Ethics committee registration and re-registration with the regulatory authority in India.

Background: All ethics committees (ECs) that review and monitor clinical trials in India must be registered with the regulatory authority. We ascertained the status of registration and re-registration of ECs till December 2017. Methods: The ECs registered and re-registered with the Indian regulatory authority till December 2017 were extracted. The status of ECs was analysed according to the state, institute category and registration. Results: A total of 1260 ECs were registered, of which 14% were based in medical colleges, 2% in dental colleges, 61.2% in hospitals other than medical colleges and 8% as independent ECs. Of the recognized medical and dental colleges, only 37.3% and 10.9%, respectively, and 45.9% of ECs from teaching hospitals (other than medical and dental colleges) had registered with the regulatory authority. Of the 911 ECs eligible for re-registration, 516 (56.5%) had reregistered. Conclusion: A low proportion of registrations ofECs from eligible academic health institutions raises concern about adherence to regulatory guidelines and conduct of clinical trials in India. The lower re-registration of ECs helps in the identification of factors which should be addressed to facilitate clinical research in India.

[Joint pilot project of the German higher federal authorities and ethics committees on implementing the EU Regulation on clinical trials]. / Gemeinsames Pilotprojekt von Bundesoberbehörden und Ethikkommissionen zur Umsetzung der EU-Verordnung zu klinischen Prüfungen.

BACKGROUND: The European Clinical Trials Regulation 536/2014 and the corresponding national legal transitions will require close cooperation between the federal higher authorities and ethics committees in the assessment of clinical trial applications involving medicinal products in humans. In preparation for this, a pilot project was launched to simulate the future processes of the regulation in line with current legal requirements and in order to give applicants, authorities and ethics committees the opportunity to familiarise themselves with the new procedures. OBJECTIVES: The aim of this paper is to examine all pilot project procedures of the first year since starting the pilot project at the end of 2015. MATERIALS AND METHODS: All 20 pilot projects completed in the first year were analysed for adherence to deadlines and results of the assessments. RESULTS: Within the time limits specified in the EU regulation, 17 of 20 procedures were fully completed. In two cases, the sponsors slightly exceeded the additional delivery period. In one case, the sponsor withdrew the application within the pilot procedure. All 20 applications were processed jointly by the federal authorities and ethics committees, and in all cases a coordinated assessment report was successfully compiled on time. All 20 applications were approved, five of which were subject to suspensive conditions. CONCLUSIONS: Compliance with the deadlines set by federal authorities and ethics committee shows that the technical infrastructures and processes established in the pilot procedure are fully functional. The cooperation between the federal higher authorities and ethics committees was very successful from the perspective of the parties involved.

[The impact of the EU Regulation 536/2014 on the tasks and functioning of ethics committees in Germany]. / Die EU-Verordnung 536/2014 und ihr Einfluss auf die Aufgaben und Arbeitsweisen der Ethikkommissionen in Deutschland.

The EU Clinical Trial Regulation 536/2014 (CTR) and its implementation in Germany led to substantial changes of the established, well-accepted and effective system of reviewing clinical trial applications by ethics committees (ECs), which impair their independence. For the first time, the German federal legislator specified in detail the composition, functioning, tasks and responsibilities of ECs. ECs have to be registered with the federal drug authority BfArM and if an EC does not perform properly the registration can be withdrawn. In addition, the drug authorities may override the negative opinion expressed by an EC. The ECs will also lose their financial autonomy as the fees will be fixed by the federal government. The tasks and responsibilities of the ECs remain almost entirely unchanged, however. The ECs remain involved in the assessment of both parts of the application dossier. Part I is assessed together with the drug authorities, the drug authorities having the lead. The assessment of part II remains the sole responsibility of the EC. As the deadlines for the assessment became rather short, in particular for multinational trials, and the communication with the sponsor will be in writing only, the established procedures of ECs have to be modified. Up to now it was common to verbally discuss problematic issues with the sponsor. The CTR is focused on written communication with the sponsor via the EU portal. ECs, their office staff and chairpersons will need considerable professionalism and respective training. The future workflow requires substantial IT support. The ECs and the Association of Medical Ethics Committees in Germany will do their utmost to protect efficiently the research subjects and to promote Germany as a major destination for clinical research.

[Changes in the German Medicinal Product Act imposed by the EU regulation on clinical trials]. / Änderungen des Arzneimittelgesetzes durch die EU-Verordnung zu klinischen Prüfungen.

The entry into force of Regulation (EU) No. 536/2014 of the European Parliament, the Council of 16 April 2014 for clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC necessitated amendments to the national legislation on medicinal products. These changes mainly concern the sixth chapter of the German Medicinal Products Act (Arzneimittelgesetz, AMG) and the elimination of the GCP (good clinical practice) ordinance for clinical trials that will be covered by the regulation in the future. Sections 41a, 41b and 41c, which came into force in December 2016, regulate the registration procedure, the procedural rules and the business distribution plan according to which the responsibilities of the registered ethics committees for the authorisation procedures will be determined and cooperation with the federal higher authorities will be handled. All other amendments in the sixth chapter will not enter into force until the date of application of the regulation - presumably in the fourth quarter of 2018. In the future, Section 40a will regulate the general prerequisites - in particular the basic procedures for cooperation between the federal higher authority and the ethics committees - in addition to the provisions of the regulation. Section 40b governs special prerequisites for clinical trials and contains, in particular provisions for the informed consent in clinical trials with minors and incapacitated adults. Further changes concern, among other things, the transfer of previous regulations of the GCP ordinance into the AMG and adjustments regarding reporting obligations in the context of clinical trials in the AMG.

Trials, Regulation and tribulations.

INTRODUCTION: Regulation EU 536/2014 EU introduces a separation between two parts (technical-scientific aspects and locally relevant ethical aspects) in the assessment of applications for approval of trials and provides for each 'Member State concerned' to arrive at 'one single decision' regarding the application for authorisation to conduct a trial. PROPOSALS: The Regulation should be implemented in such a way as to avoid a separation between scientific assessment and ethical assessment; guarantee the absence of conflicts of interest in the institutions responsible for decision-making; promote efficiency on the part of ethics committees. In particular, (i) it is not appropriate to assess Parts I and II of the application for approval to conduct a trial separately (scientific soundness is the principal requisite for ethical soundness); (ii) conflicts of interest should be avoided, especially as regards links with the national authority responsible for drugs regulation; (iii) decision-making in each state should be the responsibility of a single coordinating ethics committee divided into sections specialising in different therapeutic fields; (iv) local committees affiliated to institutions where trial participants are recruited should be able to interact with the coordinating committee, provide consultation services-including on issues of clinical ethics-and promote training in the field of biomedical ethics.

Development of guidelines for the conduct of HIV research monitoring by ethics committees in Nigeria.

Nigerian research ethics committees are charged with the responsibility to monitor ongoing research to ensure compliance with ethical standards. Recent evidence from qualitative studies on research conduct however, indicate that many research studies fail to implement their protocols as written, and that this is not reported due to a failure of comprehensive monitoring. As Nigeria is in many respects a highly suitable country in which to conduct HIV biomedical prevention research, we argue there is a need to reprioritise the strengthening of the monitoring capacity of ethics committees so that such vital and ethically complex research can be conducted with confidence. We identify the need for (i) improved resourcing and training of ethics committee members, and (ii) comprehensive planning of research monitoring as part of the ethics committee protocol review process. We also highlight the significance of community collaboration and the establishment of a central pool of national monitors, as essential components for reinvigorating monitoring capacity.

[Informed consent to the insertion of a PEG tube in a 53-year-old male patient with highly advanced dementia]. / Aufklärung und Einwilligung zur Anlage einer PEG Sonde bei einem 53 jährigen Patienten mit fortgeschrittener Demenz.

In patients with advanced dementia and dysphagia, regular fluid- and food intake together with oral medication can be guaranteed by insertion of a PEG tube. Consent to a treatment in a patient without legal capacity requires nomination of a legal substitute by an Austrian court. The following case report describes the problems associated with this particular situation exposing additional psychosocial stress to closest relatives and to the palliative care team in charge for the patient. This case report describes the legal options together with the finally chosen path of medical treatment which in clinical praxis may not always match.

How to ascertain drug related deaths during clinical trials ?

Recent guidelines by the Drug Controller General of India require extra care by Investigators & Sponsors of Clinical Trials in India. The author, an eminent member & Chairman of various Independent Ethics Committees in Mumbai, proposes various concrete solutions for adherence to these guidelines. Insurance cover to the subjects, use of Internet databanks for drug interactions, active involvement by the pharmacologists in Ethics Committee, review of data from animal studies, being amongst them. In case of death due to trial, autopsies, or at least verbal autopsies, are essential in the interest of Science and Law. More importantly Anticipation and prevention of ADEs can be done by exclusion of subjects from trials by using newer technologies like cDNA in microarrays to determine several polygenic quantitative trait loci (QTLs) and tests for Single Nucleotide Polymorphisms (SNPs). Drug manufacturers must provide prototypes of Affymetrix chips to clinicians and bear the cost in their own enlightened self-interest.

The judicial process: an overview from the TDA Council on Ethics and Judicial Affairs.

From time to time, the Council on Ethics and Judicial Affairs must investigate and act on the alleged unethical behavior of Texas Dental Association members. Because the alleged behavior is directed at a colleague and TDA member, the work of the council is neither comfortable nor inviting. Nonetheless, council decisions are made taking into account its mission to investigate the allegation between the parties and to improve dental ethics in the state.

Preserving Do No Harm: Supreme Court Tosses Challenge to Medical Ethics Committee Law.

Twenty years after it took effect, Texas' medical ethics committee review law has withstood challenge after challenge. The Texas Supreme Court is on the verge of ending the latest high-profile attack on the law that ensures physicians can uphold their professional obligation to "do no harm." In October 2019, the state's high court declined to take up Kelly v. Houston Methodist Hospital, in which the mother of a deceased patient attempted to overturn a provision of the Texas Advance Directives Act. Justices' action leaves intact an appeals court decision that preserves physicians' ability to use their medical judgment in end-of-life cases.

Will medically-assisted suicide mean the rebirth of (clinical) ethics committees in Italy?

The Italian Constitutional Court has held that, in certain specific circumstances, prosecution for assisted suicide, regulated by Article 580 of the Criminal Code, is not compatible with the Constitution. The circumstances in question relate to individuals who are being kept alive by life-sustaining treatments, who are fully capable of taking free, informed decisions and are suffering from irreversible conditions that are a source of intolerable physical or mental suffering. The Court has held that the Ethics Committees must assess a request for assisted suicide made by an individual meeting these conditions. The decision requires the identification of the Ethics Committee authorised to issue authorisation in such cases and a guarantee that these Ethics Committees are able to deal with this type of issue. The Court's decision is an important opportunity to establish and promote clinical Ethics Committees, which are not nationally regulated in Italy and exist in very small numbers in only a few parts of the country.

[Chances and limitations of patients' advance decisions at the end of life]. / Möglichkeiten und Grenzen antizipierender Willenserklärungen am Lebensende.

Death by "natural" causes is not appreciated in Western industrialized countries because it may be regarded as an obstacle against performance and consumption. In addition, life-saving therapies for patients with an infaust prognosis are often rather expensive and therefore classified as "futile". Utilitarian measures for the individual's quality of life (QALY's), which are allegedly objective, veil the fact that they can only reflect the parameters that have been considered during their construction. Caused by fear of a life in the nursing home, which is partially intensified by the media, many ethicists and lawyers propagate anticipating models of retaining patients' autonomy at the end of life. Apart from general considerations published by the former National Ethics Council in 2005, the German Parliament in 2009 will have to discuss three different bills concerning patients' advance decisions to refuse medical treatment. The illusion of "autonomous dying" is not a convincing model for the end of life debate.

[Responsibility and function of Research Ethics Committees]. / Aufgaben und Arbeitsweise Medizinischer Ethik-Kommissionen.

In Germany, only Research Ethics Committees (REC) set up according to States law at Faculties of Medicine, Medical Associations or States authorities are entitled to assess all areas of biomedical research. In a multidisciplinary review, research projects are evaluated using the criteria "scientific quality", "accordance with law" and "ethical acceptability". Since 2004, the "favorable opinion" of a REC is together with the approval by the competent Federal Authority a legal requirement for drug trials. For all other fields of biomedical research, the opinion of a REC is considered legally not binding advice for the researcher. For sharing of experiences, for harmonization of their work and for partnership with the public, the local-independent RECs established the "Permanent Working Group of German Research Ethics Committees". This group functions to a certain degree like central RECs in other States.

Impact of recent legislative bills regarding clinical research on Italian ethics committee activity.

AIMS AND BACKGROUND: The present work assessed the impact of two decrees on ethics committees in Italy, aimed at bringing the national laws on the conduct of clinical trials into line with the rest of the EC, and regulating and facilitating not-for-profit research. MATERIAL AND METHODS: Prospectively collected data from an Italian multicentre study were examined with respect to the ethics review process. Administrative and time elements of the review process were audited. Main outcome measures were time between the application submission and the ethics committee definitive opinion, type and number of application submission forms, number of ethics committees that refused fee exemption, and time between the ethics committee approval and the administrative authorisation. RESULTS: A total of 134 local research ethics committees (LRECs) were approached. Application submission procedures and application forms varied greatly; paper submission was mandatory. The median time from submission to approval was 72 days. Only two LRECs refused the fee exemption. The median time from LREC approval to administrative agreement was 50 days and only 9.6% of local authorities came to a verbal agreement with the sponsor. CONCLUSIONS: Italian LRECs are still not sufficiently efficient in complying with the Directive 2001/20/EC requirement (60 days). Better coordination of LRECs work is needed although the optimal level of coordination between them is still not known. In the meantime, national guidelines are needed concerning the application of Directive 2001/20/EC. The behaviour of Italian LRECs towards not-for-profit research was excellent although only the fee exemption was requested.

[Setting up of a Clinical Research Centers Ethics Committee in Rhône-Alpes-Auvergne district]. / Création d'un comité d'éthique des Centres d'Investigation Clinique en région Rhône-Alpes-Auvergne.

OBJECTIVE: French law on biomedical research does not apply to non-interventional researches. A favourable advice of an IRB (Institutional Review Board) is required. This article describes the setting up of a Clinical Research Centers Ethics Committee. METHODS: The Clinical Research Centers Ethics Committee (CRCEC) was created in November, 2006. To guarantee a better objectivity Grenoble's projects are reviewed in Clermont-Ferrand board and conversely. Recommendations are given according to the compliance of research with laws and regulations in effect in France. RESULTS: Twenty eight projects were submitted to the CRCEC during a 18 months period, mainly observation studies in a hospital setting. Four projects were redirected towards a formal French Ethic Committees (CPP) submission. Requests of modifications concerned a lack of information relative to data confidentiality. CONCLUSION: This committee is useful but its voluntary and "unofficial" nature questions about its perpetuation. We suggest that non interventional research be submitted to official CPP.

Consideration of the gestational carrier: an Ethics Committee opinion.

Intended parents engage with gestational carriers in an attempt to achieve their personal reproductive goals. All gestational carriers have a right to be fully informed of the risks as well as the contractual and legal aspects of the gestational-carrier process. Gestational carriers have autonomy in making their own decisions regarding medical care and should be free from undue influences by the stakeholders involved. They should have free access to and receive psychological evaluation and counseling before, during, and after participating. Gestational carriers require independent legal counsel regarding the execution of contracts. This document replaces the document of the same name, last published in 2013 (Fertil Steril 2013;99:1838-1841).

Threats to bioethical principles in medical practice in Brazil: new medical ethics code period.

We aimed to outline the profile of medical professionals in Brazil who have violated the deontological norms set forth in the ethics code of the profession, and whose cases were judged by the higher tribunal for medical ethics between 2010 and 2016. This survey was conducted using a database formed from professional ethics cases extracted from the plenary of the medical ethics tribunal of the Federal Council of Medicine. These were disciplinary ethics cases that were judged at appeal level between 2010 and 2016. Most of these professionals were male (88.5%) and their mean age was 59.9 years (SD=11.62) on the date of judgment of their appeals, ranging from 28 to 95 years. Most of them were based in the southeastern region of Brazil (50.89%). Articles 1 and 18 of the medical ethics code were the rules most frequently violated. The sentence given most often was the cancellation of their professional license (37.6%) and the acts most often sentenced involved malpractice, imprudence, and negligence (18.49%). It is acknowledged that concern for the principles of bioethics was present in the appeal decisions made by the plenary of the medical ethics tribunal of the Federal Council of Medicine.

Misconduct in third-party assisted reproduction: an Ethics Committee opinion.

Professionals who discover misconduct or other undisclosed information that would be material to the participation of another party (such as a donor, gestational carrier, intended parent, or lawyer) in an assisted reproductive technology arrangement should encourage disclosure to that party. In some instances, it is ethically permissible for the physician either to disclose material information to the affected party or to decline to provide care. In all cases involving the legal status or rights of the parties, referral to legal professionals is advised. This document replaces the document of the same name, last published in 2014 (Fertil Steril 2014;101:38-42).