The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials.

Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials. The recent increase in pragmatic clinical trials raises at least two questions about this approach. First, is exclusion itself a harm to vulnerable populations, as these groups may be denied access to understanding how health interventions work for them in clinical settings? Second, are groups considered vulnerable in traditional clinical trials also vulnerable in pragmatic clinical trials? We argue first that excluding vulnerable subjects from participation in pragmatic clinical trials can be harmful by preventing acquisition of data to meaningfully inform clinical decision-making in the future. Second, we argue that protections for vulnerable subjects in traditional clinical trial settings may not be translatable, feasible, or even ethical to apply in pragmatic clinical trials. We conclude by offering specific recommendations for appropriately protecting vulnerable research subjects in pragmatic clinical trials, focusing on pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons.

Privacy and confidentiality in pragmatic clinical trials.

With pragmatic clinical trials, an opportunity exists to answer important questions about the relative risks, burdens, and benefits of therapeutic interventions. However, concerns about protecting the privacy of this information are significant and must be balanced with the imperative to learn from the data gathered in routine clinical practice. Traditional privacy protections for research uses of identifiable information rely disproportionately on informed consent or authorizations, based on a presumption that this is necessary to fulfill ethical principles of respect for persons. But frequently, the ideal of informed consent is not realized in its implementation. Moreover, the principle of respect for persons­which encompasses their interests in health information privacy­can be honored through other mechanisms. Data anonymization also plays a role in protecting privacy but is not suitable for all research, particularly pragmatic clinical trials. In this article, we explore both the ethical foundation and regulatory framework intended to protect privacy in pragmatic clinical trials. We then review examples of novel approaches to respecting persons in research that may have the added benefit of honoring patient privacy considerations.

Bilingual Text Messaging Translation: Translating Text Messages From English Into Spanish for the Text4Walking Program.

BACKGROUND: Hispanic adults in the United States are at particular risk for diabetes and inadequate blood pressure control. Physical activity improves these health problems; however Hispanic adults also have a low rate of recommended aerobic physical activity. To address improving physical inactivity, one area of rapidly growing technology that can be utilized is text messaging (short message service, SMS). A physical activity research team, Text4Walking, had previously developed an initial database of motivational physical activity text messages in English that could be used for physical activity text messaging interventions. However, the team needed to translate these existing English physical activity text messages into Spanish in order to have culturally meaningful and useful text messages for those adults within the Hispanic population who would prefer to receive text messages in Spanish. OBJECTIVE: The aim of this study was to translate a database of English motivational physical activity messages into Spanish and review these text messages with a group of Spanish speaking adults to inform the use of these text messages in an intervention study. METHODS: The consent form and study documents, including the existing English physical activity text messages, were translated from English into Spanish, and received translation certification as well as Institutional Review Board approval. The translated text messages were placed into PowerPoint, accompanied by a set of culturally appropriate photos depicting barriers to walking, as well as walking scenarios. At the focus group, eligibility criteria for this study included being an adult between 30 to 65 years old who spoke Spanish as their primary language. After a general group introduction, participants were placed into smaller groups of two or three. Each small group was asked to review a segment of the translated text messages for accuracy and meaningfulness. After the break out, the group was brought back together to review the text messages. RESULTS: A translation confirmation group met at a church site in an urban community with a large population of Hispanics. Spanish speaking adults (N=8), with a mean age of 40 (SD 6.3), participated in the study. Participants were engaged in the group and viewed the text messages as culturally appropriate. They also thought that text messages could motivate them to walk more. Twenty-two new text messages were added to the original database of 246 translated text messages. While the text messages were generally understood, specific word preferences were seen related to personal preference, dialect, and level of formality which resulted in minor revisions to four text messages. CONCLUSIONS: The English text messages were successfully translated into Spanish by a bilingual research staff and reviewed by Hispanic participants in order to inform the use of these text messages for future intervention studies. These Spanish text messages were recently used in a Text4Walking intervention study.

Demographic characteristics of U.S. Chinese older adults in the Greater Chicago area: assessing the representativeness of the PINE study.

OBJECTIVE: We aimed to assess the representativeness of the demographic characteristics of the PINE study to the Chinese aging population in the Greater Chicago area. METHOD: The PINE study is a population-based study of Chinese older adults aged 60 and over in the Greater Chicago area. In preparation of the PINE study, we conducted a random block census study in Chicago. Demographic characteristics of the PINE study were compared with the data drawn from U.S. Census 2010 and random block census study using chi-square tests. RESULTS: The PINE study is representative of the Chinese aging population in the Greater Chicago area. No significant difference was found in key attributes including age, sex, income, education, number of children, and country of origin. DISCUSSION: Our report is critical in understanding the vast socio-demographic diversity of U.S. Chinese older adults. Rigorous studies are needed to explore the heterogeneity among the diverse aging populations.

Cost-effectiveness of transcranial magnetic stimulation in the treatment of major depression: a health economics analysis.

INTRODUCTION: Transcranial magnetic stimulation (TMS) is a novel antidepressant therapy shown to be effective and safe in pharmacotherapy-resistant major depression. The incremental cost-effectiveness and the direct cost burden compared with sham treatment were estimated, and compared with the current standard of care. METHODS: Healthcare resource utilization data were collected during a multicenter study (n=301) and a decision analysis was used to stratify the 9-week treatment outcomes. A Markov model with an acute-outcome severity-based risk of relapse was used to estimate the illness course over a full year of treatment follow-up. These model estimates were also compared to best estimates of outcomes and costs of pharmacotherapy treatment, using the published STAR(*)D outcomes. The cost-effectiveness of TMS was described using an incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained and on a direct cost per patient basis across a varying range of assumptions. The model's sensitivities to costs due to losses in work productivity and to caregiver time were also examined. RESULTS: Compared with sham treatment and at a cost of US$300 per treatment session, TMS provides an ICER of US$34,999 per QALY, which is less than the "willingness-to-pay' standard of US$50,000 per QALY for a new treatment for major depression. When productivity gains due to clinical recovery were included, the ICER was reduced to US$6667 per QALY. In open-label conditions, TMS provided a net cost saving of US$1123 per QALY when compared with the current standard of care. In the openlabel condition, cost savings increased further when the costs for productivity losses were included in the model (net savings of US$7621). The overall cost benefits of treating MD using TMS were greater in those patients at the earliest levels of treatment resistance in the overall sample. CONCLUSION: TMS is a cost-effective treatment for patients who have failed to receive sufficient benefit from initial antidepressant pharmacotherapy. When used at earlier levels of treatment resistance, significant cost savings may be expected relative to the current standard of care.