GCP Good Clinical Practice Update March 2024 PDF

GOOD CLINICAL PRACTICE (GCP) Prof. dr. Jarir At Thobari, DPharm, PhD 1Dept. Pharmacology & Therapy Div. Pharmacoepidemiology, Pharmacovigilance & Pharmacoeconomic 2Clinical Epidemiology and Biostatistic Unit (CEBU) 2Indonesia Cochrane Center (ICC). Faculty...

GOOD CLINICAL PRACTICE (GCP) Prof. dr. Jarir At Thobari, DPharm, PhD 1Dept. Pharmacology & Therapy Div. Pharmacoepidemiology, Pharmacovigilance & Pharmacoeconomic 2Clinical Epidemiology and Biostatistic Unit (CEBU) 2Indonesia Cochrane Center (ICC). Faculty of Medicine, Public Health & Nursing Universitas Gadjah Mada  Understand origin and evolution of ICH GCP Define Good Clinical Practices Learning Recognize the need for ethics and quality in human research Objectives Understand the ethical and quality principles to be followed for research involving human participants Describe basic framework of GCP Research and development process  A brief look at history Sulfanilamide WWII Thalidomide Guatemala Tuskegee 1938 1939-1945 1956-1962 1946-1948 1932-1972 Nuremberg Belmont Code Report 1947 1979 Willowbrook Jewish Hospital Trovan Asthma study TGN1412 1963-1966 1963 1996 2001 2006 Ethical Standard for Clinical Study 1996 ICH 1979 GCP Belmont 1964 Report Declaration of Helsinki 1947 Nuremburg Code 5  The need of standardization Product development is expensive, time consuming Need for safe and efficient products for various health problems; for efficient quality systems in the testing of product Existence of national laws and regulations for drug development Global drug market  Harmonization (ICH) Harmonize product registration requirements Unified standard Mutual acceptance of clinical data by the regulatory authorities  ICH- Good Clinical Practice ICH is the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH-GCP is Good Clinical Practice guidelines agreed at the conference Thus, was born GCP GCP Guidelines were developed to ensure that only adequately planned and conducted clinical studies are performed, thus safeguarding the interests of the patients, investigator, sponsor and regulator.  Subject’s safety could be jeopardized. The result would be bias. Risk and Implications The data could not be use for National Drug Authority (NDA)/Regulatory Authority (RA) application. What would happen if the standards are not The product could not be marketed. followed? The safety profile of the product are not well-known. The Investigator have bad reputation.  GCP Adoption in Asia Original ICH GCP 1996 GCPs in Asia: Singapore GCP 1998 Malaysian GCP 1999 Chinese GCP 1999 Thailand 2000 Indonesia 2001  What is GCP? An international ethical and scientific quality standard Trials that involve participation of human subjects GCP Basic Principles ETHICS QUALITY  When is GCP applicable? This guideline should be followed CRITICAL when generating clinical trial data that are intended to be submitted to regulatory authorities. ALWAYS Basic principles of Ethics and Quality are to be applied to any research that may have an impact on the safety and well-being of human subjects. Applicable standards in biomedical research B Implementation a Animal research s studies i QPBR Pharmaceutical product research and development c QPBR GLP GCP GCP r Preclinical Clinical Regulatory Post-marketing e In vitro Discovery development development authority (Pharmaco- s studies (Safety) (Safety & efficacy) registration vigilance) e QPBR a r Manufacturing Production c Epidemiology QPBR GMP GMP h studies Clinical studies GCP Public health research GCP :Regulatory requirement  IRB/IEC Medical care by Clear scientifically approval Qualified Dr sound protocol Qualified personnel Informed consent Adequate previous data Data accurate, verifiable Rights safety and wellbeing of Subject subjects confidentiality Risk vs benefit Investigational weighed at the product start Ethical Quality principles DoH GCP control 16 Principle 1 – Ethical Principle Conducted in accordance with Ethical principles Origin in the Declaration of Helsinki Laws and regulations Consistent with Ethical GCP Standards GCP Protocol Applicable regulatory requirements  Principles of Research Ethics Respect for Beneficence/non- Justice person: Autonomy maleficence The obligation to Treating Respecting ensure safety, well- everyone with someone's right being, maximize appropriate and to make their benefits, and righteous own choices minimize harm morals  Declaration of Helsinki Ethical guidance for study involving in human participation Safeguarding research participants Informed consent Benefit > risk Use of plasebo Vulnerable participants Post trial access to treatment Research protocol Publishing finding & trial’s registering Ethical committee Privacy and confidentiality Unproven intervention  Unproven Interventions in Clinical Practice In the treatment of an individual patient, where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorized representative, may use an unproven intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering. This intervention should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all cases, new information must be recorded and, where appropriate, made publicly available. Principle 2: Before initiation of trial should perform risk-benefit analysis Initiate and continue the trial only if anticipated benefits justify the risks Principle 3: Safe guarding the participants Protection of rights, safety and well being of trial subjects MUST always prevail over interests of science and society  Principle 4 Adequate Previous Data Adequate non-Clinical (Lab and animal studies) and Clinical Information on the Investigational product (Investigator Brochures) Support Proposed Clinical Trial  Principle 5: Scientific Protocol Clinical trials should be scientifically sound, and described in a clear, detailed protocol By definition, is a document that describes the objective(s), design, methodology, statistical considerations and organization of a trial  Protocol – ICH GCP A document that describes the objective(s), design, methodology, statistical considerations and organization of a trial (ICH 1.44) Selection and General Background Trial/Study Objectives Withdrawal of Information Information Design Subjects Direct Access to Treatment of Assessment of Assessment of Statistics Source Subjects Efficacy Safety Data/Documents Quality Control Data Handling Financing & Publication and Quality Ethics and Record Insurance* Policy* Assurance Keeping 05/03/2024 Principle 6 – Ethical Committee A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favourable opinion. Principle 7: Qualified Physician Medicare for Participants Responsibility of qualified physician  Principle 8: Qualified Trial Personel Everyone involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s). Principle 9: informed consent Informed Consent is a process…. Information Comprehension Decision making – voluntariness, competence BEFORE AND DURING THE STUDY Allow participants to decide  Contents of Statement that the Trial treatment, Informed study is research Purpose of the trial randomization probability Consent Description of Experimental part of procedures including Subject’s responsibility the trial all invasive procedures All written information provided to participant during the process of Foreseeable Alternative procedures obtaining informed risk/inconveniences to Expected benefits or treatment available consent subjects with risks and benefit  Compensation or treatment available in Voluntary nature, right case of trial related Confidentiality to refuse/ withdraw injuries and anticipated expenses, if any Content Informed Access to original medical records to Will be informed in a timely manner, of all Contact person for further information on Consent monitors, auditors, IRBs and Regulators information relevant to participation trial, rights, trial related injuries Foreseeable Approximate number of circumstances that the Expected duration of subjects involved in the subject’s participation participation trial may be terminated 05/03/2024 Principle 10: Quality of data Recorded Accurate Study Data/ Handled Interpretation Information Verification Stored Good Documentation Practice (GDP) Contemporaneous Legible Original Attributable ALCOA Accurate Good Documentation Practice Attributable: It should be clear who created a record and when. It should be clear as to who amended a record, when, and why. Legible: easy to be read. Contemporaneous: created without delay, the evidence or test results are recorded as they are observed. Original: Transcription (from original to second version) is a process where people often make errors, so the original document is most reliable. The original is the first place the information it is written. Accurate: Make sure of the information that you are recording is correct and make sure you’re telling the “whole truth”. Principle 11: Respect participant confidentiality Confidentiality of records that could identify subject should be protected Respecting the privacy in accordance with applicable regulatory requirements Principle 12: Investigational Product Manufacturing Good Handling Manufacturing Storage Practice Approved Usage Protocol Principle 13: Quality Assurance Systems/Procedures set-up (Standard Operating Procedures) To assure the quality of all trial aspects Good Clinical Practice Responsibility Responsibility Investigator Sponsor Investigator’s Brochure Good Clinical Practice Framework DSMB Clinical Data Monitor Management Sponsor Investigator  Conclusions ICH GCP is an international ethical and scientific quality standard Basic principles are Ethics (protection of rights, safety and well being of participants), and Quality (data quality. Credible and integrity) Clinical trial subject's protection is safeguarded through risk/benefit assessment, independent review and approval of clinical trial protocol by Ethics committee and study conduct by qualified personnel Provides framework and defines responsibilities of EC, Investigator and Sponsor