Pain palliation measurement in cancer clinical trials: the US Food and Drug Administration perspective.

BACKGROUND: Pain palliation resulting from antitumor therapy provides direct evidence of treatment benefit when combined with evidence of antitumor activity. The US Food and Drug Administration (FDA) previously issued guidance regarding the use of patient-reported outcome (PRO) measures to support labeling claims. The purpose of this article is to identify common challenges and key design strategies when measuring pain palliation in antitumor therapy clinical trials that are consistent with PRO Guidance principles. METHODS: Antitumor clinical protocols submitted to the FDA between 1995 and 2012 that included pain palliation as a primary or secondary endpoint were reviewed. Challenges in critical trial design components were identified. Design strategies consistent with PRO Guidance principles are proposed. RESULTS: The challenges identified were measurement of pain intensity and analgesic use, enrollment eligibility criteria, data collection methods, responder definitions, missing data, and blinding. Strategies included the use of well-defined, reliable, PRO assessments of pain intensity and analgesics; ensuring that enrollment criteria define patients with clinically significant pain attributable to cancer on an optimal analgesic regimen; defining responders using both pain and analgesic use criteria; incorporating an analysis of tumor response to support evidence of pain response; and minimizing missing data and inadvertent unblinding. CONCLUSIONS: Improvement in cancer-related pain resulting from antitumor therapy is an important treatment benefit that can support drug approval and labeling claims when adequately measured if study results demonstrate statistically and clinically significant findings. Sponsors are encouraged to discuss pain palliation assessment methods with the FDA early in and throughout product development.

Conceptual framework for behavioral and social science in HIV vaccine clinical research.

HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance.

Social and behavioral science in HIV vaccine trials: a gap assessment of the literature.

Social and behavioral science research is integral to the conduct of HIV vaccine trials, especially because the vaccine targets an infection laden with sensitive human issues. Although social and behavioral sciences have played a larger role in HIV vaccine clinical trials than other vaccine clinical trials to date, this role should be expanded. Fortunately, related publications, conference coverage and research proposals are on the rise; community engagement is receiving more attention during the earlier stages of product development; and collaboration between HIV vaccine scientists and social and behavioral scientists is being fostered. Greater attention to social and behavioral science issues could not only facilitate accrual, but also improve research efficiency and relevance. In this review, gaps in the literature on social and behavioral science issues in HIV vaccine clinical research, including barriers and facilitators to trial participation, enhancing feasibility of trial success, health systems, policy and monitoring social and behavioral issues, are identified and directions are suggested for filling those gaps. Development of a safe, efficacious and acceptable HIV vaccine will be nurtured by addressing the gaps through interdisciplinary collaborations.

Race/ethnicity: who is counting what?

Misclassification of race and ethnicity in administrative data may produce misleading results if it is overlooked or ignored. In this study, we examined the racial/ethnic classifications of 1,084 veterans with stroke in Florida who received inpatient and outpatient services within the Department of Veterans Affairs (VA) healthcare system and who were also eligible for Medicare between 2000 and 2001. We compared the reliability of racial/ethnic classifications between VA inpatient data, VA outpatient data, and Medicare data. Our results showed that (1) the rate of unknown racial/ethnic classification in VA outpatient and inpatient data was high, (2) minimizing the unknowns by substituting known values from other data when available would greatly enhance the overall and individual classification reliability, (3) black and white classifications in the VA data had stronger agreement with Medicare data, and (4) Medicare data may under-represent Hispanic patients.

Unidimensionality and bandwidth in the Center for Epidemiologic Studies Depression (CES-D) Scale.

In this study, we compared classical test theory (CTT) and item response theory (IRT) approaches in analyzing the Center for Epidemiological Studies Depression (CES-D) Scale (Radloff, 1977). Standard item analyses, as well as Rasch (1960) analyses, both revealed item departures from unidimensionality in a sample of 2,455 older persons responding to the CES-D. Positive affect items in the scale performed poorly overall, their removal reducing the scale's bandwidth only slightly. Modeling depression scores derived from Rasch measures and raw totals showed subtle but important differences for statistical inference. The assessment of depressive risk was slightly enhanced by using 16-item scale measures obtained from the results of the Rasch analysis as the dependent variable. Confirmatory factor analysis and parallel analysis verified the advantages of removing positively worded items. IRT and CTT techniques proved to be complementary in this study and can be usefully combined to improve measuring depression.

Ethnic disparities in stroke: epidemiology, acute care, and postacute outcomes.

BACKGROUND AND PURPOSE: Evidence for ethnic disparities in stroke incidence, severity, and mortality has continued to mount in recent years. However, the picture for disparities in acute management and rehabilitation remains more ambiguous. The objective of this report is to summarize current evidence from stroke epidemiology and studies focusing on disparities in stroke care and disability, suggesting courses for action. METHODS: A comprehensive search of current literature on ethnic/racial variation in stroke incidence, mortality, and severity, as well as acute and postacute patient care was performed. RESULTS: Recent evidence unambiguously reaffirms a greater burden of disease in stroke, greater mortality, and greater severity of strokes for blacks. Evidence for disparities in acute and postacute care is less conclusive, as is the evidence for disparities among other ethnic groups. Evidence for health disparities in stroke care across settings, regions, and the continuum of care varies considerably. CONCLUSIONS: Minority ethnic groups have higher rates or more severe stroke, but variations in prognosis for clinical outcomes other than mortality remain less certain. There is considerable need for more studies that take into account regional ethnic variations in treatment and outcomes, and for better documentation of stroke outcomes among groups in addition to blacks. Dealing with ethnic disparities in stroke will be served by sustained attention to quality improvement in high-impact areas in stroke care, complemented by initiatives that promote cultural competence.

Why ethnic designation matters for stroke rehabilitation: comparing VA administrative data and clinical records.

Using existing administrative data to look at issues of ethnic disparities in rehabilitation-related outcomes may lead to misleading results. Problems can emerge from apparently small issues of reliability that are magnified by reclassification of ethnic designation and missing data in complete-subject analyses. We compared the reliability of ethnic assignment in Department of Veterans Affairs (VA) medical rehabilitation records for stroke patients with administrative records; reclassified the racial identifier from the administrative data in two ways; and examined the different sources of ethnic information in relation to severity, length-of-stay, disability assessment, and discharge disposition. Our results show how small changes increase the potential for Type II error when describing ethnic differences in outcomes or using ethnicity as a predictor with dichotomous response variables. We discuss our results with reference to the literature on ethnic classification and underline the importance of initiatives for improved data collection on ethnicity in VA data sources and in rehabilitation research.

Risks, stigma and Honduran Garífuna conceptions of HIV/AIDS.

The HIV/AIDS epidemic along Honduras' north coast has intensified in recent years and become particularly severe in Garífuna communities. Based on a qualitative study in the community of Las Espinas and comparison with results from an earlier knowledge, attitudes, beliefs and practices survey, this article explores Garífuna ideas about the disease, focusing on issues of risk perception and stigma. Using correspondence analysis with data from systematic elicitation techniques we abstract the local schema of HIV/AIDS, showing how accurate knowledge of transmission co-occurs with cultural judgments about safe partners, increasing chances for infection. Despite broad familiarity with the disease in the community it remains highly stigmatized, suggesting continuing problems in coming to terms with the epidemic as treatment becomes more widely available in Honduras. Questions of power, sexuality and affective expectations about partners complicate the situation for women hoping to prevent infection. Given the broader risk environment characterized by labor migration and transnational movement, vital interventions and educational efforts in Garífuna communities will need to be complemented with prevention efforts in contexts where men make a living.

Gender schema and prostate cancer: veterans' cultural model of masculinity.

Coming to terms with disease, chronic illness, and aging may be challenging for men who adhere to an inflexible gender schema. In this study of elder U.S. veterans' ideas about masculinity, we find that prostate cancer patients reaffirm a strongly moral normalizing discourse about "being a man" yet tend to separate roles and values from male physical and sexual attributes. Using systematic data collection methods taken from cognitive anthropology, we map veterans' schema of masculinity and examine the relative importance that cancer patients and non-patients give to gender attributes. The results demonstrate the complementarity between cognitive and narrative approaches in medical anthropology. This research also suggests the hypotheses that (1) coming to terms with iatrogenesis may involve a subtle reformulation of masculinity and that (2) men with a fixed view of masculinity may have worse health outcomes than do those who accept the changes accompanying their treatment for prostate cancer.

Nutritional status of children undre 5 years of age in three hurricane-affected areas of Honduras / Estado nutricional de niños menores de 5 años en tres zona de Honduras azotadas por un huracán

Hurricanes and other natural disasters can produce crop destruction, population displacement, infrastructure damage, and long-term public health consequences that include increased malnutrition among the affected populations. This paper presents the results of anthropometric measurements taken of 295 children under 5 years of age from three regions of Honduras that were affected by Hurricane Mitch, a major storm that struck Central America in the fall of 1998. The children in our study were sampled in three shelters in the capital city of Tegucigalpa; in the resettlement zone of Nueva Choluteca, Choluteca; and in the small urban area of Catacamas, Olancho. Our data indicated that, in comparison to the period before the hurricane, there was an elevated prevalence of wasting in all three of the study areas, and that there were also high levels of underweight in the Tegucigalpa and Nueva Choluteca study areas. There were statistically significant differences between the mean values of malnutrition indicators for Catacamas and those for the Tegucigalpa and Nueva Choluteca settlements. These differences suggest that resettled families were confronting a nutritional crisis in July and August of 1999, some 9 months after the hurricane struck

Los huracanes y otros desastres naturales pueden destruir cosechas, desplazar a poblaciones enteras, causar daños infraestructurales y acarrear consecuencias a largo plazo para la salud pública, entre ellas un aumento de la desnutrición en las poblaciones afectadas. Este trabajo presenta los resultados de las mediciones antropométricas de 295 niños menores de 5 años de tres zonas de Honduras que fueron azotadas por el huracán Mitch, tempestad que azotó Centroamérica en el otoño de 1998. Los niños que participaron en nuestro estudio provinieron de tres alojamientos provisionales, uno en la capital del país, Tegucigalpa; otro en la zona de asentamiento para refugiados de Nueva Choluteca, Choluteca; y otro en la pequeña zona urbana de Catacamas, Olancho. Según indican nuestros datos, en comparación con el período anterior al huracán, la frecuencia de emaciación en las tres zonas fue alta, como también lo fue la de peso subnormal en las zonas de estudio de Tegucigalpa y Nueva Choluteca. Hubo diferencias estadísticamente significativas entre los valores promedio de los indicadores de desnutrición en Catacamas y los de los asentamientos de Tegucigalpa y Nueva Choluteca. Estas diferencias indican que las familias desplazadas enfrentaban una crisis nutricional en julio y agosto de 1999, alrededor de 9 meses después de la llegada del huracán

Estado nutricional de niños menores de cinco años de edad en tres regiones de Honduras después del huracán Mitch

Este artículo presenta información antropométrica que describe el estado nutricional de tres poblaciones hondureñas afectadas por el huracán Mitch. Se presenta un análisis de medidas de peso y talla de 295 niños menores de 5 años de edad. Las medidas fueron tomadas en los departamentos de Choluteca, Olancho y en el área urbana de Tegucigalpa. Los resultados muestran un aumento significativo de la prevalencia de desnutrición aguda y crónica, en comparación a los niveles previos al desastre. La discusión teórica de estos datos toma una perspectiva de ecología política, y sugiere que el notable aumento de la desnutrición es el resultado de la conjunción de factores políticos, ambientales y sociales.(AU)