, earlier cost-effectiveness analyses of precision molecular diagnostics have indicated a paucity of data on comparative health economic outcomes. Our aim was to compare the cost-effectiveness of marketed genomic tests used in the prognosis of stage II colorectal cancer patients. Methods: A Markov model was developed to compare the cost-effectiveness of treatment guided by any one of the following genomic tests: 12-gene assay or the 18-gene expression assay or the 482-gene signature or the Immunoscore assay in a hypothetical cohort of patients (n=1,000) with stage II colorectal cancer. Our study investigated outcomes in three health states: no recurrence, recurrence and death. This study was conducted from a societal perspective, and a 3% discount was applied to the costs and health outcomes. Sensitivity analyses were performed to assess the uncertainty of model parameters on the results. Results: The cost of the Immunoscore assay strategy in stage II colorectal cancer patients was estimated to be US $23,564 with a gain of 3.903 quality-adjusted life years (QALYs) as compared with the 12-gene assay strategy at US $24,545 and 3.903 QALYs; the 18-gene assay strategy at US $28,374 and 3.623 QALYs; and the 482-gene signature treatment strategy at US $33,315 with 3.704 QALYs. Sensitivity analyses indicated that incremental cost-effectiveness ratio (ICER) values were sensitive to costs of genomic tests and adjuvant chemotherapies; and utilities related to patients in the no-recurrence health state. Conclusions: Overall, the Immunoscore assay seems to be a dominant strategy at a threshold willingness-to-pay of $50,000 per QALY, but in the US other tests have been used for longer. Thus, the 12-gene assay may generate cost savings compared to the 18-gene expression assay. The findings of our study may provide useful information to policymakers regarding selection of the most appropriate genomic test, and resource allocation decisions.

Patterns of Daily Motor-Symptom Control with Carbidopa/Levodopa Enteral Suspension Versus Oral Carbidopa/Levodopa Therapy in Advanced Parkinson's Disease: Clinical Trial Post Hoc Analyses.

INTRODUCTION: A clinical trial in advanced Parkinson's disease (APD) has established the superiority of carbidopa/levodopa enteral suspension (CLES) in reducing total patient "off" time (OFF) and increasing total "on" time without troublesome dyskinesia (ON-woTD) over orally administered immediate-release carbidopa/levodopa tablets (IR-CL). However, temporal patterns of these improvements throughout the waking day have not been examined. In this analysis, time to ON-woTD after waking and patterns of motor-symptom control throughout the waking day were compared between CLES and IR-CL. METHODS: Post hoc analyses of APD patient-diary data from the phase 3 randomized controlled trial were used to compare changes in time to ON-woTD after waking, motor-symptom control throughout the waking day, occurrence of extreme fluctuations between OFF and "on" with troublesome dyskinesia, and motor-state transitions with CLES versus IR-CL from baseline to week 12. RESULTS: The sample included 33 CLES-treated and 30 IR-CL-treated patients. Among the CLES group, the percentage of patient days achieving ON-woTD within 30 min of waking was three times higher at week 12 versus baseline (33% vs. 11%, p = 0.0043); no significant change occurred with IR-CL. When the waking day was divided into four 4-h periods, CLES versus IR-CL treatment produced significantly greater reductions in OFF during three periods, and two periods had increased ON-woTD. Fewer CLES-treated patients had extreme fluctuations at week 12 (3% vs. 23%, p = 0.0224) compared to IR-CL-treated patients. From baseline to week 12, CLES-treated patients had greater reductions in the average number of motor-state transitions compared to IR-CL-treated patients (- 1.6, p = 0.0295). CONCLUSION: CLES-treated patients experienced a more rapid onset of ON-woTD after waking and greater consistency of ON-woTD throughout their waking day than IR-CL-treated patients.

In advanced Parkinson's disease, patients' motor-symptom states (such as "on" time without troublesome dyskinesia [good "on" time] and "off" time), and the timing at which they occur, can impact patients' quality of life and ability to complete activities of daily living. Carbidopa/levodopa enteral suspension is administered continuously into the jejunum, potentially reducing some of the motor-state variation that is common with orally administered carbidopa/levodopa, including delayed "on" time after waking and transitions between "off" and "on" throughout the day. In post hoc analyses of clinical trial data, patterns of motor-states across the waking day were compared between carbidopa/levodopa enteral suspension and orally administered immediate-release carbidopa/levodopa at week 12. Outcomes included time to good "on" after waking; occurrence of extreme fluctuations between "off" time and "on" time with troublesome dyskinesia; time in each motor-state during 4-h intervals across the day; and frequency of motor-state transitions. Three times as many carbidopa/levodopa enteral suspension-treated patients achieved good "on" within 30 min of waking after 12 weeks versus baseline, whereas no significant change was observed for the orally administered immediate-release carbidopa/levodopa group. Compared to orally administered immediate-release carbidopa/levodopa-treated patients, fewer carbidopa/levodopa enteral suspension-treated patients experienced extreme fluctuations, had greater reductions in motor-state transitions, and greater reductions in duration of "off" during three of the four intervals in the day. These findings provide a first look at the impact of carbidopa/levodopa enteral suspension on motor-state patterns throughout the day, and suggest that carbidopa/levodopa enteral suspension provides more consistent motor-symptom control and predictable benefit throughout the day than orally administered carbidopa/levodopa.

The value of multigene predictors of clinical outcome in breast cancer: an analysis of the evidence.

OBJECTIVE: Multigene predictors are being used increasingly in early-stage breast cancer patients for prediction and prognosis. However, one consequence of the increased use of multigene predictors, and the heightened efforts toward their incorporation into routine clinical practice, is the potential for future malpractice litigation. It is, therefore, important to ascertain the strength of the evidence for using the different commercially available multigene predictor assays clinically. We evaluated the literature for evidence of clinical validity of four currently available gene signatures and to assess the influence of the 21-gene-expression assay on changes in treatment recommendations. METHODS: A systematic search of the peer-reviewed literature from January 2002 to March 2014 for multigene predictor assays was carried out, and a meta-analysis was conducted. RESULTS: The adjusted Cox hazard ratio average for studies that met the eligibility criteria was 3.538 (95% CI: 1.513-8.469). The 21-gene signature showed the highest stability in the estimation of likelihood of distant risk of recurrence. Using the recurrence scores resulted in changes in treatment recommendations in 31.8% of all patients in the studies. CONCLUSION: This study may provide insight about the use of multigene predictors in clinical practice for prediction and prognosis of breast cancer.