Hannes Kahrass

Introduction: Health technology assessment (HTA) reports are written for healthcare decision makers, particularly in relation to reimbursement/pricing, and are intended to assess clinical effectiveness, safety, and cost. Four additional domains are further considered in what is called a “full HTA”: ethical, legal, social, and organizational aspects. The ethical aspects have long been the subject of debate regarding how they should be processed. It would be important if the following questions could be answered: Who publishes full HTA reports and how? Which methods are used in the ethics domain? What kind of results do they produce? However, such a “mapping of the field” turns out to be difficult. Despite the existence of international HTA registers, we were not able to compile a comprehensive sample of full HTA reports. Therefore, the aim of our study was rather to explore a) substantially: Which information can be expected to be (easily) found, which can only be obtained with considerable effort, and which remain (for the time being) in the dark? And b) methodologically: Is it possible to do meaningful meta-research in this field? Methods and results: In the attempt to explore the possibilities of meta-research, we were able to track down and analyze thirty-nine full HTA reports from six countries. Conclusions: While not representative of the whole field, this analysis shows the possibilities and challenges to meta-research, but nonetheless also provides some substantial insight into the characteristics of such reports, with a particular focus on the methods used to process ethical aspects.

Can nonhuman animals be used for the benefit of humans in a scientifically and morally justified manner and, if yes, how? Based on our own experiences as scholars from various academic backgrounds, we argue that this question can only be answered as an interdisciplinary and international endeavor, considering insights from research ethics and animal ethics as well as scientific and legal aspects. The aim of this article is to contribute to the foundation of the emerging field of animal research ethics. In doing so, we describe the following seven phases of animal research experiments: ethical, legal and social presumptions (phase 0), planning (phase I), review (phase II), conduct of experiments (phase III), publication/dissemination (phase IV), further exploitation of results (phase V), and evaluation (phase VI). In total, 20 key ethical, legal, and practical challenges that an ethical framework for the use of animals in research needs to address are identified and analyzed. Finally, we characterize the following four meta-challenges and opportunities associated with animal research ethics as a field: (1) moral pluralism, (2) the integration of views and positions outside the laboratory, (3) international plurality of conduct, standards, and legal norms, and (4) interdisciplinary education.

Background: Research model selection decisions in basic and preclinical biomedical research have not yet been the subject of an ethical investigation. Therefore, this paper aims, (1) to identify a spectrum of reasons for choosing between animal and alternative research models (e.g., based on in vitro or in silico models) and (2) provides an ethical analysis of the selected reasons. Methods: In total, 13 researchers were interviewed; the interviews were analyzed qualitatively. The ethical analysis was based on the principlism approach and a value judgement model. Results: This paper presents 66 reasons underlying the choice of researchers using animal (27 reasons) or alternative models (39). Most of the reasons were assigned to the work environment (29) and scientific standards (22). Other reasons were assigned to personal attitudes (11) and animal welfare (4). Qualitative relevant normative differences are presented in the ethical analysis. Even if few reasons can be rejected outright from an ethical point of view, there are good reasons to give some more weight than others. Conclusions: The spectrum of reasons and their ethical assessment provide a framework for reflection for researchers who may have to choose between animal models and (investing in) alternatives. This can help to reflect on and ethically justify decisions.

Background: Little is known about the decisional background of choosing an appropriate disease model. Therefore, this paper aims, (1) to identify a spectrum of reasons for choosing between animal and non-animal disease models and (2) provides an ethical analysis of these reasons. Methods: 13 researchers from basic and preclinical research were interviewed, the interviews were analyzed qualitatively and the results were categorized. The ethical analysis was based on the principlism approach and a value judgement model. Results: This paper presents 66 reasons why researchers use animal (41 %) or alternative, non-animal disease models (59 %). Most of the reasons were be assigned to the work environment (29 reasons) and scientific standards (22 reasons). Other reasons were assigned to personal attitudes (11 reasons) and animal welfare (4 reasons). Qualitative relevant normative differences are presented in the ethical analysis. Even if few reasons can be rejected outright from an ethical point of view, there are good reasons to give some more weight than others. Conclusions: The spectrum of reasons and its ethical assessment provide a framework for reflection for researchers who may have to choose between animal models and (investing in) alternatives. This can help to reflect on and justify decisions.

Background Systematic reviews (SR) are well elaborated and established for synthesizing statistical information, for example of clinical studies, for determining whether a clinical intervention is effective. SRs are also becoming more and more popular in bioethics. However, the established approach of conducting and reporting cannot be transferred to SRs on ethically sensible questions directly. This is because the object of investigation is not statistical information, but conceptual or normative information, e.g. ethical norms, principles, arguments or conclusions. There is evidence that the quality of reporting of SRs on ethics literature could be improved in many regards. Although insufficient reporting is not a problem specific to bioethics, as poorly reported manuscripts are also very common in SRs in e.g. medicine, authors of such SRs have the possibility to follow existing reporting guidelines (e.g. PRISMA). Method An international group of authors with years of experience in conducting and reviewing SRs on ethics literature developed a reporting guideline for this specific area of application (RESERVE). The relevant background was provided by two reporting guidelines: PRISMA for systematic reviews and ENTREQ due to the importance of qualitative research approaches. Results RESERVE has 22 items and is intended to provide authors of SRs on ethics literature with all information necessary for an adequate reporting. It also allows readers, reviewers and journal editors critically evaluating the presented results and conclusions made. In this paper, we explain the rationale and give examples for each item. Conclusions While we acknowledge heterogeneity on how to conduct a SR on ethics literature, we still maintain that there is a need for general reporting standards for improving transparency, understandability and verifiability. We invite authors of SRs on ethics literature to test and evaluate the usefulness of RESERVE. We hope for a critical discussion of the guideline and welcome its broad implementation.

Systematic reviews (SR) are very well elaborated and established for synthesizing statistical information, for example of clinical studies, for determining whether a clinical intervention is effective. SRs are also becoming more and more popular in bioethics. However, the established approach of conducting and reporting a SR cannot be transferred to corresponding work on ethically sensible questions directly. This is because the object of investigation is not statistical information, but conceptual or normative information, e.g., ethical norms, principles, arguments or conclusions. There is some evidence that the quality of reporting of SRs on ethics literature could be improved in many regards. Although insufficient reporting is not a problem specific to bioethics, as poor study reports are also very common in SRs in e.g. medicine, authors of such SRs have the possibility to follow a reporting guideline – the well-established statement on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). For SRs on ethics literature, the PRISMA Statement can only be partially adopted due to the different type of information searched and analyzed.Thus, an international group of authors with years of experience in conducting and reviewing SRs on ethics literature adapted PRISMA for its application in the field of bioethics (“PRISMA-Ethics”). As methods stemming from qualitative research are often used for analysis and synthesis in SRs on ethics literature, also elements of the ENTREQ Guideline were incorporated in PRISMA-Ethics. The resulting reporting guideline has 22 items and is intended to provide authors of SRs on ethics literature with all information necessary for an adequate reporting of their SRs. It also allows readers, reviewers and journal editors critically evaluating the presented results and conclusions made. In this paper, we explain the rationale and give examples for each item. While we acknowledge heterogeneity on how to conduct a SR on ethics literature, we still maintain that there is a need for general reporting standards for improving transparency, understandability and verifiability of such SRs. We invite authors of SRs on ethics literature to test PRISMA-Ethics and to evaluate its usefulness. We hope for a critical discussion of the guideline and welcome its broad implementation.

Objective Timely publication of clinical trial results is central for evidence-based medicine. The performance of university medical centers (UMCs) regarding timely results publication informs the local and national decision makers, patients, and the public about the need to improve trial results dissemination. Study Design and Setting Following the same search and tracking methods used in our previous study for the years 2009 - 2013, we identified trials led by German UMCs completed between 2014 and 2017 and tracked results dissemination for the identified trials. Results We identified 1,658 trials in the 2014-2017 cohort. Of these trials, 43% published results as either journal publication or summary results within 24 months after completion date, which is an improvement of 3.8% percentage points compared to the previous study. At the UMC level, the 24-month publication rates varied from 14% to 71%. Five years after completion, still 30% of the trials remained unpublished. Conclusion Despite minor improvements compared to the previously investigated cohort, the rate of timely reporting of trials led by German UMCs remains low. German UMCs should take further steps to improve timely reporting rates.

Background: Informed consent documents for clinical studies should disclose all reasonably foreseeable risks and benefits. Little guidance exists on how to navigate the complexities of risk–benefit communication, especially in early clinical research. Practice-oriented development of such guidance should be informed by evidence on what and how details of risks and benefits are currently communicated. Method: We surveyed the responsible parties of phase I/II trials registered in ClinicalTrials.gov that started 2007 or later and completed between 2012 and 2016 to sample informed consent documents from a broad spectrum of early phase clinical trials. Based on an assessment matrix, we qualitatively and quantitatively assessed the informed consent documents for details of risk–benefit communication. Results: The risk–benefit communication in the 172 informed consent documents differed substantially in several regards. The outcome, extent, and likelihood of health risks, for example, were described in 83%, 32%, and 63% of the informed consent documents. Only 45% of informed consent documents specified the outcome of mentioned health benefits, and the extent and likelihood of health benefits were never specified. From those informed consent documents reporting risk likelihoods, only 57% added frequency numbers to words such as “common” or “rare,” and even in these cases, we found strong variations for presented frequency ranges. Substantial heterogeneity also exists for how informed consent documents communicate other risk and benefit types and related safeguards. Conclusion: Our study points to several shortcomings and heterogeneities in how informed consent documents communicate risks and benefits to potential research participants. Health risks, for example, should be specified with frequency numbers, and health benefits should be specified at least by mentioning their outcomes. Further demand for research and policy development is needed to harmonize risk–benefit communication and to clarify ways to specify the likelihood of health benefits.