Jan Piasecki

Child's assent in research: Age threshold or personalisation?

BackgroundAssent is an important ethical and legal requirement of paediatric research. Unfortunately, there are significant differences between the guidelines on the details of assent.DiscussionWhat often remains unclear is the scope of the assent, the procedure for acquiring it, and the way in which children’s capacity to assent is determined. There is a general growing tendency that suggests that the process of assent should be personalised, that is, tailored to a particular child. This article supports the idea of personalisation. However, we also propose placing limits on personalisation by introducing a suggested requirement of assent starting at a school-age threshold. In some situations RECs/IRBs and researchers could reduce the suggested threshold.SummaryA recommended age threshold is likely to serve the interests of children better than ambiguous and flexible criteria for personalised age determination.

Non-beneficial pediatric research: individual and social interests

Biomedical research involving human subjects is an arena of conflicts of interests. One of the most important conflicts is between interests of participants and interests of future patients. Legal regulations and ethical guidelines are instruments designed to help find a fair balance between risks and burdens taken by research subjects and development of knowledge and new treatment. There is an universally accepted ethical principle, which states that it is not ethically allowed to sacrifice individual interests for the sake of society and science. This is the principle of precedence of individual. But there is a problem with how to interpret the principle of precedence of individual in the context of research without prospect of future benefit involving children. There are proposals trying to reconcile non-beneficial research involving children with the concept of the best interests. We assert that this reconciliation is flawed and propose an interpretation of the principle of precedence of individual as follows: not all, but only the most important interests of participants, must be guaranteed; this principle should be interpreted as the secure participant standard. In consequence, the issue of permissible risk ceiling becomes ethically crucial in research with incompetent subjects.

What Do Ethical Guidelines for Epidemiology Say About an Ethics Review? A Qualitative Systematic Review

Epidemiological research is subject to an ethics review. The aim of this qualitative review is to compare existing ethical guidelines in English for epidemiological research and public health practice in regard to the scope and matter of an ethics review. Authors systematically searched PubMed, Google Scholar and Google Search for ethical guidelines. Qualitative analysis (constant comparative method) was applied to categorize important aspects of the an ethics review process. Eight ethical guidelines in English for epidemiological research were retrieved. Five main categories that are relevant to the review of epidemiological research by Institutional Review Boards/Research Ethics Committees were distinguished. Within the scope of main categories, fifty-nine subcategories were analyzed. There are important differences between the guidelines in terms of the scope and matter of an ethics review. Not all guidelines encompass all identified ethically important issues, and some do not define precisely the scope and matter of an ethics review, leaving much to the ethics of the individual researchers and the discretion of IRBs/RECs.

Child's objection to non-beneficial research: capacity and distress based models.

A child’s objection, refusal and dissent regarding participation in non-beneficial biomedical research must be respected, even when the parents or legal representatives have given their permission. There is, however, no consensus on the definition and criteria of a meaningful and valid child’s objection. The aim of this article is to clarify this issue. In the first part we describe the problems of a child’s assent in research. In the second part we distinguish and analyze two models of a child’s objection to research: the capacity-based model and the distress-based model. In the last part we present arguments for a broader and unified understanding of a child’s objection within regulations and practices. This will strengthen children’s rights and facilitate the entire process of assessment of research protocols.

Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic review with meta-analysis

Background Pediatric Phase I cancer trials are critical for establishing the safety and dosing of anti-cancer treatments in children. Their implementation, however, must contend with the rarity of many pediatric cancers and limits on allowable risk in minors. The aim of this study is to describe the risk and benefit for pediatric cancer Phase I trials. Methods and findings Our protocol was prospectively registered in PROSPERO (CRD42015015961). We systematically searched Embase and PubMed for solid and hematological malignancy Phase I pediatric trials published between 1 January 2004 and 1 March 2015. We included pediatric cancer Phase I studies, defined as “small sample size, non‑randomized, dose escalation studies that defined the recommended dose for subsequent study of a new drug in each schedule tested.” We measured risk using grade 3, 4, and 5 (fatal) drug-related adverse events (AEs) and benefit using objective response rates. When possible, data were meta-analyzed. We identified 170 studies meeting our eligibility criteria, accounting for 4,604 patients. The pooled overall objective response rate was 10.29% (95% CI 8.33% to 12.25%), and was lower in solid tumors, 3.17% (95% CI 2.62% to 3.72%), compared with hematological malignancies, 27.90% (95% CI 20.53% to 35.27%); p < 0.001. The overall fatal (grade 5) AE rate was 2.09% (95% CI 1.45% to 2.72%). Across the 4,604 evaluated patients, there were 4,675 grade 3 and 4 drug-related AEs, with an average grade 3/4 AE rate per person equal to 1.32. Our study had the following limitations: trials included in our review were heterogeneous (to minimize heterogeneity, we separated types of therapy and cancer types), and we relied on published data only and encountered challenges with the quality of reporting. Conclusions Our meta-analysis suggests that, on the whole, AE and response rates in pediatric Phase I trials are similar to those in adult Phase I trials. Our findings provide an empirical basis for the refinement and review of pediatric Phase I trials, and for communication about their risk and benefit.

Relevant Information and Informed Consent in Research: In Defense of the Subjective Standard of Disclosure

In this article, we seek to contribute to the debate on the requirement of disclosure in the context of informed consent for research. We defend the subjective standard of disclosure and describe ways to implement this standard in research practice. We claim that the researcher should make an effort to find out what kinds of information are likely to be relevant for those consenting to research. This invites researchers to take empirical survey information seriously, attempt to understand the cultural context, talk to patients to be better able to understand what can be potentially different concerns and interests prevalent in the target population. The subjective standard of disclosure should be seen as a moral ideal that perhaps can never be perfectly implemented but still can and should be used as a normative ideal guiding research practice. In the light of these discussions, we call for more empirical research on what considerations are likely to be perceived as relevant by potential research participants recruited from different socio-economic and cultural groups.

Forensic uses of research biobanks: should donors be informed?

Occasional reports in the literature suggest that biological samples collected and stored for scientific research are sometimes accessed and used for a variety of forensic purposes. However, donors are almost never informed about this possibility. In this paper we argue that the possibility of forensic access may constitute a relevant consideration at least to some potential research subjects in deciding whether to participate in research. We make the suggestion that if some type of forensic access to research collections is likely to be perceived by the subjects as a reason against donating their biological materials, there are good ethical reasons to make this type of access impossible or at least severely restricted. We also provide an ethical argument for the claim that, if a total ban on this type of forensic access cannot be achieved, potential research subjects should be informed about the extent to which this type of forensic access is possible.

Erasmus Mundus Master of Bioethics: a case for an effective model for international bioethics education

Designing bioethics curriculum for international postgraduate students is a challenging task. There are at least two main questions, which have to be resolved in advance: (1) what is a purpose of a particular teaching program and (2) how to respectfully arrange a classroom for students coming from different cultural and professional backgrounds. In our paper we analyze the case of the Erasmus Mundus Master of Bioethics program and provide recommendations for international bioethics education. In our opinion teaching bioethics to postgraduate international students goes beyond curriculum. It means that such a program requires not only well-defined goals, including equipping students with necessary skills and knowledge, but also it should first and foremost facilitate positive group dynamics among students and enables them to engage in dialogue to learn from one another.

Google Search as an Additional Source in Systematic Reviews

Marko Curkovic in his letter (2017) points out that using Google Search in our systematic review (Piasecki et al. 2017) could have led to the so-called “bubble effect”, a form of selection bias. We take seriously this concern. Google Search is indeed an imperfect tool to perform systematic reviews: the search algorithm is not known and cannot be controlled, Google adapts the search to each user in order to personalize information and, as a result, a systematic search is quite probably not replicable. To avoid problems related to a personalized search, the primary source of the data in our study was a systematic search in PubMed. Searches in Google Scholar and Google Search were considered to be additional sources only. We expected that the total number of documents will be low, and we were rather more concerned with the comprehensiveness of our search than its representativeness, having in mind the qualitative, not the statistical character of the study. Moreover, in order to avoid personalization of search results, we logged off from all Google accounts. We regret that we did not describe this step in our paper. As a result, Google Search allowed to identify three additional guidelines. Google Scholar and Google Search are considered to be important sources of grey literature, governmental and institutional reports (Haddaway et al. 2015; Hagstrom et al. 2015). In performing our study, we assumed that not all the guidelines

Assent in Paediatric Research and Its Consequences

This article proposes a consequentialist approach to the problem of children’s assent in research. To date, one of the main controversies concerning assent has been about the necessary conditions for making a morally significant decision. Some argue that to make a morally significant decision a child has to understand the abstract concept of altruism. Therefore it is crucial to determine at what stage of development this ability arises. Others argue that the crucial condition is to determine when children gain the capacities for making autonomous decisions regarding participation in research. Since these philosophical and psychological controversies are quite persistent, a calculation of the benefits and harms might be essential for implementing a uniform policy. We argue that the benefits of a properly applied policy requiring assent from all capable children is more beneficial than a policy setting a high age threshold for assent. We also suggest that the consequentialist argument depends on empirical premises that might be either supported or proven false by empirical research.