BACKGROUND:There is a need for more Comparative Effectiveness Research (CER) to strengthen the evidence base for clinical and policy decision-making. Effectiveness Guidance Documents (EGD) are targeted to clinical researchers. The aim of this EGD is to provide specific recommendations for the design of prospective acupuncture studies to support optimal use of resources for generating evidence that will inform stakeholder decision-making.METHODS:Document development based on multiple systematic consensus procedures (written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders including patients, clinicians and payers were involved.RESULTS:Recommendations focused mainly on randomized studies and were developed for the following areas: overall research strategy, treatment protocol, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication.CONCLUSION:The present EGD, based on an international consensus developed with multiple stakeholder involvement, provides the first systematic methodological guidance for future CER on acupuncture.

BACKGROUND:There is a need for more Comparative Effectiveness Research (CER) on Chinese medicine (CM) to inform clinical and policy decision-making. This document aims to provide consensus advice for the design of CER trials on CM for researchers. It broadly aims to ensure more adequate design and optimal use of resources in generating evidence for CM to inform stakeholder decision-making.METHODS:The Effectiveness Guidance Document (EGD) development was based on multiple consensus procedures (survey, written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders, including patients, clinicians, researchers and payers were involved in creating this document.RESULTS:Recommendations were developed for "using available data" and "future clinical studies". The recommendations for future trials focus on randomized trials and cover the following areas: designing CER studies, treatments, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication.CONCLUSION:The present EGD provides the first systematic methodological guidance for future CER trials on CM and can be applied to single or multi-component treatments. While CONSORT statements provide guidelines for reporting studies, EGDs provide recommendations for the design of future studies and can contribute to a more strategic use of limited research resources, as well as greater consistency in trial design.

This paper describes and tests a largely ignored but important preliminary step for comparative effectiveness research: retrospective evidence syntheses to first establish a knowledge base of condition-based medical conditions. By aggregating and organizing what is already known about a treatment or system, gaps in knowledge can be identified and future research designed to meet those gaps.An information synthesis process may also discover that few knowledge gaps in the knowledge base yet exist, the gaps are negligible, and / or treatment effectiveness and study quality is stable across many years, but is simply not clinically important. A consistent finding of low effectiveness is evidence against more research, including exclusion of a treatment from future comparative effectiveness studies. Though proponents of weak treatments or systems may choose to proceed with further research, use of public funds or resources that eventually increase costs to the public are unwarranted.By first establishing a treatment or system knowledge base, at least three comparative effectiveness research decisions are conceivable: (1) treatment or system should be included in future comparative effectiveness trials to establish relative effectiveness for a given condition, (2) has promise but requires more research in a prospective CER trial, or (3) the treatment is less effective than others for a given condition, making future research unnecessary. Thus, a "retroactive comparative effectiveness research method," rCER, is proposed here to identify which treatments are worth including in future prospective trials and which are known to have small to modest effect sizes and are not worth the time and expense of a closer look.The rCER method herein showed that for non-surgical low back pain any treatments did not improve greatly upon the normal and natural pain trajectory for acute low back pain. Therefore, any advantage in pain reduction by any treatment of acute low back pain over back pain's normal course of resolution without care, is quite small, and as such, the incremental cost for the marginal improvement over no treatment becomes quite large. While the quality of non-surgical low back pain studies over the past 34 years has steadily increased, the effect size has not, leading to the conclusion that future research on non-surgical low back pain treatment is unwarranted.

Much health related research depends heavily on the analysis of a rapidly expanding universe of observational data. A challenge in analysis of such data is the lack of sound statistical methods and tools that can address multiple facets of estimating treatment or exposure effects in observational studies with a large number of covariates. We sought to advance methods to improve analysis of large observational datasets with an end goal of understanding the effect of treatments or exposures on health. First we compared existing methods for propensity score (PS) adjustment, specifically Bayesian propensity scores. This concept had previously been introduced (McCandless et al., 2009) but no rigorous evaluation had been done to evaluate the impact of feedback when fitting the joint likelihood for both the PS and outcome models. We determined that unless specific steps were taken to mitigate the impact of feedback, it has the potential to distort estimates of the treatment effect. Next, we developed a method for accounting for uncertainty in confounding adjustment in the context of multiple exposures. Our method allows us to select confounders based on their association with the joint exposure and the outcome while also accounting for the uncertainty in the confounding adjustment. Finally, we developed two methods to combine het- erogenous sources of data for effect estimation, specifically information coming from a primary data source that provides information for treatments, outcomes, and a limited set of measured confounders on a large number of people and smaller supplementary data sources containing a much richer set of covariates. Our methods avoid the need to specify the full joint distribution of all covariates.

No description available.

Musculoskeletal complaints are one of the most common reasons for visits to medical and chiropractic professionals in the United States, and spine-related symptoms in particular comprise the largest share of these complaints. Spine-related conditions increase as people age, having implications for rising disability and consequent spending by Medicare and Medicaid on increased health services use and long-term services and support. Chiropractic is one type of treatment used by older adults with these types of health problems. Covered by Medicare since 1972, chiropractic spinal manipulation is allowed for the express purpose to arrest the progression of functional decline or restore and possibly improve patient function. No studies, however, have examined whether chiropractic use by Medicare beneficiaries has indeed arrested functional decline, delayed disability, or restored health. The purpose of this dissertation research is to examine the comparative effectiveness of chiropractic use relative to no treatment and alternative medical care on the health and functional trajectories of community-dwelling older adults. I also examine the comparative effect of chiropractic on satisfaction with care. This is accomplished through the use of two longitudinal surveys with representative Medicare populations linked to Medicare provider claims. The first analysis examines the long-term comparative effect of chiropractic relative to no use and alternative care on functional decline, self-rated health decline, and the onset of additional depressive symptoms in a cohort of older Medicare beneficiaries, both with and without back conditions. The second study examines the effect of chiropractic compared to medical only episodes of care on health and functional decline in an older adult population with uncomplicated back conditions over a two-year period. The third and final study examines the comparative effect of chiropractic relative to medical care only on one-year changes in function, self-rated health, and satisfaction with care in a nationally representative age-eligible Medicare population with spine-related musculoskeletal conditions. Study results suggest that chiropractic has a consistently protective effect when compared to routine alternative medical care against decline in function among older adults with spine-related conditions, both over the long-term and the short-term. Chiropractic also has a comparative protective effect against decline in self-rated health in the short-term, but has no differential effect on the onset of depressive symptoms either in the short-term or long-term . Medicare beneficiaries using chiropractic for spine-related health conditions are relatively more satisfied than those using medical care only with the information provided to them about their condition, and with follow-up care provided after the initial visit. This research is the first of its kind to examine the comparative effectiveness of chiropractic relative to other usual sources of care for Medicare beneficiaries, in general and specifically among those with spine-related conditions, finding that chiropractic use has a comparatively beneficial effect on function, health, and satisfaction with care. The results have important policy implications for clinicians, patients, and Medicare because of the potential to shift clinical practice away from technologically intense and expensive treatments toward therapies like chiropractic spinal manipulation that demonstrate a comparative advantage in preserving health and function among older adults.

This dissertation consists of two empirical papers and one methods paper. The first two papers use quasi-experimental methods to evaluate the impact of universal health insurance reform in Massachusetts (MA) and Thailand and the third paper evaluates the validity of a quasi-experimental method used in comparative effectiveness research (CER).

Independent and supplementary prescribing are the two main forms of non-medical prescribing (NMP) that have been practised in the UK since 2006. Most available studies have qualitatively investigated the impact of NMP, especially in primary care. This may be due to the fact that prescriptions are issued mainly by general practitioners in primary care. This PhD thesis aimed at investigating the clinical effectiveness of independent pharmacist and diabetes specialist nurse (DSN) prescribers in the management of patients with type 2 diabetes at outpatient clinics in hospitals. A literature review was firstly conducted to explore the current research on NMP around the world and the UK. A systematic review of the previously published randomised control trials (RCT) and non-RCT studies that focused on prescribing interventions of nurses and pharmacist was also conducted to explore the impact of their prescribing interventions in treating type 2 diabetes using HbA1c level as the primary outcome. A programme of work of three retrospective comparative database analytical studies was then carried out to investigate the impact of independent NMPs in type 2 diabetes care. This programme of work used electronic medical records of patients attending outpatient clinics of diabetes centres in two teaching hospitals in Manchester; one employed an independent pharmacist and the other employed DSN prescribers. A group of subjects seen by an NMP in place of a doctor during the study period were the study group and the control group were those who seen only by doctors. The primary outcome was the average yearly change of HbA1c amongst the two groups. Secondary outcomes were yearly change of total cholesterol, blood pressure and serum creatinine as well as body mass index. Five statistical models, which included multivariable regression, propensity score matching and sensitivity analyses, were utilised to control for confounding effects, and the nature of selection bias in the retrospectively comparative effectiveness research using secondary database resources. A total of 330 patients seen by a team including a pharmacist versus 975 by doctors only between January 2006 and January 2013 at one site; and 656 by a team including DSNs versus 3,746 patients seen by doctors only between January 2007 to December 2013 at the other. The studies found both prescribing pharmacists and DSNs are capable of achieving at least non-inferior improvements in diabetes outcome compared to doctors. The pharmacist achieved a mean 0.01% reduction in HbA1c level versus doctors who achieved slight increase (p<0.4). DSNs also achieved a mean 0.07% reduction compared to doctors. However, after adjustment with multivariate and propensity score as well as with propensity score matching, there were no significant differences between the two groups. These findings were consistent with the findings in the systemic review. Although an RCT is the only method that by definition would produce unbiased treatment effects, the use of propensity score methods here, have reduced the potential for bias that may remain unaccounted for in multivariate models without propensity scores. Adjusting for propensity scores using two different methods also gives more confidence that the results are as unbiased as possible. Nonetheless, caution in generalising the results is necessary because of the retrospective nature of the studies and deficiencies in the database used.

BACKGROUND:Integrative medicine (IM) is a patient-centered, healing-oriented clinical paradigm that explicitly includes all appropriate therapeutic approaches whether they originate in conventional or complementary medicine (CM). While there is some evidence for the clinical and cost-effectiveness of IM practice models, the existing evidence base for IM depends largely on studies of individual CM therapies. This may in part be due to the methodological challenges inherent in evaluating a complex intervention (i.e., many interacting components applied flexibly and with tailoring) such as IM.METHODS/DESIGN:This study will use a combination of observational quantitative and qualitative methods to rigorously measure the health and healthcare utilization outcomes of the University of Arizona Integrative Health Center (UAIHC), an IM adult primary care clinic in Phoenix, Arizona. There are four groups of study participants. The primary group consists of clinic patients for whom clinical and cost outcomes will be tracked indicating the impact of the UAIHC clinic (n=500). In addition to comparing outcomes pre/post clinic enrollment, where possible, these outcomes will be compared to those of two matched control groups, and for some self-report measures, to regional and national data. The second and third study groups consist of clinic patients (n=180) and clinic personnel (n=15-20) from whom fidelity data (i.e., data indicating the extent to which the IM practice model was implemented as planned) will be collected. These data will be analyzed to determine the exact nature of the intervention as implemented and to provide covariates to the outcomes analyses as the clinic evolves. The fourth group is made up of patients (n=8) whose path through the clinic will be studied in detail using qualitative (periodic semi-structured interviews) methods. These data will be used to develop hypotheses regarding how the clinic works.DISCUSSION:The US health care system needs new models of care that are more patient-centered and empower patients to make positive lifestyle changes. These models have the potential to reduce the burden of chronic disease, lower the cost of healthcare, and offer a sustainable financial paradigm for our nation. This protocol has been designed to test whether the UAIHC can achieve this potential.TRIAL REGISTRATION:Clinical Trials.gov NCT01785485.

Before market authorization of new medicines, their efficacy and safety are evaluated using randomized controlled trials. While there is no doubt about the scientific value of randomized trials, they are usually conducted in selected populations with questionable generalizability to routine care.  In the digital data revolution era, with healthcare data growing at an unprecedented rate, drug monitoring in routine care is still highly under-utilized. Although many countries have access to data on prescription drugs at the individual level in ambulatory care, such data are often missing for hospitals. This is a growing problem considering the clear trend towards more new and expensive drugs administered in the hospital setting. The aim of this thesis was therefore to develop methods for extracting data on drug use from a hospital-based electronic health record system and further to build and evaluate models for real-time monitoring of effectiveness and safety of new drugs in routine care using data from electronic health records and regional and national health care registers. Using the developed techniques, we were able to demonstrate drug use and health service utilization for inflammatory bowel disease and to evaluate the comparative effectiveness and safety of antiarrhythmic drugs. With a rapidly evolving drug development, it is important to optimize the evaluation of effectiveness, safety and health economic value of new medicines in routine care. We believe that the models described in this thesis could contribute to fulfil this need.