Evidence Inference 2.0: More Data, Better Models

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.Comment: Accepted as workshop paper into BioNLP Updated results from SciBERT to Biomed RoBERT

Advanced Designs of Cancer Phase I and Phase II Clinical Trials

The clinical trial is the most import study for the development of successful novel drugs. The aim of this dissertation is to develop innovative statistical methods to overcome the three main obstacles in clinical trials: (1) lengthy trial duration and inaccurate maximum tolerated dose (MTD) in phase I trials; (2) heterogeneity in drug effect when patients are given the same prescription and same dose; and (3) high failure rates of expensive phase III confirmatory trials due to the discrepancy in the endpoints adopted in phase II and III trials. Towards overcoming the first obstacle, we originally develop a hybrid design for the time-to-event dose escalation method with overdose control using a normalized equivalent toxicity score (NETS) system. This hybrid design can substantially reduce sample size, shorten study length, and estimate accurate MTD by employing a parametric model and adaptive Bayesian approach. Toward overcoming the second obstacle, we propose a new approach to incorporate patients’ characteristic using our proposed design in phase I clinical trials which considers the personalized information for patients who participant in the trials. To conquer the third obstacle, we propose a novel two-stage screening design for phase II trials whereby the endpoint of percent change in of tumor size is used in an initial screening to select potentially effective agents within a short time interval followed by a second screening stage where progression free survival is estimated to confirm the efficacy of agents. These research projects will substantially benefit both cancer patients and researchers by improving clinical trial efficiency and reducing cost and trial duration. Moreover, they are of great practical meaning since cancer medicine development is of paramount importance to human health care

The Disfranchisement of Fertile Women in Clinical Trials: The Legal Ramifications of and Solutions for Rectifying the Knowledge Gap

Twice as many women as men receive treatment for clinical depression, yet men benefit more than women from antidepressant drug treatment. Likewise, women use more prescription drugs than men, but suffer proportionally more side effects.\u27 Such disparities stem from the traditional attitude of pharmaceutical companies and researchers to- ward the use of women in clinical trials. In general, researchers have tested drugs on young white males without regard for gender differences, often assuming that data extrapolated from studies on males are readily applicable to females. Even medical treatments designed exclusively for women are developed and tested based on a male model, regardless of the fact that women often react differently to many treatments than men do. Researchers generalize information received from male-oriented studies without sufficient information to show that such treatments will be effective or safe for use by women. The net result has been the marketing of drugs that are less effective for, and often dangerous to, women. Researchers and pharmaceutical companies historically have given many reasons for their decision to use a male model in drug development and testing. Increasingly, however, the medical community, women\u27s health organizations, Congress, and some administrative agencies believe that the exclusion of women from clinical trials is a grave oversight with potentially devastating consequences.\u27 Recently, government agencies and private organizations have taken steps toward encouraging pharmaceutical companies and researchers to include women in clinical trials, but these efforts have had only moderate success

The Role of Racial Identity and Religious Beliefs in the Attitudes of African American Cancer Patients Toward and Intention To Enroll in Therapeutic Cancer Trials

There is increasing evidence that societal inequities and cultural differences in attitudes toward cancer and its treatment drive health outcomes. Therapeutic clinical trials represent a promising treatment option for cancer patients, yet the percentage of African American patients who enroll in clinical trials is lower than the national average. This creates a racial imbalance that limits the extent to which research results from clinical trials can be generalized. Studies of African Americans report some attitudes toward trial participation are based on trust and fear. Enrollment of minority patients is necessary to collect group specific data, and adapt treatments as may be necessary. To that end, interventions aimed at shifting attitudes hol promise, but hinge upon a better understanding of the interplay between attitudes toward trial participation, cultural constructs, and enrollment. The purpose of this dissertation was to examine interrelationships between two socio-cultural constructs, and four attitudinal barriers to clinical trial participation among African American cancer patients. Specifically, the study sought to (1) understand the relationship between attitudinal barriers to clinical trial participation and the subsequent intention to enroll; (2) understand the contribution of racial identity (racial centrality) and religious belief (specifically a belief in `God as healer') to intention to enroll. The study was guided by elements of the Theory of Planned Behavior and theories of racial identity and religiosity. Interviews were conducted with 111 African American cancer patients in a purposive sample from an urban, community-based teaching hospital in Washington, D.C. Logistic regression analyses explored the predictive value of four attitudinal constructs in patients' intention to enroll. Three of the four attitudinal barriers were significant predictors of intention for this sample. The concern about ethical conduct of investigators was the only attitudinal barrier that remained statistically significant in the unadjusted model (OR =0.85, p=0.04). Racial identity and a belief in God as healer were not significant predictors of intention to enroll. Finally, a moderation analysis explored the effect of levels of racial centrality and religious belief on attitudes and on intention. A belief in God as healer significantly moderated the association between the concern about ethical conduct of investigators and intention to enroll in a therapeutic clinical trial. Among participants with a low belief in God as a healer, a lower level of concern about the ethical conduct of investigators predicted a greater intention to enroll than those with a higher level of concern about ethics. Racial centrality did not significantly moderate any of the attitudinal barriers. The extant literature is scant in terms of addressing the role that socio-cultural constructs play in clinical trial decision-making for African American patients. In particular, implications of this study suggest that the historical legacy of research abuse and unethical treatment of African Americans in research continues to color attitudes towards clinical trials. This study provides a basis for further exploration of socio-cultural moderators among African Americans, an understanding of which may enable tailoring of interventions on these factors, which may improve intervention effects

KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission

Renewed global efforts toward malaria eradication have highlighted the need for novel antimalarial agents with activity against multiple stages of the parasite life cycle. We have previously reported the discovery of a novel class of antimalarial compounds in the imidazolopiperazine series that have activity in the prevention and treatment of blood stage infection in a mouse model of malaria. Consistent with the previously reported activity profile of this series, the clinical candidate KAF156 shows blood schizonticidal activity with 50% inhibitory concentrations of 6 to 17.4 nM against P. falciparum drug-sensitive and drug-resistant strains, as well as potent therapeutic activity in a mouse models of malaria with 50, 90, and 99% effective doses of 0.6, 0.9, and 1.4 mg/kg, respectively. When administered prophylactically in a sporozoite challenge mouse model, KAF156 is completely protective as a single oral dose of 10 mg/kg. Finally, KAF156 displays potent Plasmodium transmission blocking activities both in vitro and in vivo. Collectively, our data suggest that KAF156, currently under evaluation in clinical trials, has the potential to treat, prevent, and block the transmission of malaria

Acquisition, Distribution and Perspectives of Healthcare Information in Complementary and Alternative Medicines (CAM)

Merged with duplicate record 10026.1/2500 on 06.20.2017 by CS (TIS)From April 2001 until September 2005 1 worked as a Pilkington research fellow at the Department of Complementary Medicine, University of Exeter, which in 2002 was integrated as a unit of the Peninsula Medical School. All the publications presented here have been carried out during my time of employment in this post at the Complementary Medicine Unit of the Peninsula Medical School in Exeter, United Kingdom. During the first few months of my research post in 2001 1 recognized the importance of the Internet as a tool to obtain healthcare information. Under the supervision of Professor Edzard Ernst, director of CAM, I carried out five Internet surveys, of which I collected and summarized the data and drafted the first version of the manuscripts, which were then finalized by Professor Ernst's comments: * Health risks over the Internet: advice offered by'medical herbalists' to a pregnant woman. * Reflexologists' responses to a patient with abdominal pain -a survey on Internet advice. * Internet advice by acupuncturists -a risk factor for cardiovascular patients? * Are asthma sufferers at risk when consulting chiropractors over the Internet? * Aspects of MMR / MMR vaccination advice over the Internet

Attention bias dynamics and symptom severity during and following CBT for social anxiety disorder

Objective: Threat-related attention bias figures prominently in contemporary accounts of the maintenance of anxiety disorders, yet longitudinal intervention research relating attention bias to anxiety symptom severity is limited. Capitalizing on recent advances in the conceptualization and measurement of attention bias, we aimed to examine the relation between attention bias, indexed using trial-level bias scores (TLBSs) to quantify temporal dynamics reflecting dysregulation of attentional processing of threat (as opposed to aggregated mean bias scores) and social anxiety symptom severity over the course of cognitive-behavioral therapy (CBT) and 1-month follow-up. Method: Adults with social anxiety disorder (N = 39) assigned to either yohimbine-or placebo-augmented CBT completed measures of attention bias and social anxiety symptom severity weekly throughout CBT (5 sessions) and at 1-week and 1-month posttreatment. Results: TLBSs of attention bias temporal dynamics showed stronger psychometric properties than mean aggregated scores and were highly interrelated, in line with within-subject temporal variability fluctuating in time between attentional overengagement and strategic avoidance from threat. Attention bias toward threat and temporal variability in attention bias (i.e., attentional dysregulation), but not attention bias away from threat, significantly reduced over the course of CBT. Cross-lag analyses revealed no evidence of a causal relation between reductions in attentional dysregulation leading to symptom severity reduction, or vice versa. Observed relations did not vary as a function of time. Conclusions: We found no evidence for attentional dysregulation as a causal mechanism for symptom reduction in CBT for social anxiety disorders. Implications for future research are discussed

Delivering a “Dose of Hope”: A Faith-Based Program to Increase Older African Americans’ Participation in Clinical Trials

Background: Underrepresentation of older-age racial and ethnic minorities in clinical research is a significant barrier to health in the United States, as it impedes medical research advancement of effective preventive and therapeutic strategies. Objective: The objective of the study was to develop and test the feasibility of a community-developed faith-based intervention and evaluate its potential to increase the number of older African Americans in clinical research. Methods: Using a cluster-randomized design, we worked with six matched churches to enroll at least 210 persons. We provided those in the intervention group churches with three educational sessions on the role of clinical trials in addressing health disparity topics, and those in the comparison group completed surveys at the same timepoints. All persons enrolled in the study received ongoing information via newsletters and direct outreach on an array of clinical studies seeking participants. We evaluated the short-, mid-, and longer-term effects of the interventional program on clinical trial-related outcomes (ie, screening and enrollment)