Credibility and comprehension of healthy volunteers in lengthy inpatient drug studies.

Early clinical trials rely upon paid healthy volunteers. Concern has been raised regarding the characteristics of these individuals, how well they understand their rights and the risks of clinical research, and how they may be influenced by manipulation or coercion. Therefore, we investigated (1) the motivations of subjects in clinical trials, (2) how well these individuals comprehend a consent form they sign, and (3) the effect of the stipend on the reliability of information reported by volunteers in clinical trials. Thirty healthy subjects (age, 21-45 years) in a long-duration clinical trial were administered a questionnaire gathering demographic information and testing their comprehension of the consent form. In a separate chart review of 10 clinical trials, 374 subjects were studied to determine their reliability in reporting abnormalities in their medical history and in reporting adverse events, and an association was examined between the incidence of unreliable reporting and the stipend paid to them for participating in the clinical trial. A large percentage of subjects who were enrolled in the long-duration clinical trial failed to comprehend a variety of basic concepts related to the consent form and their participation in the drug study. The chart review demonstrated that subjects who are paid larger stipends may not be more likely to report abnormalities on their medical history. Further studies should be undertaken with larger numbers of subjects enrolled in clinical trials, and possible associations between demographic data (eg, income, level of education, number of previous studies) and the reliability of information provided by normal healthy research volunteers should be examined.

Psychotropic drugs and paediatrics: a critical need for more clinical trials.

Many children in the USA are prescribed psychotropic drugs that have not been fully investigated in paediatric clinical trials. The common practice of prescribing psychotropic drugs off-label poses unknown and potentially serious short- and long-term consequences for these children. This paper briefly reviews the factors associated with the lack of paediatric clinical trials. We advocate a shift toward increasing paediatric trials with psychotropic drugs through a combination of adequate safety controls, additional reimbursement/compensation, a more organised and large-scale effort to collate results and outcomes across researchers and studies and additional public education about the importance of this research. In addition, we encourage the re-examination of the ethical standards for children's participation in phase 1 clinical trials as well as argue for longitudinal developmental studies on children who are prescribed off-label psychotropic drugs.

Are normal healthy research volunteers psychologically healthy? A pilot investigation.

Most new drug development in Phase I clinical trials relies on the use of "normal healthy research volunteers" (NHRVs); however, little is known about the personality functioning of these volunteers. Determining whether NHRVs are similar to or different from individuals with "normal" personalities can impact participant recruitment, group assignment, and statistical interpretation of study results. This pilot study was undertaken to gain insight into the demographics, personality functioning, and potential psychopathology of the volunteers who participated in a Phase I confinement clinical drug trial. NHRVs (N=28) in an all-male, Phase I clinical trial completed a battery of questions, including the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and a sociodemographic questionnaire. Fifty percent of the sample showed clinically significant elevations on at least one of the scales. Current findings need to be replicated and expanded through future research. Results must be interpreted with caution because of the small, all-male sample. This preliminary study suggests that there is a difference in personality functioning between NHRVs and the general population. In addition, NHRVs may purposefully distort or conceal self-report information when participating in studies.

Personality profiles of normal healthy research volunteers: a potential concern for clinical drug trial investigators?

"Normal healthy research volunteers" (NHRVs) in Phase I clinical trials are utilized to provide precise pharmacokinetic information and subjective self-reports to help determine the initial drug dose for future Phase II, III, and IV trials, and accurate dose levels for future use in a patient population. Medical researchers rely on both objective pharmacokinetic and subjective data from NHRVs. Research shows that personality characteristics can influence these results in Phase I clinical trials. For example, extroverted personality characteristics have influenced the subjective reports and physiological experience of NHRVs. Second, subjective responses to placebos have been significantly greater in extroverted NHRVs than in introverted NHRVs. Third, in looking at Type-A and Type-B personality characteristics, NHRVs with Type-A Characteristics reported significantly more negative side effects to placebos than did people with Type-B characteristics. Fourth, NHRVs with high anxiety had more reports of adverse symptoms after drug administration than NHRVs with low anxiety. Further, it has been found that gastric emptying occurs more rapidly in people with high levels of neuroticism as compared to people with low levels of neuroticism. The authors suggest that personality and psychological characteristics of NHRVs can influence pharmacokinetic results and thus need to be addressed either in the statistical analysis or in the screening process for NHRV studies. Suggestions for further research and analysis are included, along with ideas for a national volunteer subject pool for NHRVs.

The recruitment of normal healthy volunteers: a review of the literature on the use of financial incentives.

Unresolved issues of ethical, methodological, and legal concerns in the use of normal healthy volunteers persist. Financial incentives in their recruitment offer a unique ethical dilemma because of questions surrounding payment. A review of literature was conducted to obtain research systematically examining volunteer motivation and the role offinancial incentives. The primary selection criterion was motivation and payment to volunteers; seven studies met the criterion for review. Studies that have systematically investigated volunteer motivation have found financial rewards to be an important motivator among normal healthy volunteers in their decision to participate in clinical trials. Also evident is that differences based on demographic characteristics exist in the motivation and rates of volunteerism. Ethical issues surrounding the use of normal healthy volunteers are discussed, with attention to the issue offinancial incentives (e.g., economically vulnerable volunteers, undue inducements). Regulations, guidelines, and recommendations are discussed with regard to volunteers and financial incentives.

Is domestic violence relevant?: An exploratory analysis of couples referred for mediation in family court.

Mediation is an essential component of custody evaluation and reconciliation services in domestic courts. Data from 306 couples with and without a reported history of domestic violence (DV) who were ordered to attend an assessment for mediation were analyzed to determine differences in the mediation process. More than one third reported a history of DV. Chi-square analysis showed that differences in the mediation process exist between couples reporting DV and couples reporting no DV. A greater proportion of couples with reported DV (a) actually attended the court-mandated assessment session, (b) were deemed unsuitable to participate in the mediation process, (c) were in default of child-support payments, and (d) reported drug and alcohol abuse. No significant differences were found between the two groups in the measured mediation outcomes. Implications for the use of mediation with couples who reported DV and recommendations for future research are discussed.

The assessment and management of the violent patient in critical hospital settings.

OBJECTIVE: Patient violence and aggression is prevalent in critical care settings, yet clinicians are often inadequately trained to assess and respond to these types of behaviors. Targeted toward trainees as well as seasoned clinicians, this articles provides an updated review of the literature regarding the management of violence in the emergency department. METHODS: This narrative review is largely derived from research articles and reviews published since 2000. We conducted a systematic search of electronic databases for review articles or studies examining patient violence and aggression in critical care settings. Electronic searches were supplemented by manual searches of reference lists. RESULTS: Current statistics, risk factors and imminent signs of violent patient behavior are presented. We conclude with recommendations for pharmacological and psychological interventions that can help manage aggressive behavior in the emergency department. CONCLUSIONS: The relatively high frequency of aggressive and violent behavior in critical care settings increases the likelihood that clinicians working in this environment will encounter this situation. It is our hope that providing additional information about the factors associated with and techniques for managing violent patient behavior will reduce the occurrence of injuries in health care professionals in emergency departments.

Pediatric drug-trial recruitment: enticement without coercion.

Despite federal initiatives to increase research and expand data about the effectiveness and safety of medications in children, data are still limited for this population. One of the most salient barriers to conducting pediatric clinical trials involves participant recruitment. In this article, we summarize recruitment challenges including a lack of research infrastructure, the need to properly define appropriate use of incentives and payments, and inconsistencies in the current use of payments and incentives. We also searched the Centerwatch.com and ClinicalTrials.gov databases for updated data on current practices in pediatric participant compensation/payment. We provide recommendations for tackling current barriers to recruiting and retaining children and families in clinical trials.

Inpatient suicide: preventing a common sentinel event.

OBJECTIVE: Suicide in the hospital is one of the most common types of sentinel events, and hospitals can (and should) take steps to decrease the likelihood of experiencing this type of crisis. METHOD: MEDLINE, Cochrane Library, National Electronic Library for Mental Health, and PSYCHINFO searches were conducted. In addition, manual and phone queries were used to identify relevant empirical and clinical publications. Reference sections of published articles were also searched. RESULTS: The current article discusses the rates of suicide in hospitals, related risk factors, methods of suicidal behavior, and factors which contribute to this tragic event. Environmental, patient care, staff training, and hospital policy recommendations for decreasing the number of inpatient suicides are presented. CONCLUSION: Inpatient suicide is a traumatic event. Although it is a relatively rare occurrence that is often difficult to predict and prevent, continuing to refine our efforts to assist the population at risk is imperative.

Suicidal behavior in children younger than twelve: a diagnostic challenge for emergency department personnel.

Suicide is one of the leading causes of death in children younger than 12 years and is the fourth leading cause of death in 12 year olds. Increasing numbers of young children now present to the emergency department (ED) with mental health issues, and ED personnel must determine the most appropriate disposition options for these children, sometimes without the assistance of specialty mental health services. Much of the present body of literature describing suicidality fails to separate children from adolescents for analysis and discussion. This article reviews relevant literature pertaining to suicidal thoughts and behaviors in young children and discusses problems with available data, as well as epidemiology, risk factors, typical motivations, methods, assessment, and disposition for these patients. Suicidal children younger than 12 years are often clinically different from suicidal adolescents and adults and may require unique assessment and disposition strategies in the ED. A child who has ideation without a clear plan, or has made an attempt of low lethality, can sometimes be discharged home, provided that a supportive, responsible caregiver is willing to monitor the child and take him or her to outpatient mental health appointments. If the home environment is detrimental, or the child has used a method of high potential lethality, inpatient treatment is the most appropriate course of action. Mental health specialty services, when available, should be used to help determine the most appropriate disposition.

Repeat participation among normal healthy research volunteers: professional guinea pigs in clinical trials?

The recent death of a normal healthy volunteer, as well as the increased use of normal volunteers as research subjects, has heightened the attention given to the participation of normal volunteers in clinical research. An overlooked sub-population of normal healthy volunteers are repeat, veteran volunteers. This essay discusses ethical and methodological issues associated with the use of repeat volunteers in research, along with existing guidelines regarding the use of repeat healthy volunteers, and concludes with recommendations for safeguarding repeat volunteers and ideas supporting centralized recruiting.

Ethical parameters of challenge studies inducing psychosis with ketamine.

Researchers routinely induce psychosis in healthy volunteers via ketamine infusion to expand their knowledge of schizophrenia. We question the ethics of the nature and procedures of such studies. We also address safeguards for ethically conducting and reporting such pursuits, including recruitment, screening, available treatment, and follow-up.