Jeffrey Sullivan, Tiffany M. Shih, Emma van Eijndhoven, Yash J. Jalundhwala, Darius N. Lakdawalla, Cindy Zadikoff, Jennifer Benner, Thomas S. Marshall and Kavita R. Sail

# The Social Value of Improvement in Activities of Daily Living among the Advanced Parkinson’s Disease Population

Open Access
De Gruyter | Published online: November 25, 2020

# Abstract

## Objectives

Quantify the value of functional status (FS) improvements consistent in magnitude with improvements due to levodopa-carbidopa intestinal gel (LCIG) treatment, among the advanced Parkinson’s disease (APD) population.

## Methods

The Health Economic Medical Innovation Simulation (THEMIS), a microsimulation that estimates future health conditions and medical spending, was used to quantify the health and cost burden of disability among the APD population, and the value of quality-adjusted life-years gained from FS improvement due to LCIG treatment compared to standard of care (SoC). A US-representative Parkinson’s disease (PD)-comparable cohort was constructed in THEMIS based on observed PD patient characteristics in a nationally representative dataset. APD was defined from the literature and clinical expert input. The PD and APD cohorts were followed from 2010 over their remaining lifetimes. All individuals were ages 65 and over at the start of the simulation. To estimate the value of FS improvement due to LCIG treatment, decreases in activities of daily living (ADL) limitations caused by LCIG treatment were calculated using data from a randomized, controlled, double-blind, double-dummy clinical trial and applied to the APD population in THEMIS.

## Results

Total burden of disability associated with APD was $17.7 billion (B). From clinical trial data, LCIG treatment versus SoC lowers the odds of difficulties in walking, dressing, and bathing by 76%, 42% and 39%, respectively. Among the APD population, these reductions generated$2.6B in value to patients and cost savings to payers. The added value was 15% of the burden of disability associated with APD and offsets 15% of the cost of LCIG treatment.

## Conclusions

FS improvements, consistent with improvements due to LCIG treatment, in the APD population created health benefits and reduced healthcare costs in the US.

## 1 Introduction

### Figure 2:

Change in outcomes from reducing disability due to APD.

B billion, QALY quality-adjusted life year.

Figure 3 provides the effects of LCIG treatment on walking, dressing, and bathing, as estimated from the clinical trial data (Olanow et al. 2014). The effects of LCIG treatment compared to SoC lowered the odds of difficulty in walking, dressing, and bathing by 76%, 43% and 38%, respectively. Table 2 provides the health and cost outcomes resulting from LCIG treatment under the baseline and sensitivity scenarios. When applied simultaneously, reductions in difficulty with walking, dressing, and bathing due to LCIG treatment in the APD cohort generated 15,946 patient life-years, 10,631 QALYs (equivalent to 8.1% of the total life-year burden and 11.8% of the total QALY burden associated with disability due to by APD), and $0.5B in savings in medical expenditures by all payers over the lifetime of all APD patients, relative to SoC. The value of health improvement and cost savings from improving all three ADLs due to LCIG treatment totaled$2.6B in value across all payers and patients relative to SoC. This value was equivalent to 15% of the total disability burden of APD and offset 15% of LCIG treatment costs among the APD population. Medicaid spending decreased by $0.2B, partially due to 3692 fewer patient-years spent by LCIG treated APD patients in nursing homes and 7450 fewer person-years of Medicaid enrollment. ### Figure 3: Odds ratio of experiencing FS limitations for individuals treated with LCIG versus individuals under SoC, based on 12-week clinical trial results. FS functional status, LCIG levodopa-carbidopa intestinal gel, SoC standard of care The clinical trial UPDRS Part II secondary endpoint results were disaggregated and then used to estimate the proportion of subjects with difficulty in each ADL, by treatment arm (Olanow et al. 2014). Specifically, for each ADL, the odds ratio of difficulty for individuals receiving LCIG treatment versus individuals receiving SoC was calculated using the 12-week trial results as follows: Odds ratio = ( Proportion of subjects with limitation , LCIG treatment Proportion of subjects without limitation , LCIG treatment ) ( Proportion of subjects with limitation , SoC Proportion of subjects without limitation , SoC ) . Table 2: The effect of improved activity from LCIG treatment for the APD population relative to SoC. APD classification ADLs Baselined All three Baselined Walking Baselined Dressing Baselined Bathing Sensitivitye All three Health outcomes Patient life-years (not quality-adjusted) 15,954 2,041 12,619 1,448 41,502 QALYs (discounted to 2015) 10,631 4,203 5,030 1,167 26,160 Monetized QALYs (2015$ millions, $200 K/QALY) 2,126 841 1,006 233 5,232 Key expenditure components Nursing home patient-years −3,692 −2,735 −891 −47 −9,431 Medicaid enrollment person-years −7,450 −5,543 −1,395 −770 −19,732 Medicaid expenditures (2015$ millions) −208 −133 −65 −21 −534
Total medical expendituresa (2015$millions) −519 −584 83b −2 −1,274 Total social valuec(2015$ millions) 2,645 1,425 923 236 6,506

ADL activities of daily living, APD advanced Parkinson’s disease, K thousand, QALY quality-adjusted life year.aTotal medical expenditures measured all medical payments made for a patient by all payers, and are not limited to Medicaid expenditures. This measure was obtained directly from survey respondents and was cross-checked using Medicare claims; LCIG treatment cost was not included.bTotal medical expenditures may increase due to increased longevity from improved FS.cChange in total social value is the sum of changes in total medical expenditures and monetized QALYs.dBaseline classification of APD is repeated falls and use of an ambulatory assistance device as measured in the HRS within the PD-comparable cohort.eSensitivity classification of APD first identifies APD as PD with repeated falls and ambulatory assistance device use as observed in the MCBS, then imputes APD status into the HRS based on the characteristics of the APD population in the MCBS.

## 4 Discussion

This study estimated the value of FS improvements that are consistent in magnitude with improvements due to LCIG treatment, over the lifetime of the APD population, using a microsimulation model that predicts long-term economic and health outcomes based on longitudinal transitions in the current population. Results from a randomized, controlled, double-blind, double-dummy clinical trial were leveraged to quantify the effect of LCIG treatment on FS (Olanow et al. 2014). Because the model was parameterized using nationally representative data, the results of the study are generalizable to the broader APD population in the US.

Prior work has shown that the costs of PD are substantial, particularly in the advanced stages. Johnson et al. (2013b) found that in the year following institutionalization or the adoption of an ambulatory assistance device, privately insured PD patients had 6–7 times higher healthcare costs than their non-PD counterparts (Johnson et al. (2013b)). Similarly, Kaltenboeck et al. (2012) showed that Medicare beneficiaries with early and advanced PD experienced higher direct medical costs and mortality than their non-PD counterparts (Kaltenboeck et al. 2012). The current study builds upon this prior work, but also provides new findings by (1) isolating the burden of disability in APD, (2) incorporating impacts on QoL in addition to medical expenditures, and mortality to estimate overall value, and (3) providing value estimates aggregated over a lifetime horizon. The results demonstrated that the disability component of APD alone impose a sizeable economic burden to society, equivalent to $17.7B. This study also found that LCIG treatment can reduce this burden by improving FS. The combined reductions in difficulty in walking, dressing, and bathing due to LCIG treatment generated a total lifetime value of$2.6B for the current APD population in the baseline estimates. Overall, improvement in these three activities reduced the total APD disability burden by 15%. The impact on monetized QALYs due to improvement in FS from LCIG treatment constituted 80% of the overall social value. Reduced total medical expenditures comprised the remaining 20% of the value from improved FS due to LCIG treatment. To characterize contributors to total medical expenditures, impacts of LCIG treatment on nursing home patient-years and Medicaid enrollment and expenditures were estimated over the patients’ lifetimes. The probability of nursing home and Medicaid enrollment both increase for those with three or more ADL limitations. The FS improvement from LCIG treatment therefore decreased total time spent in nursing homes and Medicaid expenditures.

Furthermore, the individual components of value from LCIG treatment were identified. In particular, in the clinical trial results, LCIG treatment had the greatest impact on walking difficulty. As a result, the effect of LCIG treatment on reducing walking difficulty led to the greatest increase in social value among the three individual ADLs analyzed in this study. Improvement in walking and dressing led to similar gains in QALYs, while bathing led to smaller QALY gains. A comparison of the impact on patient life-years versus the impact on QALYs reveals that improvement in walking primarily resulted in improvement in QoL, while improvement in dressing was primarily associated with increases in patient life-years. Since dressing extended life in a relatively poor health states, it also resulted in higher medical spending. As a result of these factors, the overall value from improved dressing was lower than the value from improved walking. The analysis of individual ADLs thereby revealed that walking improvement were the key driver of the value of LCIG treatment.

There are some limitations to this study. First, PD status could not be directly observed in the HRS data. As a result, a PD cohort was imputed based on characteristics (demographics and ADLs) of the observed PD population in the MCBS. This imputation may not perfectly identify PD patients, thus creating error in our estimates. A sensitivity analysis was performed defining APD directly within the observed PD population in the MCBS data, and APD status was imputed into the HRS data to be utilized in THEMIS. Relative to the baseline results, the absolute burden of disability due to APD and value of improved FS due to LCIG treatment both increased in the sensitivity analysis. However, the proportion of the APD burden alleviated by LCIG treatment decreased slightly, from 15 to 13%.

Second, the FS questionnaire in the clinical trial differed from that used in the HRS data. As a result, a restricted set of ADLs was included in the analysis, which may omit important FS determinants of value. For example, prior research has found that difficulty eating may also be influential in outcomes for the elderly population (Fong, Mitchell, and Koh 2015). Furthermore, we were only able to capture binary changes between any difficulty versus no difficulty in ADLs in THEMIS, so that actual LCIG treatment may lead to additional benefits from reductions in the severity of difficulty.

Third, a challenge was to properly define APD in order to estimate social value for this population. While there is no single definition of APD agreed upon by clinicians, for this study the definition of having both repeated falls and being unable to walk unassisted was used, based on clinical expert input and the results of a Delphi panel of movement disorder specialists, which was conducted to identify primary characteristics of APD patients (Antonini et al. 2015). However, estimates of the value of improved FS within the APD population may change under an alternative definition of APD.

Fourth, ADL limitations affect multiple health outcomes beyond the endpoints in this study. ADL limitations were included in the transition models of different health outcomes when the literature showed them to be a predictor of the health outcome. However, this correlation between ADL limitations and health outcomes might be due to unobserved factors. As the value of LCIG treatment is measured through its effect on ADL limitations, these other associations might lead to an overestimation of the social value of LCIG treatment.

Lastly, the current version of THEMIS does not yet have the capability to compute confidence intervals around simulation estimates. There are many sources of uncertainty in the model, since many of the transition models are based on regression estimates. This means we are unable translate the variation around a particular parameter directly into variation of the output.

## 5 Conclusion

This study found that disability due to APD imposes a substantial economic burden on society through its effects on lifespan, QoL, and medical expenditures among the APD population. Reduced limitations in FS that are of a magnitude consistent with LCIG treatment, improved health outcomes and reduced healthcare costs for APD patients in the US over their lifetimes. Future research should consider the comprehensive effect of APD treatments in reducing NHA risk and social value, incorporating its effects on a broader set of ADLs and IADLs, and should perform further sensitivity analyses around the definition of APD.

Funding source: AbbVie

# Acknowledgments

We would like to thank Suepattra May-Slater, employee of PRECISIONheor, and Warren Stevens and Shalak Gunjal, former employees of PRECISIONheor, for their support of this study. Financial support for their services was provided by AbbVie.

Declaration of funding: This study and manuscript were funded by AbbVie. The design, study conduct, and financial support for the study were provided by AbbVie. AbbVie participated in the study design, research, interpretation of data, writing, reviewing, and approving the manuscript. No honoraria or payments were made for authorship.

Declaration of financial/other relationships: Kavita Sail and Yash J. Jalundhwala are employees of AbbVie and may own AbbVie stock or stock options. Thomas Marshall was an employee of AbbVie at the time of the study and may own AbbVie stock or stock options. Jeffrey Sullivan and Emma van Eijndhoven are employees of PRECISIONheor. Jennifer Benner and Tiffany Shih were employees of PRECISIONheor at the time of the study. PRECISIONheor is part of Precision for Medicine Group, which receives compensation from various biopharmaceutical companies, including AbbVie. Darius N. Lakdawalla holds equity in Precision Medicine Group. Cindy Zadikoff currently is an employee of AbbVie and may own AbbVie stock or stock options. When the study was being conducted, Cindy Zadikoff was affiliated with Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States and has previously received honoraria for consulting and lecturing from AbbVie. In addition, she has received consulting honoraria from various biopharmaceutical companies.

Appendix

Appendix Table 1:

Advanced Parkinson’s disease model in the MCBS used to impute into the HRS (sensitivity identification strategy).

Coefficient SE
Race
Black 0.282 0.230
Hispanic −0.585** 0.264
Education
Less than high school −0.085 0.150
Some college and above 0.097 0.155
Male 0.008 0.133
Functional status
Two-year lag of difficulty with walking 0.489*** 0.151
Two-year lag of difficulty with dressing 0.136 0.183
Two-year lag of difficulty getting out of bed and a chair 0.195 0.167
Two-year lag of difficulty using the telephone 0.116 0.164
Two-year lag of difficulty handling money 0.286* 0.164
Two-year lag of difficulty using the toilet 0.248 0.210
Two-year lag of currently smoking −0.115 0.248
Two-year lag of being widowed −0.027 0.147
BMI
Two-year lag of underweight: bmi <18.5 kg/m2 0.419 0.536
Two-year lag of overweight: bmi 25–30 kg/m2 −0.210 0.140
Two-year lag of obese: bmi ≥30kg/m2 −0.038 0.171
Age
Two-year lag of ages 65 and-younger −0.008 0.017
Two-year lag of ages 65–74 0.036 0.027
Two-year lag of ages 65 and older 0.013 0.014
Constant −0.710 1.015

BMI body mass index, SE standard error.

### Appendix Figure 1:

Study design flow chart

APD advanced Parkinson’s disease, FS functional status, HRS Health and Retirement Study, MCBS Medicare Current Beneficiary Survey, PD Parkinson’s disease, QALYs quality-adjusted life-years, RCT randomized controlled trial; THEMIS The Health Economics Medical Innovation Simulation

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