3 Content Historical perspective Origins of ICH / GCP Principles of GCP Informed consent
4 Historical Perspective Nuremberg Code (1948)Kefauver-Harris Amendment (1962)Declaration of Helsinki (1964)International Conference on Harmonization (ICH) – (1990’s)Nuremberg Code (1948) is a set of 10 research ethics principles for human experimentation set as a result of the Subsequent Nuremberg Trials at the end of the Second World War. Specifically, they were in response to the inhumane Nazi human experimentation carried out during the war by individuals such as Dr. Josef Mengele and included trails such as the; twin experiments, hypothermia experiments, pain tolerance. The Nuremberg code includes such principles as informed consent and absence of coercion; properly formulated scientific experimentation; and beneficence towards experiment participants.Kefauver-Harris Amendment "Drug Efficacy Amendment" (1962 – US) Enacted following the Thalidomide tragedies / deformities in Europe.Amendment put regulatory controls on drug manufacturers & required them to provide:Drug efficacy (effectiveness) and safety dataAccurate disclosure of information & advertising about side effectsStopped cheap generic drugs being marketed as expensive drugs under new trade names as new"breakthrough" medicationsPatient Informed Consent was mandatedAdverse advents reactions were required to be reported(The law was signed by President John F. Kennedy on October 10, 1962)Estes Kefauver considered the Amendment his "finest achievement" in consumer protectionDeclaration of Helsinki – developed June 1964 (Finland) by World Medical Association (WMA) set out ethical principles for medical community regarding human experimentation.Known as the cornerstone of human research ethics although not legal binding instrument in international lawFundamental principle – respect for individual, self determination and right to make informed choiceInvestigators responsibility is to patient or volunteer & ethical principles must always take precedence over laws and regulations.Revised x6 times and in Oct 2008 FDA announced the declaration of Helsinki was to be substituted by the ICH / GCP Guidelines because of the Declarations restrictive stance on placebo-controlled trials in economically developing countries.All three are the basis for the Code of Federal Regulations & FDA
5 Principles of ICHAimTo increase international harmonisation, ensuring good quality, safe and effective medicines are developed and registered in a cost effective manner, prevention unnecessary trials & minimising use of animalsGuidelinesQuality, Safety, efficacy, multi-disciplinary regulatory communicationsx12 Efficacy topicsincluding E6: GCP(1990 – Europe, USA & Japan, regulatory bodies & research industry met in BrusselsX 12 Efficacy topicsExposure, Clinical safety, Safety reports, dose response, ethnic factors, GCP, special trial population, general considerations, statistical principles for clinical trials, choice of control group, paediatrics, therapeutic categories
6 ICH definition - GCP"A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected"ICH E6 1.24
7 Good Clinical Practice - GCP What is GCP?International ethical and scientific quality standards for designing, conducting, recording and reporting trials that involve participation of human subjectsWhy is it needed?To ensure that the RIGHTS, SAFETY and WELLBEING of the trial subjects are protectedEnsure the CREDIBILITY of clinical trial dataWhy has it developed into formal guidelines?Public disasters, serious fraud and abuse of human rightsWas developed with consideration of current GCP of the European union, Japan, US, Australia, Canada and Nordic countries and WHOPrinciples:Should be used when generating clinical trial data that are intended to be submitted to regulatory authoritiesTrials should be conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and that are consistent with GCP and regulatory authorities.Participants safety, well being most importantScientifically sound trialsComply with EC and review committeesMedical care responsibility of physicianIndividuals conducting trial should be qualifiedInformed consent should be freely given & obtainedTrial information, drugs locked and stored accordinglyConfidentialObjectives:Ethics = rights of participantsSafety = protection of participantsEfficacy = utility of productCredible & accurate dataUnderpinning principles (x13)
8 ICH/GCP in New ZealandNZ regulatory framework based on Europe’s systemNZ adopts majority of European ICH/GCP guidelinesCountry specific requirements to be taken into account (i.e. MEDSAFE, S.C.O.T.T., EC regulations)New guideline Clinical trials - regulatory approval and good clinical practice requirementsComes into effect on 1 January, 2011SCOTT – Approval from the Standing Committee of Therapeutic Trials (SCOTT) is required if the project involves the use of pre-registration medicines. The study sponsor is responsible for obtaining SCOTT approval and SCOTT gives its approval pending ethics approval of the study. A copy of the ethics committee approval, when granted, is forwarded to SCOTT who then authorise the distribution of non-registered compounds.Medsafe is the New Zealand Medicines and Medical Devices Safety Authority. It is a business unit of the Ministry of Health and is the authority responsible for the regulation of therapeutic products in New Zealand.
9 Informed ConsentA process by which a subject voluntarily confirms his/her willingness to participate in a trial having been informed of all aspects of the trialInformed consent is documented by means of a written, signed and dated informed consent formA process by which a participant voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the decision to participateInformed consent is documented by means of a written, signed and dated informed consent form
10 Informed Consent Process of information exchange Who’s responsibility Capacity to receive informationSufficient timeWithout coercionBenefits (procedures/treatments)RisksProxy consentWitness for oral consentWhat is informed consentIC is more than just a signature on a form, it is a process of information exchange that may include participant recruitment materials, verbal instructions, questions/answer sessions and measures of subject understanding .. Rather than an end point, the consent documentation should the basis for a meaningful exchange between the investigator and the participate.Research cannot be conducted unless IC obtainedCapacity of individual to give IC should be access on a case by case basisResponsibility: The researcher, investigator, or a person designated by the investigator should fully inform the subject .. Of all pertinent aspects of the trial including the written information.The consent process:Subjects must receive all available informationLanguage must be understandable to the subjectSubjects must ‘understand’ all informationProvision must be made for language/translationsSubjects must have sufficient time to considerNo coercion or undue influenceShould include:- benefits- procedures and/or treatments- documented on consent formsProxy consent –provided by another person on behalf of an incompetent patient – with physical or metal incapacityWitness for oral consent “NZ law individual to give consent”