Assessing the Financial Value of Patient Engagement: A Quantitative Approach from CTTI's Patient Groups and Clinical Trials Project.

BACKGROUND: While patient groups, regulators, and sponsors are increasingly considering engaging with patients in the design and conduct of clinical development programs, sponsors are often reluctant to go beyond pilot programs because of uncertainty in the return on investment. We developed an approach to estimate the financial value of patient engagement. METHODS: Expected net present value (ENPV) is a common technique that integrates the key business drivers of cost, time, revenue, and risk into a summary metric for project strategy and portfolio decisions. We assessed the impact of patient engagement on ENPV for a typical oncology development program entering phase 2 or phase 3. RESULTS: For a pre-phase 2 project, the cumulative impact of a patient engagement activity that avoids one protocol amendment and improves enrollment, adherence, and retention is an increase in net present value (NPV) of $62MM ($65MM for pre-phase 3) and an increase in ENPV of $35MM ($75MM for pre-phase 3). Compared with an investment of $100,000 in patient engagement, the NPV and ENPV increases can exceed 500-fold the investment. This ENPV increase is the equivalent of accelerating a pre-phase 2 product launch by 2½ years (1½ years for pre-phase 3). CONCLUSIONS: Risk-adjusted financial models can assess the impact of patient engagement. A combination of empirical data and subjective parameter estimates shows that engagement activities with the potential to avoid protocol amendments and/or improve enrollment, adherence, and retention may add considerable financial value. This approach can help sponsors assess patient engagement investment decisions.

A nationwide epidemiologic modeling study of LD: risk, protection, and unintended impact.

Through multiple logistic regression modeling, this article explores the relative importance of risk and protective factors associated with learning disabilities (LD). A representative national sample of 6- to 17-year-old students (N = 1,268) was drawn by random stratification and classified by the presence versus absence of LD in reading, spelling, and mathematics according to ability-achievement discrepancies or low achievement levels. The dichotomous classifications were regressed on sets of explanatory variables indicating potential biological, social-environmental, and cognitive factors, problem behavior, and classroom learning behavior. Modeling revealed patterns of high risk for male students and students evincing verbal and nonverbal ability problems and processing speed problems. It was shown that, absent controls for cognitive abilities (such as provided by the ability-achievement discrepancy definition), definitions keyed to low achievement will substantially overidentify ethnic minority and disadvantaged students and will be confounded by significantly higher proportions of students who display oppositional and aggressive behavior problems. Alternatively, good learning behaviors uniformly provide substantial reduction in the risk for LD.

Transcriptional profiling of mefloquine-induced disruption of calcium homeostasis in neurons in vitro.

Mefloquine is associated with adverse neurological effects that are mediated via unknown mechanisms. Recent in vitro studies have shown that mefloquine disrupts neuronal calcium homeostasis via liberation of the endoplasmic reticulum (ER) store and induction of calcium influx across the plasma membrane. In the present study, global changes in gene expression induced in neurons in response to mefloquine-induced disruption of calcium homeostasis and appropriate control agents were investigated in vitro using Affymetrix arrays. The mefloquine transcriptome was found to be enriched for important regulatory sequences of the unfolded protein response and the drug was also found to induce key ER stress proteins, albeit in a manner dissimilar to, and at higher equivalent concentrations than, known ER-tropic agents like thapsigargin. Mefloquine also down-regulated several important functional categories of genes, including transcripts encoding G proteins and ion channels. These effects may be related to intrusion of extracellular calcium since they were also observed after glutamate, but not thapsigargin, hydrogen peroxide, or low-dose mefloquine treatment. Mefloquine could be successfully differentiated from other treatments on the basis of principle component analysis of its "calcium-relevant" transcriptome. These data may aid interpretation of expression of results from future in vivo studies.

Neonatal staff and advanced practice nurses' perceptions of bereavement/end-of-life care of families of critically ill and/or dying infants.

BACKGROUND: Parents need compassionate care when an infant dies. Nurses can provide such care and possibly facilitate grieving, yet often have inadequate preparation in bereavement/end-of-life care. OBJECTIVE: To describe neonatal nurses' perceptions of bereavement/end-of-life care of families of critically ill and/or dying infants. METHODS: A cross-sectional, descriptive, correlational mailed survey design was used. The 55-item Bereavement End-of-Life Attitudes About Care: Neonatal Nurses Scale containing 4 sections (comfort, roles, involvement, and demographics) was mailed to 240 hospitals in the United States. RESULTS: The final response rate was 52% (190 completed data sets from 125 hospitals). Respondents were comfortable with many aspects of bereavement/end-of-life care. Comfort and roles scores correlated significantly with number of years as a neonatal intensive care nurse. Respondents agreed about many important aspects of their roles with patients' families, especially the importance of providing daily support to the families. Most respondents identified caring for a dying infant, the actual death of an infant, and language or cultural differences as influential factors in the level of their involvement with families. CONCLUSIONS: Education on bereavement/end-of-life care could affect nurses' comfort with caring for families of critically ill and/or dying infants. Additional education on cultural competence would be helpful. Educators must promote the inclusion of content on bereavement/end-of-life care in nursing curricula. Finally, researchers must focus more attention on factors that promote and inhibit bereavement/end-of-life care of families of critically ill and/or dying infants.