Early symptoms of cognitive impairment are frequently undetected. The Davos Alzheimer’s Collaborative System Preparedness (DAC-SP) Early Detection program implemented a digital cognitive assessment (DCA) in primary care and other non-specialty settings to increase the rate of detection of cognitive impairment. The DAC-SP Early Detection program was initiated in 2021 in seven healthcare systems across six countries. Clinicians were trained on a DCA, including positive tests for cognitive impairment and diagnostic assessment. Prior to training or naïve to implementing a DCA in clinical practice, clinicians’ attitudes and confidence in diagnosis and managing dementia were assessed using the validated General Practitioners Attitude and Confidence Scale for Dementia (GPACS-D), which is comprised of 15 items in three subscales: Confidence in Clinical Abilities, Attitude towards Care, and Engagement. Each item is measured on a 5-point Likert scale (1 = strongly disagree; 5 = strongly agree), and subscale scores are standardized. A total of 265 pre-training surveys were completed across the 7 sites. The GPACS-D results were calculated by averaging individual physician results per the validated scoring algorithm. The cross-site results were calculated by taking an equally weighted average across the seven sites. The GPACS-D results across the seven sites are presented in Table 1. Across all sites, baseline attitude towards care was the highest of the three subscales. For most sites, confidence in clinical abilities received the lowest scores, with engagement scores only modestly higher. The total and subscale scores were consistent across sites, supported by the relatively low standard deviation. The findings from the GPACS-D total and subscale scores suggest that prior to receiving training on using a digital cognitive assessment for their patient populations, clinicians’ attitudes towards the diagnosis and management of cognitive impairment were similar across the seven sites, and independent of the country in which they practice. Despite positive attitudes toward care, the results suggest that education or training focused more on engagement and confidence may improve early detection and care of patients with cognitive impairment, particularly as new diagnostic and therapeutic options emerge.

Background The number of people with dementia is expected to grow substantially across the world due to population aging, but cognitive impairment remains undetected and undiagnosed, especially in early stages. Newly available diagnostic tools such as digital cognitive assessments and blood biomarker tests may be well suited to increase the rates of early detection of dementia in primary care. Objectives The objective of the Davos Alzheimer's Collaborative Healthcare System Preparedness (DAC-SP) Early Detection Flagship Program was to improve the rate of early detection of cognitive impairment in primary care and non-specialty settings. We aimed to understand the program's impact on clinician attitudes, engagement, and confidence in diagnosing and managing cognitive impairment. Design Survey of participating healthcare professionals before and after the intervention. Setting The DAC Healthcare System Preparedness Early Detection Flagship Program was implemented in seven sites across six countries: Brazil, Jamaica, Japan, Mexico, Scotland, and the United States (2 sites). Participants 110 healthcare professionals, including, primary care physicians, specialists (neurologists and psychologists), nurses, nurse practitioners, physician assistants, social workers, and healthcare support workers completed the pre-intervention survey. 68 healthcare professionals completed the post-intervention survey. Intervention Participating sites implemented a digital cognitive assessment tool and a blood biomarker test for the Alzheimer's pathology and were trained in the administration of the digital cognitive assessment tool. The intervention was adapted to each site for cultural relevance and operational feasibility. Measurements Participants completed the General Practitioners Attitude and Confidence Scale for Dementia (GPACS-D), a 15-item scale with three subscales: Attitude to Care (six items), Confidence in Clinical Abilities (six items), and Engagement (three items). In addition to the subscale scores, the total GPACS-D score was reported. Results Across all sites, there was a significant increase in the Confidence in Clinical Abilities score from 2.98 (SD = 0.77) pre-intervention to 3.27 (SD = 0.72) post-intervention (p = 0.01), and in the total GPACS-D score from 3.48 (SD = 0.48) to 3.65 (SD = 0.39) (p = 0.01). There were non-significant increases in the Attitude to Care and Engagement scores across all sites. Conclusions The implementation of digital cognitive assessment tools and a blood biomarker test was associated with an increase in healthcare professionals’ confidence in diagnosing and managing patients with cognitive impairment in primary care and non-specialty settings. Digital cognitive assessments and blood biomarker tests are promising tools that could be utilized in primary care to increase clinicians’ confidence in detecting dementia and lead to timely clinical evaluation, treatment, and referral to supportive resources.

Blood-based biomarker tests are critical tools with the potential to change pathways for dementia diagnosis and care. These tests are less invasive than PET scan or lumbar puncture, potentially more affordable, and thus more accessible across more care settings and in more countries. Utilization in primary care settings together with brief cognitive assessments provides a compelling use case that could transform diagnosis, assessment and care. A critical challenge to the widespread adoption of blood-based biomarker testing is the issue of disclosure. To date, Alzheimer’s Disease and Related Dementias (ADRD) biomarker disclosure recommendations have primarily focused on disclosure in research and/or specialized-care settings. Primary care clinicians are well situated to conduct biomarker testing, but they are likely to need training and support to develop confidence and capacity to communicate results. Review of literature findings involving biomarker disclosure and input from dementia researchers from six countries reflecting diverse health care systems informed development of a disclosure framework to support the inaugural project of the Davos Alzheimer’s Collaborative’s (DAC) Systems Preparedness (DAC-SP) initiative. This project seeks to promote routine uptake of cognitive screening among people ≥ age 60 and, when cognitive impairment is identified, blood-based biomarker testing. The biomarker testing is completed using a commercially available, CLIA-certified test that measures the likelihood of amyloid pathology when cognitive impairment is identified. The framework recognizes that biomarker disclosure is part of a comprehensive patient evaluation that includes cognitive assessment and a broader discussion of the patient’s health and wellbeing. It divides disclosure into five phases: pre-test education; consent for and administration of testing; disclosure of results and discussion of treatment plan; provision of educational materials; and follow up (Table 1). This general framework can be adapted for site-specific factors such as health literacy, health systems operations, legal structures, and cultural relevance. As part of a pragmatic multisite implementation evaluation of a screening and early detection program including high and middle income countries, the authors have developed a framework to guide biomarker disclosure to patients in primary care settings. This provisional framework represents an important first step towards clinical consensus building on biomarker disclosure.

Confronting Alzheimer's disease (AD) involves patients, healthcare professionals, supportive services, caregivers, and government agencies interacting along a continuum from initial awareness to diagnosis, treatment, support, and care. This complex scope presents a challenge for health system transformation supporting individuals at risk for, or diagnosed with, AD. The AD systems preparedness framework was developed to help health systems identify specific opportunities to implement and evaluate focused improvement programs. The framework is purposely flexible to permit local adaptation across different health systems and countries. Health systems can develop solutions tailored to system-specific priorities considered within the context of the overall framework. Example metric concepts and initiatives are provided for each of ten areas of focus. Examples of funded projects focusing on screening and early detection are provided. It is our hope that stakeholders utilize the common framework to generate and share additional implementation evidence to benefit individuals with AD.

INTRODUCTION:This study estimated the minimal clinically important difference (MCID) for Mini Mental State Examination, Clinical Dementia Rating Scale sum of boxes, and Functional Activities Questionnaire across the Alzheimer's disease (AD) spectrum.METHODS:Retrospective analysis of the National Alzheimer's Coordinating Center Uniform Data Set (9/2005-9/2016) and MCID for clinical outcomes were estimated using anchor-based (clinician's assessment of meaningful decline) and distribution-based (1/2 baseline standard deviation) approaches, stratified by severity of cognitive impairment.RESULTS:On average, a 1-3 point decrease in Mini Mental State Examination, 1-2 point increase in Clinical Dementia Scale sum of boxes, and 3-5 point increase in Functional Activities Questionnaire were indicative of a meaningful decline. The MCID values generally increased by disease severity; the effect size and standardized response mean for those with meaningful decline were consistently in the acceptable ranges for MCID.DISCUSSION:These findings can inform design and interpretation of future clinical trials.

BACKGROUND:Effectiveness of Alzheimer's disease (AD) treatments may depend critically on the timeliness of intervention.OBJECTIVE:To compare characteristics and outcomes of patients diagnosed with probable AD (prAD) based on time elapsed from first onset of cognitive decline.METHODS:Patients with ≥1 prAD diagnosis and ≥1 follow-up visit were selected from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS; 9/2005-6/2015) and stratified based on the time between the perceived onset of cognitive decline at baseline and first prAD diagnosis (i.e., earlier versus later diagnosis). Characteristics at baseline and prAD diagnosis, clinically meaningful progression, and medication use following prAD diagnosis were compared.RESULTS:Median time from perceived onset of cognitive decline to prAD diagnosis was 4.5 years (earlier diagnosis: ≤3.46; later diagnosis: >5.71). Earlier-diagnosed patients (n = 1,476) were younger at baseline (74.3 versus 76.3 years) and had better cognitive and functional scores than later-diagnosed patients (n = 1,474). At first prAD diagnosis, earlier-diagnosed patients had lower mean global Clinical Dementia Rating (CDR) score (0.8 versus 1.1), higher mean Mini-Mental State Examination (MMSE) (22.6 versus 20.0), and lower mean Functional Activities Questionnaire (11.6 versus 17.3). Earlier- and later-diagnosed patients experienced similar time to a decrease of ≥3 points in MMSE (median 23.2 versus 23.1 months, p = 0.83), but earlier-diagnosed patients had longer time to a CDR score of ≥2 points, and longer times to initiation of AD medication and antipsychotic agents (all p < 0.01).CONCLUSION:Earlier prAD diagnosis in NACC data is associated with higher cognitive function and lower functional impairment at diagnosis.

The objective of this study was to examine patient characteristics and health care resource utilization (HCRU) in the 36 months prior to a confirmatory diagnosis of Alzheimer’s disease (AD) compared to a matched cohort without dementia during the same time interval.

Empirical evidence regarding minimal clinically important difference (MCID) estimates for clinical outcome assessments across the Alzheimer's disease (AD) spectrum is limited. Using anchor-based and distribution-based approaches, this study estimated the MCID for the Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR) Scale - global and sum of boxes (SB) scores, and the Functional Assessment Questionnaire (FAQ) for patients stratified by cognitive impairment stage. Patients with ≥2 visits to Alzheimer's Disease Centers (ADCs) were identified from the National Alzheimer's Coordinating Center Uniform Data Set (9/2005-9/2016), and stratified into the following cohorts (Table 1): 1) Normal cognition, 2) Mild cognitive impairment (MCI)-AD, 3) Mild AD dementia, 4) Moderate-severe AD dementia. For each cohort, mean changes from previous visit, effect size (ES), standardized response mean (SRM), and half of the standard deviation at baseline (½ SD) for MMSE, CDR, and FAQ scores were estimated and stratified by whether, in the clinician's assessment, there was a meaningful decline in cognitive, behavioral, or functional attributes from the previous visit. Analyses were performed at a visit level. Using a clinician's assessment of meaningful decline since the previous visit as an anchor, on average, a 2-3 point decrease in MMSE, 0.2-0.3 point increase in global CDR, 1-2 point increase in CDR-SB, and 3-5 point increase in FAQ were indicative of a meaningful decline (Table 2; overall). The proportion of visits with meaningful decline increased with more advanced stages of cognitive impairment (Table 2). The MCID values also generally increased by stage, and the observed ES/SRM for those with meaningful decline were consistently in the acceptable ranges for MCID (ES: 0.2-0.5; SRM: 0.4-0.8), whereas the ES/SRM among visits with no meaningful decline were very small. Results from the distribution-based method (½ SD) supported the anchor-based approach. These findings provide estimates of MCID based on clinical practice in ADCs which may be used to inform the design and interpretation of future trials. Application of these MCID estimates as responder definitions in contemporary clinical trials warrants further exploration. The findings also suggest that it is important to account for variation in MCID by disease severity.

Alzheimer's disease (AD) is associated with a gradual decline, making it difficult to identify distinct clinical milestones of progression. Previous work describes the utility of functional dependence; the level of assistance a patient requires consequent to AD deficits, as meaningful interim milestones of clinical progression. This study characterizes patterns in change of dependence over 36 months in community dwelling AD participants in the GERAS prospective, naturalistic, observational study. GERAS participants from France and Germany had the opportunity for 36-month followup and comprise the analytic cohort. Individuals aged ≥55 years, diagnosed with probable AD [Mini-Mental State Examination (MMSE) score ≤26]) with a caregiver were eligible. AD participants were stratified according to disease severity by baseline MMSE scores and assigned to one of six derived dependence levels, based on AD Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) response patterns (Table 1). Dependence levels were characterized at baseline, 18, and 36 months for those with available data and the full population with missing values imputed by last observation carried forward (LOCF). Data was available for 969 patients (France = 419; Germany = 550) at baseline, while 668 and 404 patients had data at 18 and 36-months respectively. Greater dependence was observed at baseline for more advanced stages of disease (Fig 1). Figure 2 characterizes dependence level changes among baseline mild AD participants. At 18 months, 47.1% had no change, while 25.4%, 13.2% and 3.6% worsened by 1, 2 or ≥3 levels respectively. Comparable 36-month figures were 42.2% without change while 23.5%, 20.1% and 10.8% worsened by 1, 2 or ≥3 levels, respectively. A similar general pattern in dependence was seen for the LOCF cohort, however with more advanced progression noted. Distribution of dependence levels according to baseline AD severity at (a) baseline. Distribution of dependence levels according to baseline AD severity at (b) 18 months. Distribution of dependence levels according to baseline AD severity at (c) 36 months. Change in dependence levels for baseline mild AD patients between baseline visit and (a) 18 months. Change in dependence levels for baseline mild AD patients between baseline visit and (b) 36 months. Considerable progression on dependence, reflecting greater equivalent care needs, was observed over 36 months. Transforming continuous functional scale scores into discrete levels of dependence provides an outcome approach that captures meaningful interim clinical milestones. Future research should confirm the suitability of dependence levels as an outcome to assess treatment benefits in AD clinical trials.

BACKGROUND:Spouses of Alzheimer's disease patients (AD spouses) may experience substantial health effects associated with their partner's chronic cognitive and behavioral dysfunction. Studies examining associations between the medical experiences of AD spouses in the period before and after their partner's AD diagnosis are limited, particularly those which measure health care resource use and cost.METHODS:AD patients were identified through multiple Medicare claims containing an AD diagnostic code. Their spouses were identified through special coding in the Medicare eligibility records. The AD spouses were matched demographically to the spouses of Medicare beneficiaries without a history of AD. Longitudinal and annual cross-sectional Medicare cost comparisons utilized log-transformed linear regression. The longitudinal period of observation began 12 months before the AD patient's initial claim listing AD and continued for up to 38 months afterwards.RESULTS:The study identified 16,322 AD spouses. Total per person costs were 24% higher in AD spouses than in the controls ($694/month vs $561/month). AD spouses' excess costs began 3 months before their partners' AD diagnoses and continued for ≥30 months. Being an AD spouse predicted 29% higher Medicare costs after adjustment for chronic health status (P < .001). Increasing AD patient care complexity had a substantial impact on AD spouse Medicare costs (P < .001).CONCLUSIONS:This study documents a link between the health status of AD spouses and AD patients. Additional research is required to elicit the mechanism behind the association between AD spouse and AD patient diagnosis.

AIM:To assess the cost-effectiveness of first-line pemetrexed/platinum and other commonly administered regimens in a representative US elderly population with advanced non-squamous non-small cell lung cancer (NSCLC).MATERIALS AND METHODS:This study utilized the Surveillance Epidemiology and End Results (SEER) cancer registry linked to Medicare claims records. The study population included all SEER-Medicare patients diagnosed in 2008-2009 with advanced non-squamous NSCLC (stages IIIB-IV) as their only primary cancer and who started chemotherapy within 90 days of diagnosis. The study evaluated the four most commonly observed first-line regimens: paclitaxel/carboplatin, platinum monotherapy, pemetrexed/platinum, and paclitaxel/carboplatin/bevacizumab. Overall survival and total healthcare cost comparisons as well as incremental cost-effectiveness ratios (ICERs) were calculated for pemetrexed/platinum vs each of the other three. Unstratified analyses and analyses stratified by initial disease stage were conducted.RESULTS:The final study population consisted of 2,461 patients. Greater administrative censorship of pemetrexed recipients at the end of the study period disproportionately reduced the observed mean survival for pemetrexed/platinum recipients. The disease stage-stratified ICER analysis found that the pemetrexed/platinum incurred total Medicare costs of $536,424 and $283,560 per observed additional year of life relative to platinum monotherapy and paclitaxel/carboplatin, respectively. The pemetrexed/platinum vs triplet comparator analysis indicated that pemetrexed/platinum was associated with considerably lower total Medicare costs, with no appreciable survival difference.LIMITATIONS:Limitations included differential censorship of the study regimen recipients and differential administration of radiotherapy.CONCLUSIONS:Pemetrexed/platinum yielded either improved survival at increased cost or similar survival at reduced cost relative to comparator regimens in the treatment of advanced non-squamous NSCLC. Limitations in the study methodology suggest that the observed pemetrexed survival benefit was likely conservative.

Due to the growing global health impact of Alzheimer's disease (AD), there is a greater need for interventions that prevent or delay the onset of clinical symptoms of this debilitating disease. Clinical trials for disease-modifying compounds in AD have shifted towards earlier stages in the spectrum of illness, including the stage prior to cognitive symptoms. A population of specific interest for clinical research includes individuals with evidence of Alzheimer's disease pathology who are asymptomatic (ADPa). The challenges and barriers regarding medical treatment of ADPa must be identified and addressed prior to the completion of a positive clinical trial in order to accelerate the translation of research findings to clinical practice. This report applies an existing public health impact model from Spencer and colleagues (2013) to evaluate the readiness of the clinical practice environment to treat ADPa individuals if a disease-modifying agent achieves approval. We contrast the current clinical practice environment with a potential future state through investigating the effectiveness, reach, feasibility, sustainability, and transferability of the practice of treating ADPa individuals.

Significant proportions of people with Alzheimer’s disease (AD) go undiagnosed or receive a delayed diagnosis. The effectiveness of treatments for AD may depend critically on the timeliness of intervention. This study compares demographic and clinical characteristics, as well as downstream outcomes, of patients diagnosed with probable AD (prAD) based on time elapsed from first onset of cognitive decline (CD). Patients with 1 clinical diagnosis of prAD between 2005-2015 and 1 follow-up visit after diagnosis were selected from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set and stratified based on time between onset of CD reported at intake and first prAD diagnosis. Patients in the bottom (i.e., shorter) tertile of time to prAD diagnosis were classified as ‘earlier’ and those in the top tertile as ‘later’. The cohorts were compared in terms of characteristics at intake and at diagnosis of prAD, as well as clinically meaningful progression and medication use over time following prAD diagnosis. 4,428 prAD patients were identified (mean age: 75; 46% male). Median time from onset of CD to prAD diagnosis was 4.5 years, with earlier diagnosis defined as ≤3.46 years and later as >5.71 years. Patients diagnosed earlier (N=1,476) were younger at intake (74.3 vs. 76.3; p<0.01) and had better cognitive and functional scores. At first diagnosis of prAD, earlier-diagnosed patients had a lower mean global Clinical Dementia Rating score (0.8 vs. 1.1), higher mean Mini Mental State Examination (MMSE) (22.6 vs. 20.0), and lower mean Functional Activities Questionnaire (11.6 vs. 17.3) and were more likely to live independently (29.4% vs. 14.1%); all p<0.01. Earlier- and later-diagnosed patients experienced similar time to decrease of 3 points in MMSE (median 23.2 vs. 23.1 months, p=0.83), but earlier-diagnosed patients had longer times to initiation of AD medication and antipsychotic agents (both p<0.01). Earlier diagnosis of prAD in NACC data is associated with higher cognitive function, greater independence, and lower functional impairment at diagnosis. The findings suggest that as future therapies become available, earlier-diagnosed patients could be treated while cognitive and functional abilities are greater, potentially increasing patient benefit.

It is not known if there is a differential impact on Alzheimer’s disease (AD) diagnosis and outcomes if/when patients are diagnosed with cognitive decline by specialists versus non-specialists. This study examined the cost trajectories of Medicare beneficiaries initially diagnosed by specialists compared to similar patients who received their diagnosis in primary care settings.

Purpose: In Europe, pancreatic cancer (PC) accounts for approximately 2.6% of all new cancer cases and is the fourth leading cause of cancer-related death. Despite substantial morbidity and mortality, limited data are available describing real-world treatment patterns and health care resource use in any European country. We evaluated PC-related treatment patterns and associated health care resource use among patients with metastatic PC in the United Kingdom and France.Methods: One hundred three oncology specialists (53 in France and 50 in the United Kingdom) abstracted data from medical records of 400 patients whom they treated for metastatic PC. Eligible patients had a diagnosis of metastatic PC at age 18 years or older between January 1, 2009, and December 31, 2012; had >= 3 months of follow-up time beginning at metastatic diagnosis; and received at least 1 cancer-directed therapy for metastatic disease. Information on patient demographics, Eastern Cooperative Oncology Group performance status, location of primary tumor, presence of comorbidities, adverse events, and complications were collected. Data on cancer-directed treatments and supportive care measures were evaluated. All analyses were descriptive.Findings: Approximately two thirds of patients were men, and median age at metastatic disease diagnosis was 62.2 years. Nearly all patients (97.3%) received chemotherapy to treat metastatic disease, 9.3% received radiation therapy, and 7.8% received a targeted therapy. Overall, the most frequently administered first-line regimens for metastatic disease were gemcitabine alone (46.0%), a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX; 20.1%); gemcitabine/capecitabine (10.8%); and gemcitabine/oxaliplatin (9.5%). Approximately 40% of patients in France and 15% of patients in the United Kingdom received second-line systemic therapy, whereas 20% of patients in France and 3.4% of patients in the United Kingdom received third-line systemic therapy for metastatic disease. Overall, 52.5% of patients experienced at least one complication of PC. More than two thirds of patients had >= 1 office visit unrelated to chemotherapy administration, 54.0% had >= 1 inpatient hospitalization, 36.8% had >= 1 emergency department visit, and 25.3% had >= 1 pain management clinic visit. A total of 26.5% of patients in France and 42.5% in the United Kingdom entered hospice or long-term care.Implications: This study provides new, detailed information for patients with metastatic PC in real-world settings in 2 European countries. A small proportion of patients received > 1 line of systemic therapy for metastatic disease, which is likely due tothe aggressiveness of this disease and the lack of effective therapeutic options. (C) 2015 The Authors. Published by Elsevier HS Journals, Inc.

Abstract Objective: A potential complication for all new multiple myeloma (MM) patients is the clinical presentation of osteolytic lesions which increase the risk for skeletal-related events (SREs). However, the contribution of SREs to the overall economic impact of MM is unclear. The impact of SREs on healthcare resource utilization (HCRU) and costs for US patients with MM was analyzed in Truven Health Marketscan Commercial Claims and Medicare Supplemental Databases. Methods: Adults diagnosed with MM between January 1, 2005 and December 31, 2010 with ≥2 claims ≥30 days apart (first claim = index date) were included. SREs included: hypercalcemia, pathologic fracture, surgery for the prevention and treatment of pathologic fractures or spinal cord compression, and radiation for bone pain. Rates of HCRU (outpatient [OP], inpatient [IP], emergency room [ER], orthopedic consultation [OC], and ancillary) and healthcare costs were compared between MM patients with and without SREs. Inverse propensity weighting was applied to adjust for potential bias. Results: Of 1028 MM patients (mean age = 67, standard deviation = 13.2), 596 patients with ≥1 SRE and 432 without SREs were assessed. HCRU rates in IP, ER, and ancillary (p < 0.01) and mean total costs of OP, IP, and ER were significantly higher (p < 0.05) for patients with vs without SREs during follow-up. HCRU rates also increased with SRE frequency (p < 0.05 in OP, IP, ER, OC, and ancillary), as did mean total healthcare costs, except for OC (p < 0.001). Limitations: A broad assessment of pharmacotherapy for the treatment of MM was not an objective of the current study. Bisphosphonate use was evaluated; however, results were descriptively focused on frequency of utilization only and were not included in the broader cost and HCRU analysis. Conclusions: Among US patients with MM, higher SRE frequency was associated with a significant trend of higher HCRU and total healthcare costs in several settings.

PURPOSE:To evaluate the advantages and disadvantages of pre-approval requirements for safety data to detect cardiovascular (CV) risk contained in the December 2008 U.S. Food and Drug Administration (FDA) guidance for developing type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the perspective of diabetes population health. METHODS:We applied the incremental net health benefit (INHB) framework to quantify the benefits and risks of investigational diabetes drugs using a common survival metric (life-years [LYs]). We constructed a decision analytic model for clinical program development consistent with the requirements of each guidance and simulated diabetes drugs, some of which had elevated CV risk. Assuming constant research budgets, we estimate the impact of increased trial size on drugs investigated. We aggregate treatment benefit and CV risks for each approved drug over a 35-year horizon under each guidance. RESULTS:The quantitative analysis suggests that the December 2008 guidance adversely impacts diabetes population health. INHB was -1.80 million LYs, attributable to delayed access to diabetes therapies (-0 .18 million LYs) and fewer drugs (-1.64 million LYs), but partially offset by reduced CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses. CONCLUSION:The health outcomes impact of all potential benefits and risks should be evaluated in a common survival measure, including health gain from avoided adverse events, lost health benefits from delayed or for gone efficacious products, and impact of alternative policy approaches. Quantitative analysis of the December 2008 FDA guidance for diabetes therapies indicates that negative impact on patient health will result.

BACKGROUND:The burden experienced by spouses of patients with Alzheimer's disease (AD) may have negative consequences for their physical health. We describe here a method for analyzing United States Medicare records to determine the changes in health service use and costs experienced by spouses after their marital partner receives an AD diagnosis.METHODS:We initially identified all beneficiaries in the 2001-2005 Medicare 5% sample who had multiple claims listing the ICD-9 diagnostic code for AD, 331.0. The 5% sample includes spouses who share a Medicare account with their marital partners because they lack a sufficient work history for full eligibility on their own. A matched cohort study assessed incremental health costs in the spouses of AD patients versus a control group of spouses of non-AD patients. Longitudinal and cross-sectional analyses tracked the impact of a patient's AD diagnosis on his or her spouse's healthcare costs.RESULTS:Our method located 54,593 AD patients of whom 11.5% had spouses identifiable via a shared Medicare account. AD diagnosis in one member of a couple was associated with significantly higher monthly Medicare payments for the other member's healthcare. The spouses' elevated costs commenced 2 to 3 months before their partners' AD diagnosis and persisted over the follow-up period. After 31 months, the cumulative additional Medicare reimbursements totaled a mean $4,600 in the spouses of AD patients. This excess was significant even after accounting for differences in baseline health status between the cohorts.CONCLUSION:The study methodology provides a framework for comprehensively evaluating medical costs of both chronically ill patients and their spouses. This method also provides monthly data, which makes possible a longitudinal evaluation of the cost effects of specific health events. The observed correlations provide a coherent demonstration of the interdependence between AD patients' and spouses' health. Future research should examine caregiving burden and other possible factors contributing to the AD spouses' health outcomes. It should also extend the method presented here to evaluations of other chronic diseases of the elderly.

This study looked at the impact of Medicare Part D coverage gaps by examining drug discontinuation and reinitiation among Medicare beneficiaries using medications for cancer or rheumatoid arthritis. The study found that patients in the arthritis or cancer groups—28 and 21 percent, respectively—discontinued medications for these conditions in 2006; about three-fourths reinitiated therapy in the first 90 days of 2007. Although medication discontinuation is often temporary, the effect is complex. Some patients might discontinue before reaching the coverage gap to avoid out-of-pocket costs. For those who spend into or through the coverage gap before discontinuing, cumulative out-of-pocket expenditures might be too high to resume treatment the following year.