Christiane Druml

The European Union Directive on Clinical Research: present status of implementation in EU member states’ legislations with regard to the incompetent patient

A new law or an amendment to existing law has already been incorporated in national statutes or is in the process of approval in The Netherlands, France, Belgium, Italy, Denmark, Germany, Austria, and Spain (Table 1). In other countries discussions and proposals are still not complete. In some countries the proposals are limited to drug research (as was intended by the Directive); in others (Belgium, France, The Netherlands, the United Kingdom) its scope has been broadened to include all types of research (epidemiology, genetics, pathophysiology, and observational studies).

The European Union Directive and the protection of incapacitated subjects in research: an ethical analysis

ObjectiveWe perform an ethical analysis of European Union Directive 2001/20/EC on the simplification and harmonization of guidelines regarding good clinical practice in the conduct of clinical trials involving drugs.BackgroundThe Directive provides guidance on protecting incapacitated subjects who participate in drug clinical trials. Such guidance promotes society’s obligations of beneficence because the participation of incapacitated subjects in research is crucial in advancing the understanding and treatment of serious diseases. The Directive requires proxy consent for incapacitated subjects which adheres to the principle of respect for persons. The Directive also recommends additional safeguards to further protect subjects against exploitation and harm. These include respect for the assent and dissent of incapacitated subjects and the “necessity” and “subject-condition” requirements.ResultsWhile these essential protection mechanisms are commendable, the Directive fails to endorse other safeguards that have been recommended by other research ethics guidelines, especially for riskier research. The Directive’s silence regarding research in the emergency setting frustrates the principle of beneficence because the lack of guidance might prove to be a barrier for the conduct of such potentially beneficial research.ConclusionsWe conclude that the European Directive fails in many respects to promote several important ethical principles in research involving incapacitated subjects.

Informed consent of incapable (ICU) patients in Europe: existing laws and the EU Directive.

Purpose of the reviewThe new European legislation on good clinical practice in the conduct of clinical trials on drugs has raised serious concern that potentially lifesaving studies cannot be carried out in critically ill patients in Europe anymore after May 2004. The requirement of nominating a legal representative for obtaining informed consent before inclusion will deprive current and future patients of participation in research. The new legislation does not differentiate between patients who are incompetent because of a psychiatric illness or dementia and patients who are incapacitated owing to an emergency situation. All those patients may be enrolled in a clinical trial only after informed consent has been granted by a legal representative. Relevant findingsRecent publications regarding the new European legislation manifest an outcry by intensive care specialists, emergency medicine specialists, traumatologists, and specialists of other related disciplines concerned about the proposed active withholding of potentially beneficial therapies for this very unfortunate group of patients. Many authors, although acknowledging the ethical principle of autonomy, express that in the field of emergency medicine not all criteria of autonomy may be met. The Declaration of Helsinki requires that even the best prophylactic, diagnostic, and therapeutic methods must continuously be challenged through research. There is agreement among the authors that critically ill patients should not be deprived from the benefits of research. SummaryMany groundbreaking therapies will not be scientifically evaluated anymore, and thus beneficial treatments in fatal diseases will be prevented. The European legislation is asked to adapt the Directive to promote research in critically ill patients.

Research ethics committees in Europe: trials and tribulations

IntroductionEthics committees have been an integral part of clinical research since 1975, when they were introduced through the amendment of the Declaration of Helsinki. Every proposal for clinical research on human subjects has to be submitted to an independent ethics committee for review and approval. The European Clinical Trials Directive 2001/20/EC was implemented in 2004 to harmonise the legislative framework for clinical research in Europe in order to make Europe more competitive in clinical research while at the same time improving the protection of research participants.ResultsWe have evaluated the situation of ethics committees in Europe five years after the implementation of the new law with special consideration of the number of Ethics Committees per European Member State and the number of members within the specific committees, including the selection of members, also in regard to gender aspects and training requirements, the remuneration or compensation of members in regard of their review obligations, and also issues of conflicts of interest.ConclusionInadequate remuneration for professional services and gender imbalance are universal concerns across Europe. As the position of ethics committees changes continuously towards greater responsibility, further guidance is needed to uniformly adapt their structures to those needs.

Gender aspects in medical publication - the Wiener klinische Wochenschrift.

ZusammenfassungFRAGESTELLUNG UND ZIEL: Medizin ist ein akademischer Fachbereich, in dem nach wie vor ein Ungleichgewicht zwischen Männern und Frauen herrscht. Weltweit sind mehr als die Hälfte aller Medizinstudenten weiblich, jedoch erreicht nur ein kleiner Prozentsatz später eine Führungsposition. Das Ziel der vorliegenden Arbeit war es, zu analysieren, wie diese Situation in einer allgemein-medizinisch-wissenschaftlichen Fachzeitschrift reflektiert wird. METHODIK: Alle Manuskripte, die in dem Zeitraum zwischen Jänner 2001 und September 2009 bei der Wiener klinischen Wochenschrift zur Publikation eingereicht waren, wurden in die Untersuchung einbezogen. Folgende Gesichtspunkte wurden analysiert: Erstautorenschaft von Frauen in Bezug auf eingereichte sowie angenommene Manuskripte, eingeladene Manuskripte, Art der Publikation, medizinisches Fachgebiet der Manuskripte, Prozentsatz an eingeladenen Gutachtern und Qualität der Gutachten. ERGEBNISSE: Im Beobachtungszeitraum wurden 2507 Manuskripte bei der Wiener klinischen Wochenschrift zur Publikation eingereicht, davon hatten 26% weibliche Erstautoren. Dieser Prozentsatz stieg kontinuierlich von 16% in 2001 bis auf 32% in 2007 an und blieb in der Folge konstant. Der Anteil an Arbeiten, die von Frauen zur Publikation eingereicht waren, war abhängig vom medizinischen Sonderfach – so betrug er 48% bei pädiatrischen Manuskripten, aber nur 12% bei kardiologischen Arbeiten. Der Anteil an zur Publikation angenommenen Arbeiten war bei männlichen und weiblichen Erstautoren gleich. Es gab jedoch einen größeren Anteil von sofort abgelehnten Manuskripten mit einer weiblichen Erstautorin als mit einem männlichen Erstautor (21% versus 16%). Manuskripte mit einer weiblichen Erstautorin nannten häufiger einen anderen korrespondierenden Autor als Manuskripte mit einem männlichen Erstautor. Mehr als 40% aller eingereichten Originalarbeiten, 24% der Übersichten, aber nur 10% der Editorials wiesen eine Frau als Autorin auf. Während der letzten 5 Jahre waren nur 11% der Gutachter Frauen, die Qualität der Gutachten war aber generell höher. Unter den 21 Mitgliedern des Editorial Boards ist nur eine einzige Frau. ZUSAMMENFASSUNG: Zwischen 2001 und 2007 stieg der Anteil an Manuskripten, die von Frauen eingereicht wurden, konstant an und beträgt derzeit ca. 30%, in einzelnen Fachbereichen wie Kinderheilkunde bis zu 50%. Nichtsdestotrotz liegt nach wie vor eine massive Ungleichstellung zwischen männlichen und weiblichen Autoren vor: Übersichtsarbeiten sowie eingeladene Editorials sind selten von Frauen verfasst, ein sehr niedriger Anteil an Manuskripten wird von Frauen begutachtet, wobei von Frauen erstellte Gutachten meist bessersind. Nur ein Mitglied des Editorial Board ist eine Frau. Dies widerspiegelt die generelle Situation in der akademischen Medizin. Medizinisch-wissenschaftliche Zeitschriften müssen aktiv dazu beitragen, diese Ungleichheiten zu beseitigen.SummaryOBJECTIVE: Medicine is a discipline where there are still pronounced gender imbalances. Whereas worldwide about 50% of beginners in medical schools are female, only few of them reach leading positions. Our aim was to analyze how this situation is reflected in a peer-reviewed general medical-scientific journal. METHODS: We screened all papers submitted to the Wiener klinische Wochenschrift – The Middle European Journal of Medicine between January 2001 and September 2009, analyzing the percentage of female first authors of submitted papers and accepted papers, the contribution of female authors depending on the type of article and medical specialty, and the percentage of invited female peer reviewers as well as the quality of their reviews. MAJOR RESULTS: During the period studied, a total of 2507 manuscripts were submitted to Wiener klinische Wochenschrift. 26% of these papers had female first authors, and this proportion increased continuously from 16% in 2001 to 32% in 2007, whereafter it remained constant. The proportion of papers submitted by female first authors was dependent on the medical subspecialty (e.g. 48% female first authors of pediatric papers, 12% female first authors of cardiology papers). There was no difference in the acceptance rate of papers by male and female first authors; however, a somewhat higher rate of papers with female first authors was subject to rapid rejection (21% vs. 16%). Papers with female first authors more often named a different corresponding author than papers with male first authors, and in most of these cases the corresponding author was a man. More than 40% of all submitted original papers, 24% of the review articles, but only 10% of the editorials had female first authors. During the years studied only 5–11% of reviewers were women, despite that the quality of their reviews was generally better than those by men. Among the 21 members of the editorial board only one is a woman. CONCLUSION: Between 2001 and 2007 the percentage of manuscripts submitted to Wiener klinische Wochenschrift by female authors constantly increased and is now around 30%, reaching almost 50% in some specialties such as pediatrics. Nevertheless, there remains a massive gender imbalance in Wiener klinische Wochenschrift: review papers or invited editorials are only rarely authored by female researchers, a very low percentage of peer reviewers is female – although the quality of their reviews is generally better – and only one member of the editorial board is female. Even though this is mostly a reflection of the general situation in academic medicine, medical journals can and must take action and contribute to the elimination of these gender inequalities.

Protocols in expedited review: tackling the workload of ethics committees

PurposeThis paper describes the experience of the Ethics Committee of the Medical University of Vienna, Austria, while managing the workload of clinical study applications.MethodsAn expedited review process was introduced for initial review of study protocols regarded as minimal risk interventions in March 2004.ResultsA total of 504 study protocols were submitted for review in 2003 and this number has increased to 743 in 2007. Two hundred sixty eight studies were classified as minimal risk in 2007 and allocated to a subgroup of the Committee for review. The time to full approval was shorter for these studies as compared to other protocols.ConclusionsImplementation of initial expedited review can improve the performance of an Ethics Committee. A framework to achieve a single opinion for multisite research of minimal risk interventions should be considered to facilitate these low risk studies.

Stem Cell Research: Toward Greater Unity in Europe?

There are four major positions on human embryonic stem cell research in the different member states of the European Union, ranging from permissive to very restrictive. This reflects the diversity of research systems within Europe and poses a challenge to developing a common European research policy.

Multicentre clinical trials

Sir—C Cornu and colleagues (Jan 2, p 6 3 ) describe the difficulties and administrative hurdles of implementing a multicentre clinical trial in Europe. We fully agree that implementation of such trials is probably the utmost priority in European clinical research. An inappropriately small number of patients is one of our most frequent criticisms of non-industry-sponsored clinical trial applications at the Ethics Committee of the Vienna University

How can we provide effective training for research ethics committee members? A European assessment

Training for members of research ethics committees (RECs) varies from state to state in Europe. To follow this up, the European Forum for Good Clinical Practice organised a workshop in March 2007 to explore these issues and look for solutions. This article summarises the discussion, providing ways forward to develop REC training.

Sharing and reuse of individual participant data from clinical trials: principles and recommendations

Objectives We examined major issues associated with sharing of individual clinical trial data and developed a consensus document on providing access to individual participant data from clinical trials, using a broad interdisciplinary approach. Design and methods This was a consensus-building process among the members of a multistakeholder task force, involving a wide range of experts (researchers, patient representatives, methodologists, information technology experts, and representatives from funders, infrastructures and standards development organisations). An independent facilitator supported the process using the nominal group technique. The consensus was reached in a series of three workshops held over 1 year, supported by exchange of documents and teleconferences within focused subgroups when needed. This work was set within the Horizon 2020-funded project CORBEL (Coordinated Research Infrastructures Building Enduring Life-science Services) and coordinated by the European Clinical Research Infrastructure Network. Thus, the focus was on non-commercial trials and the perspective mainly European. Outcome We developed principles and practical recommendations on how to share data from clinical trials. Results The task force reached consensus on 10 principles and 50 recommendations, representing the fundamental requirements of any framework used for the sharing of clinical trials data. The document covers the following main areas: making data sharing a reality (eg, cultural change, academic incentives, funding), consent for data sharing, protection of trial participants (eg, de-identification), data standards, rights, types and management of access (eg, data request and access models), data management and repositories, discoverability, and metadata. Conclusions The adoption of the recommendations in this document would help to promote and support data sharing and reuse among researchers, adequately inform trial participants and protect their rights, and provide effective and efficient systems for preparing, storing and accessing data. The recommendations now need to be implemented and tested in practice. Further work needs to be done to integrate these proposals with those from other geographical areas and other academic domains.