Teresa Edwards

US academic drug discovery

Progress in the biomedical sciences has accelerated enormously over the last two decades. Technology to enable discovery of ligands to perturb the function of biological targets has also advanced such that many complementary approaches exist for creating small molecule tools to interrogate biological processes and potentially serve as drug leads.1 However, while pharmaceutical industry investment in R&D has grown exponentially, approval of new medicines has remained constant2 and pricing pressures and litigation have further eroded profitability.3 Frequent mergers, reorganizations and reductions in scientific staff in the for-profit drug discovery sector have made it increasingly difficult for a research project or strategy to bear fruit before it is abandoned for nontechnical reasons.4 As a result, there is a growing trend for large pharmaceutical companies to externalize the early phases of drug discovery via either active partnerships or opportunistic in-licensing of novel compounds. In this context, there is a clear societal need for enhanced innovation and productivity in drug discovery in order for advances in biomedical research to result in new medicines. Academia is a critical area where innovation in drug discovery can flourish. Indeed, two recent reviews provided strong support for the role of academics and biotechnology companies (often spawned from academia) in producing 56% of the new small molecule and biologic drugs judged by the FDA to warrant priority review in the period spanning 1998-2007.5, 6 While over the years individual investigators in academia have been successful at small molecule drug discovery, the conditions outlined above have led to more formal academic drug discovery (ADD) efforts during the last decade. This trend has been noted and a number of scientists engaged in this endeavor have provided commentary on the emerging field.7-11 However, the analyses to date have relied almost exclusively on expert opinion and very rarely upon data. In the current article we report the results of a scientific survey of academic and non-profit drug discovery entities in the United States and our analysis of the current state of this enterprise and prospects for the future. We intentionally excluded work on large molecules such as monoclonal antibodies or siRNA because our intent was to capture the emerging trend of systematic focus on small molecule drug discovery. To accomplish this we utilized survey methodology currently employed in organizational and general social science research, as described in the Supplementary Materials. Seventy-eight units were identified as small molecule drug discovery centers sited within universities or non-profit research organizations and our response rate was 71% which compares very favorably to average response rates in web surveys.

Stewardship Practices of U.S. Biobanks

Most U.S. biobanks do not create ongoing relationships with contributors but do practice stewardship over storing and sharing of specimens. Biobanks require new governance models that address their ethical and regulatory challenges. One model relies on stewardship of specimens throughout their life course. Here, we discuss findings from our survey of 456 U.S. biobank managers that addressed whether and how biobanks steward their specimens. The findings reveal that most biobanks do not create ongoing relationships with contributors but do practice stewardship over storing and sharing of specimens. Biobanks now need guidance to fully articulate stewardship practices that ensure respect for contributors while facilitating research.

Suboptimal Surveillance for and Knowledge of Hepatocellular Carcinoma Among Primary Care Providers

BACKGROUND & AIMS A large proportion of patients with cirrhosis are seen only by their primary care provider (PCP). Surveillance for hepatocellular carcinoma (HCC) therefore depends on PCPs in these cases. We aimed to assess PCP knowledge and practice of HCC surveillance. METHODS We contacted a random sample of 1000 North Carolina PCPs by mail. All PCPs contacted received an introductory letter followed by a 12-item questionnaire addressing HCC surveillance knowledge and practice. RESULTS A total of 391 PCPs (39%) completed the survey; 89% saw patients with cirrhosis in their practice, but only 45% screened for HCC. Among PCPs who screened for HCC, the most common methods were ultrasound analysis and measurement of α-fetoprotein level (66%). Reasons for surveillance included supported by evidence (72%), recommended by medical societies (42%), and malpractice liability for not performing surveillance (26%). Of PCPs who did not screen, 84% referred to gastroenterologists for surveillance decisions, 24% were unaware of recommendations, 8% were uncertain of the benefits, and 8% were concerned about cost. Hepatic resection and liver transplantation were identified as effective therapies by 67% and 56% of PCPs, respectively, but all other effective therapies were identified by less than half (transarterial chemoembolization by 42%, radiofrequency ablation by 35%, and sorafenib by 26%). The ability to identify at least 1 effective therapy was associated independently with surveillance (odds ratio, 2.1; 95% confidence interval, 1.1-4.0). CONCLUSIONS Most PCPs see patients with cirrhosis, but only a minority screen for HCC. PCP knowledge of effective HCC therapy options is suboptimal. Efforts to enlist PCPs in HCC surveillance may be best served by increasing their knowledge of effective therapies.

Does an offer for a free on-line continuing medical education (CME) activity increase physician survey response rate? A randomized trial

BackgroundAchieving a high response rate in a physician survey is challenging. Monetary incentives increase response rates but obviously add cost to a survey project. We wondered whether an offer of a free continuing medical education (CME) activity would be effective in improving survey response rate.ResultsAs part of a survey of a national sample of physicians, we randomized half to an offer for a free on-line CME activity upon completion of a web-based survey and the other half to no such offer. We compared response rates between the groups. A total of 1214 out of 8477 potentially eligible physicians responded to our survey, for an overall response rate of 14.3%. The response rate among the control group (no offer of CME credit) was 16.6%, while among those offered the CME opportunity, the response rate was 12.0% (p < 0.0001).ConclusionsAn offer for a free on-line CME activity did not improve physician survey response rate. On the contrary, the offer for a free CME activity actually appeared to worsen the response rate.

Overlooked and underserved: Widowed fathers with dependent-age children

OBJECTIVE Widowed fathers and their children are at heightened risk for poor coping and maladaptive psychosocial outcomes. This exploratory study is the first to explicitly examine the psychological characteristics of this population of fathers. METHOD Some 259 fathers (mean age = 46.81; 90% Caucasian) with dependent-age children and whose wives had died from cancer within the previous five years completed a web-based survey that consisted of demographic questions, the Center for Epidemiologic Studies Depression Scale (CES-D), the Texas Inventory of Grief-Revised (TRIG-R), the Psychological Adaptation Scale (PAS), the Kansas Parental Satisfaction Scale (KPSS), and items assessing perceived parental efficacy. RESULTS Fathers were found to have elevated depressive (CES-D mean = 22.6) and grief (TRIG-R mean = 70.3) symptomatology, low adaptation (PAS mean = 3.2), and high levels of stress related to their parenting role. They reported being satisfied with their parenting (KPSS mean = 15.8) and having met their own parental expectations. Multivariate analyses revealed an association between fathers age and depression (p = <0.01), with younger fathers reporting greater depressive symptoms. Psychological adaptation was positively correlated with being in a romantic relationship (p = 0.02) and age of oldest child (p = 0.02). SIGNIFICANCE OF RESULTS The results of our exploratory study suggest that, while widowed fathers perceive themselves as meeting their parental responsibilities, it comes at a substantial psychological cost, with particularly high stress related to being a sole parent. These findings may help guide interventions for this neglected population and underscore the importance of developing targeted therapies and research protocols to address their needs.

End-of-life experiences of mothers with advanced cancer: perspectives of widowed fathers.

Objective Despite the importance of parenting-related responsibilities for adult patients with terminal illnesses who have dependent children, little is known about the psychological concerns of dying parents and their families at the end of life (EOL). The aim of this study was to elicit widowed fathers’ perspectives on how parental status may have influenced the EOL experiences of mothers with advanced cancer. Subjects 344 men identified themselves through an open-access educational website as widowed fathers who had lost a spouse to cancer and were raising dependent children. Methods Participants completed a web-based survey about their wifes EOL experience and cancer history, and their own depression (Center for Epidemiologic Studies Depression Scale, CES-D) and bereavement (Texas Revised Inventory of Grief, TRIG) symptoms. Descriptive statistics, Fishers exact tests, and linear regression modelling were used to evaluate relationships between variables. Results According to fathers, 38% of mothers had not said goodbye to their children before death and 26% were not at all ‘at peace with dying.’ Ninety per cent of widowed fathers reported that their spouse was worried about the strain on their children at the EOL. Fathers who reported clearer prognostic communication between wife and physician had lower CES-D and TRIG scores. Conclusions To improve EOL care for seriously ill patients and their families, we must understand the concerns of parents with dependent children. These data underscore the importance of parenting-related worries in this population and the need for additional clinical and research programmes devoted to addressing these issues.

An exploratory study of end-of-life prognostic communication needs as reported by widowed fathers due to cancer

Effective physician communication about prognosis is a critical aspect of quality care for families affected by terminal illness. This is particularly important for spousal caregivers of terminally ill parents of dependent children, who may have unique needs for communication about anticipated death. The objective of this study was to explore end‐of‐life prognostic communication experiences reported by bereaved fathers whose wives died from cancer.

Widowed parenting self-efficacy scale: A new measure

ABSTRACT The authors developed and tested a novel measure of parenting self-efficacy specifically for recently widowed parents of dependent-age children. They tested the scale among 244 recently widowed fathers via an open-access web survey. Exploratory factor analysis identified 3 factors: perception of meeting parenting expectations (α = .88), provision of effective discipline (α = .69), and sense of parental burden (α = .69). Scores on the new scale correlated positively with Kansas Parenting Satisfaction and Psychological Adaptation Scale scores, and negatively with CES-D (depression) and TRIG (grief) scale scores. The resulting 9-item Widowed Parenting Self Efficacy Scale is a promising measure for use in research and clinical settings.