Krista Tromp

Psychological, behavioral and social effects of disclosing Alzheimer's disease biomarkers to research participants: a systematic review

BackgroundCurrent Alzheimer’s disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants.MethodsWe performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group.ResultsFourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning.ConclusionIn cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed.Trial registrationPROSPERO international prospective register for systematic reviews CRD42016035388. Registered 19 February 2016.

Ethics of Drug Research in the Pediatric Intensive Care Unit

Critical illness and treatment modalities change pharmacokinetics and pharmacodynamics of medications used in critically ill children, in addition to age-related changes in drug disposition and effect. Hence, to ensure effective and safe drug therapy, research in this population is urgently needed. However, conducting research in the vulnerable population of the pediatric intensive care unit (PICU) presents with ethical challenges. This article addresses the main ethical issues specific to drug research in these critically ill children and proposes several solutions. The extraordinary environment of the PICU raises specific challenges to the design and conduct of research. The need for proxy consent of parents (or legal guardians) and the stress-inducing physical environment may threaten informed consent. The informed consent process is challenging because emergency research reduces or even eliminates the time to seek consent. Moreover, parental anxiety may impede adequate understanding and generate misconceptions. Alternative forms of consent have been developed taking into account the unpredictable reality of the acute critical care environment. As with any research in children, the burden and risk should be minimized. Recent developments in sample collection and analysis as well as pharmacokinetic analysis should be considered in the design of studies. Despite the difficulties inherent to drug research in critically ill children, methods are available to conduct ethically sound research resulting in relevant and generalizable data. This should motivate the PICU community to commit to drug research to ultimately provide the right drug at the right dose for every individual child.

Motivations of children and their parents to participate in drug research: a systematic review

ABSTRACTInformation on motivations for research participation, may enable professionals to better tailor the process of recruitment and informed consent to the perspective of parents and children. Therefore, this systematic review assesses motivating and discouraging factors for children and their parents to decide to participate in clinical drug research. Studies were identified from searches in 6 databases. Two independent reviewers screened and selected relevant articles. Results were aggregated and presented by use of qualitative metasummary. 38 studies fulfilled the selection criteria and were of sufficient quality for inclusion in the qualitative metasummary. Most mentioned motivating factors for parents were: health benefit for child, altruism, trust in research, and relation to researcher. Most mentioned motivating factors for children were: personal health benefit, altruism and increasing comfort. Fear of risks, distrust in research, logistical aspects and disruption of daily life were mentioned most by parents as discouraging factors. Burden and disruption of daily life, feeling like a “guinea pig” and fear of risks were most mentioned as discouraging factors by children. Conclusion: Paying attention to these motivating and discouraging factors of children and their parents during the recruitment and informed consent process in drug research increases the moral and instrumental value of informed consent.What is known:• This systematic review pools the existing empirical literature on motivations of minors and their parents to consent or dissent to participation in clinical drug research.• The most mentioned motivating and discouraging factors for children and their parents to consent to participation in clinical drug research are identified aggregated and presented by use of qualitative metasummary.What is new:• This information can be used to adapt the research protocol, recruitment, and informed consent/assent process to the needs of children and their parents.

Gatekeeping by Professionals in Recruitment of Pediatric Research Participants: Indeed an Undesirable Practice

Luchtenberg and colleagues (2015) bring their interesting article to a close with the concluding statement that professionals should not be reluctant to ask young people to participate in clinical ...

Patients' Trust as Fundament for Research Ethics Boards

Kraft and colleagues make a convincing plea for the importance of trustworthiness and trusting relationships between patient-participants and research professionals in medical research in their interesting article (Kraft et al. 2018). However, we do not agree with the authors that their findings concerning patients’ trust challenge the current model of research ethics, “because that model is primarily focused on supporting individual autonomy”; to the contrary, we think it underbuilds the current research system. Although Kraft and colleagues specifically researched trust in biobank research among ethnically and culturally diverse groups, we also found trust to be of major importance in members of an average Dutch population who were asked for participation in a clinical trial. We interviewed parents and their children about their willingness to participate in clinical research, after observing informed-consent conversations between them and research professionals. We wanted to know: What motivated them to participate, and what influenced their decision? Trust was one of the main issues that was put forward by them as an influencing factor. In this commentary we want to share our results and corroborate the results presented by Kraft and colleagues. But we also want to point out that we draw partially different conclusions from these results.

Trial recruitment in the pediatric intensive care: Ask consent before you start?!

To the Editor: We read with great interest the article published in a recent issue of Critical Care Medicine by Ventura et al (1) on their randomized controlled trial (RCT) comparing the effect of first-line inotropic drug (dopamine vs cardiovascular support (7). Our results showed that although patients who received epinephrine started with a higher VIS due to a factor equivalence between drugs, 49% of patients on dopamine group presented with a VIS score (nonsignificant) above 25 in the first 24 hours due to the greater need for other vasoactive drugs because most of them (52%) did not respond to this drug. Therefore, the VIS score applied to this population expresses the use of other catecholamine rather than dopamine. We definitely agree with a possible imbalance between dose regimens. However, we decided to test the doses proposed by guidelines. They suggest the initiation of dopamine of 5 to 10 μg/kg/min and afterward switch to epinephrine (0.05–0.3 μg/ kg/min) if there is no response to dopamine (8). We focused on doses that could be safely delivered by a peripheral or intraosseous line and on theoretically inotropic doses. Our findings may not allow us to conclude that definitely epinephrine was superior to dopamine, but we could say that dopamine in the tested dose range may not be effective as firstline drug for children with septic shock. The author has disclosed that she does not have any potential conflicts of interest.