Ethics & Quality Systems

Highest National & International Ethical Standards

Research involving human participants is necessary, in order to advance knowledge in the field of biomedical science. However, there are many examples throughout history of human research subjects, being treated unethically and of atrocities in relation to human research having occurred throughout the world.

Therefore, regulations, guidelines and ethical codes of conduct are required to ensure that the rights and welfare of research participants are protected and to ensure that similar events are not repeated. The following sections provide an overview of the important guidelines and legislation with regard to clinical trials, from an Irish and European perspective in particular.

All studies undertaken at the CRC must comply with the highest national and international ethical standards. Specifically all studies must be reviewed and approved by the hospital Research Ethics Committe (REC) prior to initiation.

In this section detailed information on core ethical principles and guidelines is provided. This information has been compiled as part of the Dublin Centre for Clinical Research staff orientation package working group, chaired by Ms. Mary McGrath.

Ethics | Nuremberg Code

The Nuremberg Code, formulated in August 1947, is a set of research ethics principles for human experimentation drawn up as a result of the Nuremberg Trials held at the end of the Second World War. It is a very important document in the history of the ethics of medical research and the first of it’s kind to ensure the rights of subjects.

Specifically, the principals were set in response to the inhumane human experimentation, carried out in concentration camps during the war, by Nazi doctors such as Dr. Josef Mengele. The Nuremberg code includes such principles as informed consent and absence of coercion; properly formulated scientific experimentation; and beneficence towards experiment participants.

The ten points of the Nuremberg Code:

  1. The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understood and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonable to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.
  2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.
  3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.
  4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.
  5. No experiment should be conducted where there is a prior reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.
  6.  The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.
  7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.
  8. Only scientifically qualified persons should conduct the experiment. The highest degree of skill and care should be required through all stages of the experiment of those that conduct or engage in the experiment.
  9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible.
  10.  During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgement required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.

Ethics | Declaration of Helsinki

The Declaration of Helsinki (DoH) is the World Medical Association's best-known policy statement. The first version was adopted in 1964 and has been amended six times since, most recently at the General Assembly in October 2008. The current (2008) version is the only official one; all previous versions have been replaced and should not be used or cited except for historical purposes.

The declaration is not legally binding but the underlying principals have been incorporated into law in some countries. It is a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects.

The key points of the declaration are:

  • In medical research involving human subjects, the well-being of the individual research subject must take precedence over all other interests
  • It is the duty of the physician to protect the life, health, privacy and dignity of the human subject.
  • Medical research involving human subjects must conform to generally accepted scientific principals.
  • Effects on the environment and welfare of animals used for research must be considered.
  • Each experimental procedure should be fully described in a protocol and be considered by an ethical review committee.
  • The research protocol should contain a statement of the ethical aspects of the research study.
  • Medical research must be conducted by scientifically qualified personnel supervised by a clinically competent medical person.
  •  Predictable risks and burdens should be assessed in comparison with foreseeable benefits for the subject and others.
  • Physicians should cease any investigations if the risks outweigh the potential benefits.
  • The importance of the objective should outweigh the risks and burden to the research subject.
  •  The subjects must be volunteers and informed participants.
  • The right of research subjects to safeguard their physical and mental integrity and privacy must be respected.
  • Each potential subject must be adequately informed of every aspect of the research study and their freely given consent sought in writing.
  • For subjects in a dependent relationship with the researcher, informed consent should be sought by an independent physician.
  • For legally incompetent subjects the investigator must seek consent from a legally authorised representative.
  •  Where the legally incompetent subject is able to give assent to decisions about participation in research that assent should be sought in addition to consent of the legally authorised representative.
  • If research is intended on subjects who cannot consent, it must be justified to, and be approved by the ethics committee.
  •  Results of all trials conducted according to these principals should be accurately published and be made available.

Ethics | ICHGCP

International Conference on Harmonisation/Good Clinical Practice (ICH/GCP)

The first principle of ICH GCP is: 

Clinical trials should be conducted in accordance with the ethical principals that have their origin in the Declaration of Helsinki and are consistent with Good Clinical Practice and the applicable regulatory requirements’

Until 1996 there were several documents in existence relating to good clinical practice (GCP). An international committee for the harmonisation of good clinical practice (ICH GCP) was formed to produce a standard, which was agreed by the European Union, Japan and the United States of America. These guidelines were implemented in the participating countries and had the advantage of facilitating mutual acceptance of data by the regulatory authorities of these countries.

The ICH GCP guidelines are very comprehensive and list responsibilities for all involved in research activity. It includes specific sections listing responsibilities of ethics committees, investigators and sponsors. There are also sections detailing the format of trial protocols, investigator brochures and essential documents required for clinical trials.

The ICH GCP guidelines were an attempt to unify GCP standards but they were only ever guidelines and lacked the legal status needed in order that everyone adopted them. Although most sponsor companies adopted the guidelines from the outset there were some that did not.

In particular academic research units found the cost load implications were too great to implement the guidelines. Also some ethics committees were reluctant to adhere to the extra requirements that ICH GCP guidelines made of them, since they were not legally obliged to do so.

However in 2001 the European Union ( EU ) issued a clinical trial directive (2001/20/EC) which required the ICH GCP guidelines to be adopted in local law ensuring that all parties practising research now have to adhere to the guidelines.

The Main Principles Of ICH GCP

  • Before a trial is initiated, foreseeable risks and inconveniences should be weighted against the anticipated benefits for the individual trial subjects and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.
  • The rights, safety and well-being of the trial subjects are the most important consideration and should prevail over interests of science and society.
  • The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.
  • Clinical trials should be scientifically sound and be described in a clear detailed protocol.
  • A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/research ethics committee (REC) approval/favourable opinion.
  • The medical care given to, and medical decisions made on behalf of subjects should always be the responsibility of a qualified physician or, when appropriate of a qualified dentist.
  • Each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective task(s).
  • Freely given informed consent should be obtained from every subject prior to clinical trial participation.
  • All clinical trial information should be recorded, handled and stored in a way that allows its accurate reporting, interpretation and verification.
  • The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement (s).
  •  Investigational products should be manufactured, handled and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.
  •  Systems with procedures that assure the quality of every aspect of the trial should be implemented.

Ethics | European Directive on Good Clinical Practice in Clinical Trials

The EU Clinical Trials Directive of 2001 (2001/20/EC) aimed to harmonise and streamline clinical trial procedures throughout the member states, and relates to all trials involving medicinal products for human use, and encompasses all personnel involved with the clinical trial procedure.

The regulations came into force on 1st May 2004 when a statutory instrument (S.I 190 of 2004) passed the parent EU Regulation into Irish law. These regulations replace those controls that previously applied to such trials under the Control of Clinical Trials Acts, 1987 and 1990. S.I. 190 now governs clinical drug trials in Ireland. (S.I. 190 of 2004 has been amended by S.I. 878 of 2004 and S.I. 374 of 2006.)

Guidance provide by the EU Directive:

  • Properly obtained and documented informed consent must be obtained.
  • Adherence to Data Protection directive 95/46/EEC is required.
  • Indemnity and insurance to cover liability of investigator and sponsor is required.
  • Subjects must be given a contact point from where further information can be obtained.
  • Extensive details relating to the conduct of clinical trials using those unable to give consent.
  • A single ethics committee opinion is required for national multi-centre studies.
  • 60 days maximum is allowed for an ethics committee to provide an opinion (35 days for an amendment).
  • Extension to these approval times apply when studies involve gene/cell therapies.
  • A database with details of European trials and adverse health events will be set up.
  • Adverse event reporting to be standardised.
  • GCP inspections to become mandatory.
  • Controls to be placed on the manufacture and labelling of investigational products.
  • Studies can be stopped in the event of sponsor and/or investigator non-compliance.

Ethics | Data Protection

Data protection pertains to the individual’s fundamental right to privacy. The Irish Data Protection Office (DPO) states that “anonymisation of patient records and/or freely given and informed patient consent to access records for the purposes of research are the foundation stones of how the DPO wishes to see medical research undertaken from a privacy perspective”

Data Protection Acts

The main Irish law dealing with data protection is the Data Protection Act 1988.  The 1988 Act was amended by the Data Protection (Amendment) Act 2003.  An informal consolidated version of the two Acts is available. The 2003 Amendment Act brought our law into line with the EU Data Protection Directive 95/46/EC. All Sections of the Acts are in force, except Section 4 (13) (enforced subject access).

Anyone processing personal data must comply with the 8 data protection principles of good practice:

  1. Data must be fairly and lawfully processed
  2. Data must be obtained for specified explicit and legitimate purposes
  3. Data must be processed in ways compatible with the purpose for which it was first given to you
  4. Date must be held securely
  5. Data must be accurate and up-to-date
  6. Data must be accurate, relevant and not excessive
  7. Data must not be kept for longer than necessary for the specified purpose
  8. Data must be provided to the subject upon request

In the case where data is being transferred to countries outside the EU, the researcher must ensure that the country in question provides an adequate level of data protection.

The nature of research implies that there is a large amount of paper and electronic data held about the research subject. Research staff, have a responsibility to their research subjects and their employer regarding data protection

  1. Data should be stored in a secure room
  2. Data must be locked away if unattended
  3. No one should access subject data unless authorised to do so by research personnel and/or data protection officer
  4. Research subject confidentiality should be maintained by the use of initials and/or research numbers as unique identifiers on research material.
  5. Electronic data must be password protected.Personal data that could potentially identify research subjects should be kept in a secure place, separate from research files.