Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Regulation and function of the extracellular matrix protein tenascin-C in ovarian cancer cell lines

The extracellular matrix glycoprotein tenascin-C (TN) is overexpressed in the stroma of malignant ovarian tumours particularly at the interface between epithelia and stroma leading to suggestions that it may be involved in the process of invasion (Wilson et al (1996) Br J Cancer 74: 999-1004). To define regulation of TN further and investigate its function in ovarian cancer, a range of cell line models were studied. Concentrations of secreted TN in media from cultures of ovarian fibroblast cell lines were at least 100-fold greater than from carcinoma cell lines. Evidence for paracrine regulation of TN secretion was obtained by co-culture of carcinoma cells with fibroblast cells wherein secretion into the media was greater than from fibroblasts alone. Transforming growth factor (TGF)- beta 1, insulin-like growth factor (IGF)-II and progesterone all stimulated TN secretion while human choriogonadotropin (hCG), follicle-stimulating hormone (FSH) and gamma-interferon inhibited secretion. TGF-beta 1 produced the greatest stimulation of TN in cultured fibroblasts and its cc-expression with TN was examined in primary ovarian tumours, There was a significant association between the presence of moderate-strong expression of TN and TGF-beta 1. Evidence for TN having a functional role in ovarian carcinoma was obtained from adhesion and migration assays. The PE01, PE04, SKOV-3 and 59M cell lines all demonstrated marked adhesion to plastic coated with TN relative to the control protein bovine serum albumin (BSA) and expressed alpha 2 beta 1 and alpha 3 beta 1 integrins, The SKOV-3 cell line migrated more rapidly through TN than through BSA indicating that TN can facilitate migration of ovarian carcinoma cells

Age differences in heroin and prescription opioid abuse among enrolees into opioid treatment programs

<p>Abstract</p> <p>Background</p> <p>In the United States, among those entering opioid treatment programs (OTPs), prescription opioid (PO) abusers tend to be younger than heroin users. Admissions of older persons to OTPs have been increasing, and it is important to understand typical patterns of use among those older enrolees.</p> <p>Methods</p> <p>To disentangle the effect of age on recent heroin and PO abuse 29,114 enrolees into 85 OTPs were surveyed across 34 states from 2005-2009. OTPs where PO use was prevalent were oversampled.</p> <p>Results</p> <p>Mean age was 34; 28% used heroin only. Younger enrolees had increased odds of using POs relative to using heroin only but mixed model analysis showed that much of the total variability in type of use was attributed to variation in age between OTPs rather than within OTPs.</p> <p>Conclusions</p> <p>Organizational and cultural phenomena (e.g., OTP characteristics) must be examined to better understand the context of individual characteristics (e.g., age). If nesting of enrolees within OTPs is ignored, then associations that primarily operate at the OTP level may be misinterpreted as exclusively dependent on individuals.</p

Payer leverage and hospital compliance with a benchmark: a population-based observational study

<p>Abstract</p> <p>Background</p> <p>Since 1976, Medicare has linked reimbursement for hospitals performing organ transplants to the attainment of certain benchmarks, including transplant volume. While Medicare is a stakeholder in all transplant services, its role in renal transplantation is likely greater, given its coverage of end-stage renal disease. Thus, Medicare's transplant experience allows us to examine the role of payer leverage in motivating hospital benchmark compliance.</p> <p>Methods</p> <p>Nationally representative discharge data for kidney (<it>n </it>= 29,272), liver (<it>n </it>= 7,988), heart (<it>n </it>= 3,530), and lung (<it>n </it>= 1,880) transplants from the Nationwide Inpatient Sample (1993 – 2003) were employed. Logistic regression techniques with robust variance estimators were used to examine the relationship between hospital volume compliance and Medicare market share; generalized estimating equations were used to explore the association between patient-level operative mortality and hospital volume compliance.</p> <p>Results</p> <p>Medicare's transplant market share varied by organ [57%, 28%, 27%, and 18% for kidney, lung, heart, and liver transplants, respectively (<it>P </it>< 0.001)]. Volume-based benchmark compliance varied by transplant type [85%, 75%, 44%, and 39% for kidney, liver, heart, and lung transplants, respectively (<it>P </it>< 0.001)], despite a lower odds of operative mortality at compliant hospitals. Adjusting for organ supply, high market leverage was independently associated with compliance at hospitals transplanting kidneys (OR, 143.00; 95% CI, 18.53 – 1103.49), hearts (OR, 2.84; 95% CI, 1.51 – 5.34), and lungs (OR, 3.24; 95% CI, 1.57 – 6.67).</p> <p>Conclusion</p> <p>These data highlight the influence of payer leverage–an important contextual factor in value-based purchasing initiatives. For uncommon diagnoses, these data suggest that at least 30% of a provider's patients might need to be "at risk" for an incentive to motivate compliance.</p

Quality of life returns from basic research

<p>Abstract</p> <p>Background</p> <p>Assessing the consequences of research is an increasingly important task in research and innovation policy. This paper takes a broader view of those consequences than the conventional economic approach, placing researchers and their activities in the centre of the assessment process and examining results for professional practice and general education as well as contributions to knowledge.</p> <p>Methods</p> <p>The paper uses historical and documentary analysis to illustrate the approach, focusing on U.S. biomedicine over the past century. At aggregate level, the analysis attributes portions of the change in aggregate health indicators to research and research-based institutions, through several available types of logic: either through correlations between timing of institutional changes and changes in the indicators or through direct or indirect causal connections.</p> <p>Results</p> <p>The analysis shows that while biomedical research has certainly contributed to improved health in the United States, other factors have also contributed. In some ways the institutional structure of science-based medicine has worked against creating benefits for some groups in U.S. society.</p> <p>Conclusions</p> <p>The paper concludes with a call for more strategic attention to dimensions of impact other than knowledge outcomes and for participatory planning for research.</p

Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice

<p>Abstract</p> <p>Background</p> <p>Asthma leads to structural changes in the airways, including the modification of extracellular matrix proteins such as tenascin-C. The role of tenascin-C is unclear, but it might act as an early initiator of airway wall remodelling, as its expression is increased in the mouse and human airways during allergic inflammation. In this study, we examined whether Th1 or Th2 cells are important regulators of tenascin-C in experimental allergic asthma utilizing mice with impaired Th1 (STAT4-/-) or Th2 (STAT6-/-) immunity.</p> <p>Methods</p> <p>Balb/c wildtype (WT), STAT4-/- and STAT6-/- mice were sensitized with intraperitoneally injected ovalbumin (OVA) followed by OVA or PBS airway challenge. Airway hyperreactivity (AHR) was measured and samples were collected. Real time PCR and immunohistochemistry were used to study cytokines and differences in the expression of tenascin-C. Tenascin-C expression was measured in human fibroblasts after treatment with TNF-α and IFN-γ <it>in vitro</it>.</p> <p>Results</p> <p>OVA-challenged WT mice showed allergic inflammation and AHR in the airways along with increased expression of TNF-α, IFN-γ, IL-4 and tenascin-C in the lungs. OVA-challenged STAT4-/- mice exhibited elevated AHR and pulmonary eosinophilia. The mRNA expression of TNF-α and IFN-γ was low, but the expression of IL-4 was significantly elevated in these mice. OVA-challenged STAT6-/- mice had neither AHR nor pulmonary eosinophilia, but had increased expression of mRNA for TNF-α, IFN-γ and IL-4. The expression of tenascin-C in the lungs of OVA-challenged STAT4-/- mice was weaker than in those of OVA-challenged WT and STAT6-/- mice suggesting that TNF-α and IFN-γ may regulate tenascin-C expression <it>in vivo</it>. The stimulation of human fibroblasts with TNF-α and IFN-γ induced the expression of tenascin-C confirming our <it>in vivo </it>findings.</p> <p>Conclusions</p> <p>Expression of tenascin-C is significantly attenuated in the airways of STAT4-/- mice, which may be due to the impaired secretion of TNF-α and IFN-γ in these mice.</p

Effect of electronic patient record use on mortality in End Stage Renal Disease, a model chronic disease: retrospective analysis of 9 years of prospectively collected data

<p>Abstract</p> <p>Background</p> <p>In chronic disease, health information technology promises but has yet to demonstrate improved outcomes and decreased costs. The main aim of the study was to determine the effects on mortality and cost of an electronic patient record used in daily patient care in a model chronic disease, End Stage Renal Disease, treated by chronic maintenance hemodialysis. Dialysis treatment is highly regulated, and near uniform in treatment modalities and drugs used.</p> <p>Methods</p> <p>The particular electronic patient record, patient-centered and extensively coded, was used first in patient care in 3 dialysis units in New York, NY in 1998, 1999, and 2000. All data were stored "live"; none were archived. By December 31, 2006, the patients had been treated by maintenance hemodialysis for a total of 3924 years. A retrospective analysis was made using query tools embedded in the software. The United States Renal Data System dialysis population served as controls. In all there were 1790 patients, with many underlying primary diseases and multiple comorbid conditions affecting many organ systems. Year by year mortality, hospital admissions, and staffing were analyzed, and the data were compared with national data compiled by the United States Renal Data System.</p> <p>Results</p> <p>Analyzed by calendar year after electronic patient record implementation, mortality decreased strikingly. In years 3–9 mortality was lower than in years 1–2 by 23%, 48%, and 34% in the 3 units, and was 37%, 37%, and 35% less than that reported by the United States Renal Data System. Clinical staffing was 25% fewer per 100 patients than the national average, thereby lowering costs.</p> <p>Conclusion</p> <p>To our knowledge, this is the first demonstration that an electronic patient record, albeit of particular design, can have a favorable effect on outcomes and cost in chronic disease. That the population studied has many underlying diseases affecting all organ systems suggests that the electronic patient record design may enable application to many fields of medical practice.</p

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

No short-cut in assessing trial quality: a case study

Assessing the quality of included trials is a central part of a systematic review. Many check-list type of instruments for doing this exist. Using a trial of antibiotic treatment for acute otitis media, Burke et al., BMJ, 1991, as the case study, this paper illustrates some limitations of the check-list approach to trial quality assessment. The general verdict from the check list type evaluations in nine relevant systematic reviews was that Burke et al. (1991) is a good quality trial. All relevant meta-analyses extensively used its data to formulate therapeutic evidence. My comprehensive evaluation, on the other hand, brought to the surface a series of serious problems in the design, conduct, analysis and report of this trial that were missed by the earlier evaluations. A check-list or instrument based approach, if used as a short-cut, may at times rate deeply flawed trials as good quality trials. Check lists are crucial but they need to be augmented with an in-depth review, and where possible, a scrutiny of the protocol, trial records, and original data. The extent and severity of the problems I uncovered for this particular trial warrant an independent audit before it is included in a systematic review

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy

The tissue distribution of anti-tumour vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, the source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of 125I-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in vivo. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer. © 1999 Cancer Research Campaig