Phenome-wide association studies across large population cohorts support drug target validation.

Phenome-wide association studies (PheWAS) have been proposed as a possible aid in drug development through elucidating mechanisms of action, identifying alternative indications, or predicting adverse drug events (ADEs). Here, we select 25 single nucleotide polymorphisms (SNPs) linked through genome-wide association studies (GWAS) to 19 candidate drug targets for common disease indications. We interrogate these SNPs by PheWAS in four large cohorts with extensive health information (23andMe, UK Biobank, FINRISK, CHOP) for association with 1683 binary endpoints in up to 697,815 individuals and conduct meta-analyses for 145 mapped disease endpoints. Our analyses replicate 75% of known GWAS associations (P < 0.05) and identify nine study-wide significant novel associations (of 71 with FDR < 0.1). We describe associations that may predict ADEs, e.g., acne, high cholesterol, gout, and gallstones with rs738409 (p.I148M) in PNPLA3 and asthma with rs1990760 (p.T946A) in IFIH1. Our results demonstrate PheWAS as a powerful addition to the toolkit for drug discovery.

Innovation at the Intersection of Clinical Trials and Real-World Data Science to Advance Patient Care.

While efficacy and safety data collected from randomized clinical trials are the evidentiary standard for determining market authorization, this alone may no longer be sufficient to address the needs of key stakeholders (regulators, providers, and payers) and guarantee long-term success of pharmaceutical products. There is a heightened interest from stakeholders on understanding the use of real-world evidence (RWE) to substantiate benefit-risk assessment and support the value of a new drug. This review provides an overview of real-world data (RWD) and related advances in the regulatory framework, and discusses their impact on clinical research and development. A framework for linking drug development decisions with the value proposition of the drug, utilizing pharmacokinetic-pharmacodynamic-pharmacoeconomic models, is introduced. The summary presented here is based on the presentations and discussion at the symposium entitled Innovation at the Intersection of Clinical Trials and Real-World Data to Advance Patient Care at the American Society for Clinical Pharmacology and Therapeutics (ASCPT) 2017 Annual Meeting.

Characterizing Sleep Issues Using Twitter.

BACKGROUND: Sleep issues such as insomnia affect over 50 million Americans and can lead to serious health problems, including depression and obesity, and can increase risk of injury. Social media platforms such as Twitter offer exciting potential for their use in studying and identifying both diseases and social phenomenon. OBJECTIVE: Our aim was to determine whether social media can be used as a method to conduct research focusing on sleep issues. METHODS: Twitter posts were collected and curated to determine whether a user exhibited signs of sleep issues based on the presence of several keywords in tweets such as insomnia, "can't sleep", Ambien, and others. Users whose tweets contain any of the keywords were designated as having self-identified sleep issues (sleep group). Users who did not have self-identified sleep issues (non-sleep group) were selected from tweets that did not contain pre-defined words or phrases used as a proxy for sleep issues. RESULTS: User data such as number of tweets, friends, followers, and location were collected, as well as the time and date of tweets. Additionally, the sentiment of each tweet and average sentiment of each user were determined to investigate differences between non-sleep and sleep groups. It was found that sleep group users were significantly less active on Twitter (P=.04), had fewer friends (P<.001), and fewer followers (P<.001) compared to others, after adjusting for the length of time each user's account has been active. Sleep group users were more active during typical sleeping hours than others, which may suggest they were having difficulty sleeping. Sleep group users also had significantly lower sentiment in their tweets (P<.001), indicating a possible relationship between sleep and pyschosocial issues. CONCLUSIONS: We have demonstrated a novel method for studying sleep issues that allows for fast, cost-effective, and customizable data to be gathered.

Medicare beneficiaries' knowledge of and choices regarding Part D, 2005 to the present.

In the months before and years since Medicare Part D's implementation in January 2006, many have been concerned with beneficiaries' ability to benefit from the complex program. A systematic review of published Medline and gray literature from January 1, 2005, to August 20, 2009, was undertaken to evaluate Medicare beneficiaries' knowledge about Part D and how this knowledge informed decisions regarding enrollment and plan choice. Thirty articles that reported original results describing seniors' knowledge of the Part D benefit, decision to enroll, or selection of plans; results from patient surveys addressing these issues; or results that analyzed enrollment data or plan selection patterns were included. Of these 30 articles, 10 described beneficiaries' knowledge, 12 described enrollment and plan choices, and eight described knowledge and choice. Across studies and years, beneficiaries' knowledge of the Part D program and benefit structure and design was poor, particularly with regard to the coverage gap and the low-income subsidy. Beneficiaries had great difficulty choosing the lowest-cost Part D plans and were disinclined to switch plans to improve their benefits. Knowledge deficits, enrollment problems, and plan choice difficulties were most pronounced during Part D implementation in early 2006 but persisted in subsequent years of the benefit. Beneficiaries' knowledge and choices should be monitored on an ongoing basis to inform potential changes to the Part D program.

Specialty care systems: a pioneering vision for global health.

Successful health-sector reform in developing countries is built on sustainable service delivery models that meet reform goals while addressing community needs. When government efforts fall short, innovative private-sector solutions can offer more-efficient alternatives that provide care to impoverished populations. We identify organizations that use elements of a focused care approach to overcome barriers to delivering care in low-resource settings. Using the experience of the Aravind Eye Care System, we describe the essential elements of the specialty care model, its replication across countries, and the challenges to extending this model beyond eye care.

Self-reported utilization of health care services: improving measurement and accuracy.

Self-report is often used to estimate health care utilization. However, the accuracy of such data is of paramount concern. The authors conducted a systematic review of 42 studies that evaluated the accuracy of self-report utilization data, where utilization was defined as a visit to a clinical provider or entity. They also present a broad conceptual model that identifies major issues to consider when collecting, analyzing, and reporting such data. The results show that self-report data are of variable accuracy. Factors that affect accuracy include (1) sample population and cognitive abilities, (2) recall time frame, (3) type of utilization, (4) utilization frequency, (5) questionnaire design, (6) mode of data collection, and (7) memory aids and probes.

The cost of operating institutional review boards (IRBs).

PURPOSE: Recent reports have claimed that institutional review boards (IRBs) are underfunded, yet little is known about the costs of operating IRBs. This study estimated the costs for operating high-volume and low-volume IRBs. METHOD: IRB costs were calculated from published summary data. Costs were standardized to reflect 2001 dollars. RESULTS: Total estimated costs for operating high-volume and low-volume IRBs were $770,674 and $76,626, respectively. The average cost per action, a measure of economic efficiency, was lower for high-volume IRBs ($277 per action) than it was for low-volume IRBs ($799 per action). CONCLUSIONS: Although high-volume IRBs are more expensive than are low-volume IRBs in absolute terms, they are more economically efficient. Policy debates should consider the potential savings from large IRBs, perhaps by encouraging small IRBs to merge, although this may result in less local review, control, and oversight.

Estimating the costs of VA ambulatory care.

This article reports how we matched Common Procedure Terminology (CPT) codes with Medicare payment rates and aggregate Veterans Affairs (VA) budget data to estimate the costs of every VA ambulatory encounter. Converting CPT codes to encounter-level costs was more complex than a simple match of Medicare reimbursements to CPT codes. About 40 percent of the CPT codes used in VA, representing about 20 percent of procedures, did not have a Medicare payment rate and required other cost estimates. Reconciling aggregated estimated costs to the VA budget allocations for outpatient care produced final VA cost estimates that were lower than projected Medicare reimbursements. The methods used to estimate costs for encounters could be replicated for other settings. They are potentially useful for any system that does not generate billing data, when CPT codes are simpler to collect than billing data, or when there is a need to standardize cost estimates across data sources.

Prevalence and costs of chronic conditions in the VA health care system.

Chronic conditions are among the most common causes of death and disability in the United States. Patients with such conditions receive disproportionate amounts of health care services and therefore cost more per capita than the average patient. This study assesses the prevalence among the Department of Veterans Affairs (VA) health care users and VA expenditures (costs) of 29 common chronic conditions. The authors used regression to identify the marginal impact of these conditions on total, inpatient, outpatient, and pharmacy costs. Excluding costs of contracted medical services at non-VA facilities, total VA health care expenditures in fiscal year 1999 (FY1999) were $14.3 billion. Among the 3.4 million VA patients in FY1999, 72 percent had 1 or more of the 29 chronic conditions, and these patients accounted for 96 percent of the total costs ($13.7 billion). In addition, 35 percent (1.2 million) of VA health care users had 3 or more of the 29 chronic conditions. These individuals accounted for 73 percent of the total cost. Overall, VA health care users have more chronic diseases than the general population.