Geneva Statement on Heritable Human Genome Editing: The Need for Course Correction.

As public interest advocates, policy experts, bioethicists, and scientists, we call for a course correction in public discussions about heritable human genome editing. Clarifying misrepresentations, centering societal consequences and concerns, and fostering public empowerment will support robust, global public engagement and meaningful deliberation about altering the genes of future generations.

Return and Disclosure of Research Results: Parental Attitudes and Needs Over Time in Pediatric Oncology.

OBJECTIVES: To explore parental attitudes regarding the return and disclosure of research findings in pediatric cancer trials over time. STUDY DESIGN: Two surveys were set up to evaluate the stability of parental attitudes. One survey was carried out among 581 parents whose child was diagnosed recently (response rate, 53.5%). A second, population-based survey was set up with a time interval of 4 years between first cancer diagnosis and survey in which 1465 parents were included (response rate, 55.1%). RESULTS: Almost all surveyed parents stated a parental right to receive aggregate research results. Fifty-five percent of the parents who recently participated in trials and 62% of those asked after a multiyear time interval thought that disclosure of individual findings is in any case necessary (P = .0034). The respondents wanted to restrict the duty to disclose study results to the child according to their notion of the child's well-being, composed of child's maturity, impairment of the parent-child relationship, and the quality of the results. CONCLUSIONS: Attitudes of parents regarding the return of research findings change over time. Shortly after diagnosis, parents are mainly interested in aggregate findings. Interest in individual findings appeared to increase as more time elapsed between cancer diagnosis and survey.

Informed consent, biobank research, and locality: perceptions of breast cancer patients in three European countries.

Comparative studies are missing that explore how socio-cultural and institutional circumstances influence patient comprehension and expectations regarding informed consent for current and future research on their tissue and data. This study compares how breast cancer patients in three European countries (the United Kingdom, Belgium, and Germany) who have consented to participate in tumor banking assess the given consent and the accompanying local contextual factors influencing it. Our survey demonstrates that only 59% of the patients in the British survey, but about 90% in the German and Belgian surveys, correctly recalled tissue and data donation for study purposes. Of those who remembered the study participation status correctly, about 90% had altruistic motives. At the same time, approximately half of the survey participants, or even 70% of the Belgians, expected personal benefit from research participation and information on cancer risk within the family. About half of the interviewees, but only 27% of the British participants, definitively wanted to be asked for re-consent for future research. Of the local contextual factors under study, participants' appraisals of medical science and data protection were particularly pertinent. More culturally and contextually sensitive comparative research is needed to better understand patient attitudes toward research participation and tissue donation in the context of biobank research.

Parental informed consent in pediatric cancer trials: a population-based survey in Germany.

BACKGROUND: Ensuring adequate parental consent is a key issue of ethical practice in pediatric oncology. In Germany, however, knowledge about parental comprehension and satisfaction with the informed consent procedure is limited, and representative data on parents' perspectives are still missing. Based on data collected by means of a population-based survey, we evaluated the parental recall of the informed consent process for pediatric clinical trials, and how they rated the consent process retrospectively. PROCEDURE: A standardized survey was carried out among 1,465 parents whose children were first diagnosed in 2005 with a disease defined by ICCC-3 in the German Childhood Cancer Registry (response: 55.1%). The survey's primary objective was to assess how well parents were able to recall of the informed consent process. To evaluate the results, we set up a second survey among 581 parents who had given consent recently for their child's participation in a clinical trial (response: 53.5%). RESULTS: Approximately 81% of the parents in the population-based survey correctly remembered whether or not their child had been enrolled in a clinical trial or treated off-trial. The ability to recall accurately is significantly lower if the parents have a migration background or if their child was not a trial participant. However, parents who recalled the child's trial participation status incorrectly felt as adequately informed as parents who recalled it correctly. CONCLUSIONS: Our results identified weak points and vulnerable subgroups in the parental consent process in pediatric oncology in Germany.

[Individualisation of medicine: medical philosophy and societal implications of an ambiguous guiding principle]. / Individualisierung der Medizin: medizintheoretische und gesellschaftliche Implikationen eines mehrdeutigen Leitbilds.

Based on genetic or other biomarkers, increasingly good predictions of individual disease dispositions and drug reactions as well as the characteristics of tumours and their response to treatment can be produced. Hopefully, preventive or therapeutic interventions may thus be better adapted to the individual's physical endowments to increase treatment efficiency and reduce unwanted drug reactions. These developments have been summarised under the conceptual umbrella of "individualised" or "personalised medicine". In contrast to early expectations, clinical implementation of individualised medicine proceeds rather slowly. At the same time important philosophical and social issues emerge. This article will start by introducing some areas of applications of individualised medicine. In a second step, the guiding principle of "individualisation" of treatment and its ambiguity will be reflected. The third part discusses some of the philosophical and social implications of these developments. The article ends with a conclusion and some suggestions for further research.

Disclosure of individual research results in clinico-genomic trials: challenges, classification and criteria for decision-making.

While an ethical obligation to report findings of clinical research to trial participants is increasingly recognised, the academic debate is often vague about what kinds of data should be fed back and how such a process should be organised. In this article, we present a classification of different actors, processes and data involved in the feedback of research results pertaining to an individual. In a second step, we reflect on circumstances requiring further ethical consideration. In regard to a concrete research setting--the one of clinico-genomic research--we discuss what kinds of difficulties have to be faced when returning individual research results to trial participants. In a last step, we elaborate on a stepwise model to trigger the individual feedback process. Hence, this paper gives guidance on how to feedback individual research results in a specific research setting and responds at the same time to new challenges in the debate on the duty to return individual research findings.

Pharmacogenetics, adverse drug reactions and public health.

Adverse drug reactions (ADRs) are a major public health problem. Pharmacogenetic testing prior to drug treatment is supposed to considerably alleviate this problem. The state of pharmacogenetic development was assessed by a systematic literature review, supplemented by expert interviews. Analysis of three case examples revealed that - with the exception of thiopurine methyltransferase (TPMT) - studies are lacking which unambiguously prove the clinical value of pharmacogenetic testing. Testing can prevent some, but by far not all ADRs. Since it does not compensate for clinical monitoring, pharmacogenetics can be regarded as add-on technology, applied in addition to established methods. A non-representative, explorative survey conducted amongst members of the German Society of Laboratory Medicine revealed that the demand for testing is limited and has not increased much, although a certain increase is expected in the future.

Individualized pharmacogenetic therapy: a critical analysis.

OBJECTIVE: Individualized, or personalized, therapy is highlighted as the declared goal of pharmacogenetics. In this paper, the content and significance of the individualization concept are analyzed. METHOD: Our analysis is based on a systematic reading of the current literature pertinent to pharmacogenetics. RESULTS: This analysis reveals that the pharmacogenetic understanding of individualization is based on a biomechanistic paradigm. In contrast to a notion of individualized therapy based on a biopsychosocial paradigm, this biomechanistic concept does not provide for individualization in psychosocial terms, but instead leads to the stratification and classification of patient populations. This finding does not necessarily cast doubt on the efficacy of pharmacogenetics, but does call its underlying ideology into question. CONCLUSION: The term 'individualization of therapy' does not reflect the real potential of pharmacogenetics, but instead represents a widely used and theoretically unjustified publicity slogan.

Prospects and limits of pharmacogenetics: the thiopurine methyl transferase (TPMT) experience.

Thiopurine drug metabolism is a quintessential case of pharmacogenetics. A wealth of experimental and clinical data on polymorphisms in the thiopurine metabolizing enzyme thiopurine methyl transferase (TPMT) has been generated in the past decade. Pharmacogenetic testing prior to thiopurine treatment is already being practiced to some extent in the clinical context, and it is likely that it will be among the first pharmacogenetic tests applied on a regular basis. We analyzed the published TPMT data and identified some lessons to be learned for the future implementation of pharmacogenetics for thiopurines as well as in other fields. These include the need for comprehensive and unbiased data on allele frequencies relevant to a broad range of populations worldwide. The nature and frequency of TPMT gene polymorphisms in some ethnic groups is still a matter of speculation, as the vast majority of studies on TPMT allele distribution are limited to only a small subset of alleles and populations. Secondly, an appreciation of the limits of pharmacogenetics is warranted, as pharmacogenetic testing can help in avoiding some, but by far not all adverse effects of drug therapy. An analysis of six clinical studies correlating adverse thiopurine effects and TPMT genotype revealed that an average of 78% of adverse drug reactions were not associated with TPMT polymorphisms. Pharmacogenetic testing will thus not eliminate the need for careful clinical monitoring of adverse drug reactions. Finally, a careful approach toward dose increases for patients with high enzyme activity is necessary, as TPMT-mediated methylation of thiopurines generates a possibly hepatotoxic byproduct.

[Evaluation of genetic screening. The problem of hidden value judgements, conceptual arbitrary attitudes and methodological leeway in the so-called screening process]. / Die Bewertung Genetischer Screenings. Zum Problem versteckter Werturteile, konzeptueller Beliebigkeit und methodischer Spielräume in sogenannten Screening-Ratios.

Population-wide genetic screenings can multiply benefits, but may also increase risks and other adverse effects of genetic testing. Insofar, there is a particular need for legitimization of genetic screenings. Health economic calculus and the so-called "screening ratios" aim to relate information about potential costs to potential benefits. Their implicit claim of being rational, however, can only be realised partially, since each concept is based on a number of value judgements allowing for different decisions, which can be a critical outcome factor. All the more so, since different players use different ratios. Against this background, disclosure of normative foundations and perspectives in cost-benefit ratios of genetic screenings seems to be imperative.