Cost-effectiveness analysis of disease modifiying drugs (interferons and glatiramer acetate) as first line treatments in remitting-relapsing multiple sclerosis patients

Abstract

Objective:

The aim of this study was to assess cost-effectiveness of the different Disease Modifying Drugs (DMD) used as first-line treatments (interferons IM IFNβ-1a, SC IFNβ-1a, SC IFNβ-1b, and glatiramer acetate, GA) in Remitting-Relapsing Multiple Sclerosis (RRMS) in Spain.

Methods:

A Markov model was developed to simulate the progression of a cohort of patients with RRMS, during a period of 10 years. Seven health states, defined by the Expanded Disability Status Scale (EDSS), were considered in the model. Patients with an EDSS score less than 6.0 were assumed to be treated with one of the DMD. In addition, all patients were assumed to receive symptomatic treatment. The monthly transition probabilities of the model were obtained from the literature. The analysis was performed from the societal perspective, in which both direct and indirect (losses in productivity) healthcare costs (€, 2010) were included. A discount rate of 3% was applied to both costs and efficacy results.

Results:

GA was the less costly strategy (€322,510), followed by IM IFNβ-1a (€329,595), SC IFNβ-1b (€ 333,925), and SC IFNβ-1a (€348,208). IM IFNβ-1a has shown the best efficacy results, with 4.176 quality-adjusted life years (QALY), followed by SC IFNβ-1a (4.158 QALY), SC IFNβ-1b (4.157 QALY), and GA (4.117 QALY). Incremental costs per QALY gained with IM IFNβ-1a were €?1,005,194/QALY, €?223,397/QALY, and €117,914/QALY in comparison to SC IFNβ-1a, SC IFNβ-1b, and GA, respectively.

Conclusions:

First-line treatment with GA is the less costly strategy for the treatment of patients with RRMS. Treatment with IM IFNβ-1a is a dominant strategy (lower cost and higher QALY) compared with SC IFNβ-1a and SC IFNβ-1b. However, IM IFNβ-1a is not a cost-effective strategy vs GA, because incremental cost per QALY gained with IM IFNβ-1a exceeds the €30,000 per QALY threshold commonly used in Spain.

Limitations:

The highly-restrictive inclusion criteria of clinical trials limits generalization of the results on efficacy to all patients with multiple sclerosis. Availability of data for head-to-head comparisons is associated with the use of information from clinical trials.     

Cost effectiveness of teriparatide and PTH(1-84) in the treatment of postmenopausal osteoporosis

Abstract

Objectives:

The purpose was to assess the cost effectiveness from a societal perspective of the recombinant human parathyroid hormones: PTH(1-34) (teriparatide) and PTH(1-84) for patients with osteoporosis with similar characteristics to patients treated in normal clinical practice in Sweden.

Methods:

A Markov model of osteoporosis in postmenopausal women was developed using 6-month cycles and a lifetime horizon. The model was populated with patients similar to the Swedish cohort of the European Forsteo Observational Study (postmenopausal women; mean age: 70 years, total hip T-score: ?2.7 and 3.3 previous fractures). The cost effectiveness of both teriparatide and PTH(1-84) was estimated compared to no treatment and each other. Relative effectiveness assumptions were based on efficacy estimates from two phase III clinical trials.

Results:

The cost per QALY gained of teriparatide vs. no treatment was estimated at €43,473 and PTH(1-84) was estimated at €104,396. Teriparatide was indicated to be less costly and associated with more life-years and QALYs than PTH(1-84). When assuming no treatment effect on hip fractures the cost per QALY gained was €88,379. In the sensitivity analysis the cost effectiveness did not alter substantially with changes in the majority of the model parameters except for the residual effect of the treatment after stopping therapy.

Conclusions:

Based on the efficacy estimates from pivotal clinical trials and characteristics of patients treated in clinical practice in Sweden, teriparatide seems to be a more cost-effective option than PTH(1-84) when compared to no treatment. The relative efficacy between the two PTH compounds was based on an indirect comparison from two separate clinical trials which has to be considered when interpreting the results.     

Implications of Real-world Adherence on Cost-effectiveness Analysis in Multiple Sclerosis

Abstract

Objectives:

Adherence to medication is essential for optimal outcomes, especially for chronic diseases such as multiple sclerosis (MS). Studies in MS indicate that lower adherence is associated with an increased risk of relapse, hospitalization or emergency room (ER) visits, and higher medical costs. A previous investigation assessed the cost per relapse avoided for patients with MS receiving first-line disease modifying therapies (DMTs); however, the model assumed 100% adherence.

Methods:

Because real-world utilization patterns influence the actual effectiveness of medications, this analysis assessed the impact of real-world adherence from a US commercial payer perspective, using updated costs.

Results:

As was seen in the original study, in this revised model, fingolimod was associated with the lowest cost per relapse avoided ($90,566), followed by SC IFN β-1b (Extavia: $127,024), SC IFN β-1b (Betaseron: $137,492), SC IFN β-1a ($144,016), glatiramer acetate ($160,314), and IM IFN β-1a ($312,629). The model inputs that had the greatest impact on the results were adherence-adjusted relative relapse rate reduction (RRR) of fingolimod, the wholesale acquisition costs of fingolimod, and the average number of relapses in untreated patients with MS.

Limitations:

The estimates of DMT adherence are from a single claims database study of a large national pharmacy benefit manager that only measured adherence, not actual relapses, and the model does not incorporate manufacturer discounts and rebates, which are not publicly available.

Conclusion:

These results suggest that economic analyses of MS therapies should incorporate real-world adherence rates where available, rather than relying exclusively on trial-based efficacy estimates when considering the economic value of treatment alternatives, and that highly efficacious therapies with low adherence may yield real-world efficacy that is substantially lower than that observed in closely monitored clinical trials.     

Corrigendum to “On randomized matching mechanisms” [Economic Theory 8(1996)377–381]

Ma (in Econ. Theory 8, 377–381, 1996) studied the random order mechanism, a matching mechanism suggested by Roth and Vande Vate (Econometrica 58, 1475–1480, 1990) for marriage markets. By means of an example he showed that the random order mechanism does not always reach all stable matchings. Although Ma's (1996) result is true, we show that the probability distribution he presented – and therefore the proof of his Claim 2 – is not correct. The mistake in the calculations by Ma (1996) is due to the fact that even though the example looks very symmetric, some of the calculations are not as “symmetric.” We thank two anonymous referees for their helpful comments. B. Klaus’s and F. Klijn’s research was supported by Ramón y Cajal contracts of the Spanish Ministerio de Ciencia y Tecnología. The work of the authors was also partially supported through the Spanish Plan Nacional I+D+I (BEC2002-02130 and SEJ2005-01690) and the Generalitat de Catalunya (SGR2005-00626 and the Barcelona Economics Program of CREA).     

Cost-effectiveness of novel relapsed-refractory multiple myeloma therapies in Norway: lenalidomide plus dexamethasone vs bortezomib

Abstract

Objective:

To estimate the cost-effectiveness (cost per additional life-year [LY] and quality-adjusted life-year [QALY] gained) of lenalidomide plus dexamethasone (LEN/DEX) compared with bortezomib for the treatment of relapsed-refractory multiple myeloma (rrMM) in Norway.

Methods:

A discrete-event simulation model was developed to predict patients’ disease course using patient data, best response, and efficacy levels obtained from LEN/DEX MM-009/-010 trials and the bortezomib (APEX) published clinical trial. Predictive equations for time-to-progression (TTP) and post-progression survival (PPS) were developed by identifying the best fitting parametric survival distributions and selecting the most significant predictors. Disease and adverse event management was obtained via survey from Norwegian experts. Costs, derived from official Norwegian pricing data bases, included drug, administration, monitoring, and adverse event management costs.

Results:

Complete or partial responders were 65% for LEN/DEX compared to 43% for bortezomib. Derived median TTP was 11.45 months for LEN/DEX compared to 5.15 months for bortezomib. LYs and QALYs were higher for LEN/DEX (4.06 and 2.95, respectively) than for bortezomib (3.11 and 2.19, respectively). The incremental costs per QALY and LY gained from LEN/DEX were NOK 247,978 and NOK 198,714, respectively, compared to bortezomib. Multiple sensitivity analyses indicated the findings were stable. The parameters with the greatest impact were 4-year time horizon (NOK 441,457/QALY) and higher bound confidence intervals for PPS (NOK 118,392).

Limitations:

The model analyzed two therapies not compared in head-to-head trials, and predicted results using an equation incorporating patient-level characteristics. It is a limited estimation of the costs and outcomes in a Norwegian setting.

Conclusions:

The simulation model showed that treatment with LEN/DEX leads to greater LYs and QALYs when compared to bortezomib in the treatment of rrMM patients. The incremental cost-effectiveness ratio indicated treatment with LEN/DEX to be cost-effective and was the basis of the reimbursement approval of LEN/DEX in Norway.     

A comparison of work absence periods and the associated costs for two different modes of exercise therapies for patients with longstanding subacromial pain

Abstract

Background: There are no studies on economic issues concerning rehabilitation exercises for shoulder pain.

Objective: The aim of the study was to investigate sick leave and the associated costs after a medical exercise therapy programme in patients with longstanding subacromial pain/impingement.

Methods: A randomised controlled trial in which 61 patients were randomly assigned either to a high-dosage medical exercise therapy group (HD) (n=31) or to a low dosage exercise therapy group (LD) (n=30). Both groups were given three treatments a week over 3 months. The differences between the groups were number of repetitions, number of sets and time performing global aerobic exercises.

Results: The outcome for the HD group was significantly (p<0.05) better compared to the LD group. The reduction in costs for sick leave for the HD group was 59.1%, whereas for the LD group, the reduction was only 42.3%, which is a significant difference.

Conclusion: In patients with longstanding subacromial pain, HD medical exercise therapy might be an efficient treatment approach.     

Comparison of hospital length of stay and hospitalization costs among patients with non-valvular atrial fibrillation treated with apixaban or warfarin: An early view

Objective: To quantify and compare hospital length of stay (LOS) and costs between hospitalized non-valvular atrial fibrillation (NVAF) patients treated with either apixaban or warfarin via a large claims database.

Methods: Adult patients hospitalized with AF were selected from the Premier Perspective Claims Database (01JAN2013-31MARCH2014). Patients with evidence of valvular heart disease, valve replacement procedures, or pregnancy during the index hospitalization were excluded. Patients treated with apixaban or warfarin during hospitalization were identified. Propensity score matching (PSM) was performed to control for baseline imbalances between patients treated with apixaban or warfarin. Primary outcomes were hospital LOS (days), post-medication administration LOS, and index hospitalization costs, and were compared using paired t-tests in the matched sample.

Results: Before PSM, 2894 apixaban and 124,174 warfarin patients were identified. Patients treated with warfarin were older and sicker compared to those treated with apixaban. After applying PSM, a total of 2886 patients were included in each cohort, and baseline characteristics were balanced. The mean (standard deviation [SD] and median) hospital LOS was significantly (p?=?0.002) shorter for patients treated with apixaban for 5.1 days (5.7 and 3) compared to warfarin for 5.5 days (4.8 and 4). The trend appeared consistent in the hospital LOS from point of apixaban or warfarin administration to discharge (4.5 vs 4.7 days, p?=?0.051). Patients administered apixaban incurred significantly lower hospitalization costs compared to those administered warfarin ($11,262 vs $12,883; p?<?0.001).

Conclusions: Among NVAF patients, apixaban treatment was associated with significantly shorter hospital LOS and lower costs when compared to warfarin treatment.     

Respiratory-related medical expenditure and inpatient utilisation among COPD patients receiving long-acting bronchodilator therapy

Abstract

Objective:

To evaluate chronic obstructive pulmonary disease (COPD)-related expenditure and hospitalisation in COPD patients treated with tiotropium versus alternative long-acting bronchodilators (LABDs).

Methods:

Data were from the Thomson Reuters MarketScan Research Databases. COPD patients ≥35 years with at least one LABD claim between July 1, 2004 and June 30, 2006 were classified into five cohorts based on index LABD: monotherapy with tiotropium, salmeterol/fluticasone propionate, formoterol fumarate, or salmeterol or combination therapy. Demographic and clinical characteristics were evaluated for a 6-month pre-period and COPD-related utilisation and total costs were evaluated for a 12-month follow-up period. LABD relationship to COPD-related costs and hospitalisations were estimated by multivariate generalised linear modelling (GLM) and multivariate logistic regression, respectively.

Results:

Of 52,274 patients, 53% (n?=?27,457) were male, 71% (n?=?37,271) were ≥65?years, and three LABD cohorts accounted for over 90% of the sample [53% (n?=?27,654) salmeterol/fluticasone propionate, 23% (n?=?11,762) tiotropium, and 15% (n?=?7755) combination therapy]. Patients treated with salmeterol/fluticasone propionate (p?<?0.001), formoterol fumarate (p?=?0.032), salmeterol (p?=?0.004), or with combination therapy (p?<?0.001) had higher COPD-related costs and a greater risk of inpatient admission (p?<?0.01 for all) versus tiotropium.

Limitations:

These data are based on administrative claims and as such do not include clinical information or information on risk factors, like smoking status, that are relevant to this population.

Conclusions:

Patients treated with tiotropim had lower COPD-related expenditures and risk of hospitalisation than patients treated with other LABDs     

Cost effectiveness of asthma treatment with a breath-actuated inhaler: how has the story changed?

Abstract

Objectives: A database analysis evaluating the comparative costs and outcomes of asthma treatment with breath-actuated inhalers (BAIs) and metered-dose inhalers (MDIs) has previously been undertaken in 2001. This analysis found that, despite the higher acquisition cost associated with BAIs, economies elsewhere meant that the overall cost associated with BAIs was lower than MDIs. Between 2001 and 2007, the comparative price of MDIs was significantly reduced thus widening the gap between the comparative acquisition cost of MDIs and BAIs. Furthermore, the introduction of specific targets for asthma review included a requirement for regular checks on inhaler technique. Such initiatives may be expected to enhance the overall effectiveness of MDIs. Given the potential impact of such changes, it appeared to be timely to update the original database analysis to assess the extent to which the original findings have been altered by changes in the clinical and economic environment over the past 5 years.

Methods: As in all chronic diseases, it is important that economic analyses evaluate cost effectiveness over as long a period as possible, and so the 2006 analysis was conducted over a 12- and a 24-month time period.

Results: The results emphasised that the clinical benefits associated with BAIs for certain patients can still be translated into greater cost effectiveness, but that altered cost structures required a longer time period for the greater cost effectiveness of BAIs to become evident.

Conclusion: Since completing this study, the reimbursement costs for beclometasone MDIs have increased significantly (since October 2007) due to the discontinuation of Becotide and Becloforte. As a consequence of this higher acquisition cost for MDI inhalers, the current cost-effectiveness advantages of BAI compared to MDI can be expected to be even greater than that identified in the study.     

Cost-minimization comparison of darunavir plus ritonavir and lopinavir/ritonavir in HIV-1 infected treatment-naïve women of childbearing age

Background:

Guidelines from the Department of Health and Human Services in the US recommend ritonavir-boosted lopinavir (LPV/r) as a preferred protease inhibitor (PI) for HIV-positive antiretroviral-na?ve pregnant women. These guidelines also cite ritonavir-boosted darunavir (DRV?+?RTV) as an alternative PI in this clinical scenario. The purpose of this analysis was to compare economic outcomes for regimens based on these two treatments.

Study design:

An existing discrete event simulation (DES) model was adapted to conduct a cost-minimization analysis comparing the two regimens in HIV-infected women of childbearing age (WOCBA), from the perspective of a healthcare payer in the US.

Methods:

The DES model was used to represent disease states, health events, healthcare encounters, pregnancy, and treatment choices in HIV-infected WOCBA starting treatment with regimens based on either LPV/r or DRV?+?RTV. It also incorporated parameters for individual patient characteristics, and for antiretroviral (ARV) treatment effectiveness, treatment sequencing, clinical progression, and resource use. Potential events included scheduled physician visits; viral suppression; viral rebound; AIDS-related complications; CHD events; treatment discontinuation and switching; ARV treatment side-effects (SE); and death. The primary outcomes were discounted 5-year and 10-year healthcare costs. Alternative scenarios considered different rates of switching from DRV?+?RTV to LPV/r upon conception.

Results:

Compared with DRV?+?RTV, LPV/r was associated with similar clinical outcomes while offering savings at the 5- and 10-year horizons (of $24,904 and $43,502 per patient, respectively), and in extensive sensitivity analyses. The main driver of the savings was the difference in cost between PIs.

Conclusions:

Starting HIV-infected ARV-treatment-na?ve WOCBA on an LPV/r-based regimen is cost-saving and provides similar patient outcomes compared to a DRV?+?RTV-based regimen.     

Medical resource use and costs associated with chylomicronemia

Abstract

Background:

The prevalence of severe hypertriglyceridemia (TG?>?1000?mg/dl) is estimated at 150–400 per 100,000 individuals in North America. Severe hypertriglyceridemia in the fasting state is associated with increased acute pancreatitis risk and is a sign of chylomicronemia which reflects the accumulation in the bloodstream of chylomicrons, the large lipoprotein particles produced in the gut after a meal.

Objective:

To assess medical resource use and costs associated with chylomicronemia.

Methods:

Patients with chylomicronemia of different causes (≥2 diagnoses with ICD-9 code 272.3) were identified from a large US claims database (years 2000 to 2009) and matched 1:1 to controls free of chylomicronemia based on age, gender, demographics, comorbidities, and use of lipid lowering drugs. During a 1-year study period, medical resource use and costs associated with chylomicronemia or acute pancreatitis were compared between matched cases and controls.

Results:

Among 6472 matched pairs, annual per-patient medical costs, calculated independently of the occurrence of acute pancreatitis, were significantly greater by $808 for chylomicronemia cases vs controls ($8029 vs $7220, p?<?0.01), half of which was attributable to chylomicronemia-related services (p?<?0.01). Chylomicronemia cases with a history of acute pancreatitis (n?=?46) had greater rates of inpatient visits (p?<?0.05) and greater average costs for subsequent acute pancreatitis or abdominal pain (p?<?0.01) as well as greater total medical costs ($33,587 vs $4402, p?<?0.01) vs matched controls. The average episode of acute pancreatitis (n?=?104 episodes) generated medical costs of $31,820, almost entirely due to inpatient stays.

Limitations:

Triglyceride levels were not available to characterize disease severity.

Conclusions:

Patients with chylomicronemia, and especially those with a history of acute pancreatitis, incurred significantly greater total medical costs compared with individuals without chylomicronemia but with an otherwise comparable health profile.     

Humanistic and economic impacts of hepatitis C infection in the United States

Abstract

Objective:

Prior research examining the effect of hepatitis C virus (HCV) on health-related quality of life (HRQoL) and healthcare costs is flawed because non-patient controls were not adequately comparable to HCV patients. The current study uses a propensity score matching methodology to address the following research question: is the presence of diagnosed hepatitis C (HCV) associated with poorer health-related quality of life (HRQoL) and greater healthcare resource use?

Methods:

Using data from the 2009 US National Health and Wellness Survey, patients who reported a HCV diagnosis (n?=?695) were compared to propensity-matched controls (n?=?695) on measures of HRQoL and healthcare resource use. All analyses applied sampling weights to project to the US population.

Results:

HCV patients reported significantly lower levels of HRQoL relative to the matched-control group, including the physical component score (39.6 vs. 42.7, p?<?0.0001) and health utilities (0.63 vs. 0.66, p?<?0.0001). The number of emergency room visits (0.59 vs. 0.44, p?<?0.05) and physician visits (7.7 vs. 5.9, p?<?0.05) in the past 6 months were significantly higher for the HCV group relative to matched controls.

Conclusion:

The results of this study suggest that HCV represents a substantial burden on patients by having a significant and clinically-relevant impact on key dimensions of HRQoL as well as on utilization of healthcare resources, the latter of which would result in increased direct medical costs.

Limitations:

Due to limitations of the internet survey approach (e.g., inability to confirm HCV diagnosis), future research is needed to confirm these findings.     

Hospital patients with severe wounds: early evidence on the impact of Medicare payment changes on treatment patterns and outcomes

Aims: This study examines the effects of recent changes in Medicare long-term care hospital (LTCH) payments on treatment patterns and outcomes for severe wound patients discharged from short-term acute care hospitals (STACHs).

Materials and methods: The rolling implementation of a new Medicare payment policy was used to develop a difference-in-difference model. The study population consisted of Medicare beneficiaries subjected to the payment policy changes and hospitalized for stage 3, 4, or unstageable wounds; non-healing surgical wounds; and fistula. Using 2015-Q1-2017 Medicare claims data, changes in outcomes were examined for severe wound patients exposed to the new policy (treatment) and those that were not (comparison). All outcomes were modeled using linear regressions and adjusted for patient clinical characteristics. Analysis was conducted in a full sample and a sample with high-LTCH-use propensity.

Results: Severe wound patients exposed to the new policy experienced 4.1 and 7.5 percentage point (pp) reductions in LTCH use relative to the comparison group in the full sample and high-LTCH-propensity sample, respectively (p?p?=?.039). No statistically significant change was found in 60-day mortality or Medicare spending after the policy change in the treatment group as compared to the comparison group (p?>?.10). However, among severe wound patients who are exposed to the new policy in the high-LTCH-propensity sample, readmission and post-discharge sepsis rates increased after the policy change relative to the comparison group (readmission rate = 8.1 pp, p?=?.075; sepsis rate = 7.0 pp, p?=?.033).

Limitations: The findings are based on data from a limited timeframe around the policy change and, thus, provide only early evidence on the effects of the new policy.

Conclusion: The new LTCH payment policy is associated with no changes in Medicare spending and mortality, but higher readmissions and post-discharge sepsis rates among severe wound patients with a high likelihood to use an LTCH.     

Exenatide BID and liraglutide QD treatment patterns among type 2 diabetes patients in Germany

Abstract

Objectives:

This study evaluated patient and prescriber characteristics, treatment patterns, average daily dose (ADD), and glycemic control of patients initiating glucagon-like peptide 1 (GLP-1) receptor agonists in Germany.

Methods:

The LifeLink? EMR-EU database was searched to identify patients initiating exenatide twice daily (BID) or liraglutide once daily (QD) during the index period (January 1, 2009–April 4, 2010). Eligible patients had ≥180 days pre-index history, ≥90 days post-index follow-up, and a pre-index type 2 diabetes diagnosis. Univariate tests were conducted at α?=?0.05.

Results:

Six hundred and ninety-two patients were included (exenatide BID 292, liraglutide QD 400): mean (SD) age 59 (10) years, 59% male. Diabetologists prescribed liraglutide QD to a larger share of patients (65% vs 35% exenatide BID) than non-diabetologists (51% vs 49%). GLP-1 receptor agonist choice was not associated with age (p?=?0.282), gender (p?=?0.960), number of pre-index glucose-lowering medications (2.0 [0.9], p?=?0.159), pre-index HbA1c (8.2 [1.5%], p?=?0.231) or Charlson Comorbidity Index score (0.45 [0.78], p?=?0.547). Mean (SD) ADD was 16.7?mcg (9.2, label range 10–20?mcg) for exenatide BID and 1.4?mg (0.7, label range 0.6–1.8?mg) for liraglutide QD. Among patients with post-index HbA1c tests, mean unadjusted values did not differ between cohorts. Exenatide BID patients were more likely than liraglutide QD patients to continue pre-index glucose-lowering medications (67.1% vs 60.3%, p?=?0.027) or to start concomitant glucose-lowering medications at index (32.2% vs 25.0%, p?=?0.013); exenatide BID patients were less likely to augment treatment with another drug post-index (15.8% vs 22.5%, p?=?0.027).

Limitations:

Results may not be generalizable. Lab measures for clinical outcomes were available only for a sub-set of patients.

Conclusions:

Results suggested that some differences exist between patients initiating exenatide BID or liraglutide QD, with respect to prescribing physician specialty and pre- and post-index treatment patterns. Both GLP-1 receptor agonists showed comparable post-index HbA1c values in a sub-set of patients.     

Predicting time to nursing home placement based on activities of daily living scores – a modelling analysis using data on Alzheimer's disease patients receiving rivastigmine or donepezil

Abstract

Objective: To quantify the impact of activities of daily living (ADL) scores on the risk of nursing home placement (NHP) in Alzheimer's disease (AD) patients.

Setting: Models predicting NHP for AD patients have depended on cognitive deterioration as the primary measure. However, there is increased recognition that both patient functioning and cognition are predictive of disease progression.

Methods: Using the database from a prospective, randomised, double-blind trial of rivastigmine and donepezil, two treatments indicated for AD, Cox regression models were constructed to predict the risk of NHP using age, gender, ADL and MMSE (Mini-Mental State Examination) scores as independent variables.

Participants: Patients aged 50–85 years, with MMSE scores of 10–20, and a diagnosis of dementia of the Alzheimer type.

Results: Cox regression analyses indicated that being female, older age, lower ADL score at baseline, and deterioration in ADL all significantly increased the risk of NHP. Over 2 years, risk of NHP increased by 3% for each 1-point deterioration in ADL score independent of cognition.

Conclusion: Data analyses from this long-term clinical trial established that daily functioning is an important predictor of time to NHP. Further research may be required to confirm whether this finding translates to the real world.