Assalamu`alaikum and greetings to all…
When we talk about Good Clinical Practice (GCP), it is all about patient’s safety and data integrity. The Malaysian Guideline for GCP and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH GCP) are correlated. Honestly, to attend this kind of workshop is too mainstream for novice nurse like me. All the technical terminologies are focus more on the medical practitioners like Physician, Medical Officer, and Pharmacist. When I was surrounded by UD52, UD48, UD44, UD41.. I asked myself this question – What the heck am I doing here? This is not the place where I belong! Anyway, it was a good exposure and please do not ask me to attend this workshop again. So here, I am going to share my short term memories about it.
The Principles of ICH GCP
Clinical trials should be conducted in accordance with the:
- Ethical principles that have their origin in the Declaration of Helsinki
- Consistent with GCP
- Applicable regulatory requirements
Before a trials is initiated:
- Foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society.
- A trial should be initiated and continued only if the anticipated benefits justify the risks:
- Risk to individual subjects are minimised
- Benefits to individual subjects are enhanced
- Benefits to individual subjects and society are proportionate to or outweigh the risks
The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibilities of:
- A qualified physician (Consultants, Specialists, Medical Officers, Dental Officers)
- Principal Investigator
- Sub-investigator
- A qualified dentist
Each individual involved in conducting the trial should be qualified by:
- Education
- Training
- Experience to perform his/her respective tasks
Institutional Review Board/Independent Ethics Committee (IRB/IEC) ≠ Regulatory authorities (eg. NPCB)
In Malaysia, IRB/IEC is known as MREC (Medical Research and Ethics Committee). The composition:
- At least 5 members
- At least 1 member whose primary area of interest is in a nonscientific area
- At least 1 member who is independent of the institutional/trial site
Responsibilities:
- Obtain and review study documents:
- Study protocol
- General information of trial
- Background information
- Trial objectives and purpose
- Trial design
- Selection and withdrawal of subjects
- Treatment of subjects
- Assessment of efficacy
- Assessment of safety
- Statistic
- Direct access to source data/documents
- Quality control and quality assurance
- Ethics
- Data handling and record keeping
- Financing and insurance
- Publication policy
- Supplements
- Informed consent form
- Subject recruitment procedures
- Written information to subjects
- Investigator’s Brochure (IB)
- A compilation of the clinical and nonclinical data on the IP that are relevant to the study of the products in human subjects
- Concise, simple, objective, balanced and nonpromotional
- Provides information to understand IP, rationale for administrative of IP, safety measures, insight to support clinical management of subjects, unbiased risk-benefit assessment
- Payment and compensation to subjects
- Investigator’s CV
- Verify qualifications of investigator
- Conduct continuing review of on-going trials
- Review amount and method of payments to subjects
- Retain all records for at least 3 years after completion of trial
Investigator The investigator should be qualified by:
- Education
- Approved training in GCP
- Experience to assume responsibility for the proper conduct of the trial
Informed consent of trial subject and Patient Information Sheet (PIS) should include 20+1 explanations of:
- Trial involves research
- Purpose of the trial
- Probability for random assignment to treatment
- Trial procedure to be followed, including invasive procedures
- Subject’s responsibilities
- Experimental aspects of the trial
- Description of foreseeable risks or discomforts
- Expected benefits
- Alternative procedure/treatment available
- Subject compensation
- Anticipated prorated payment
- Anticipated expenses
- Subject’s participation in the trial is voluntary – subject may withdraw at any time
- Direct access to subject’s original medical records
- Records identifying the subject will be kept confidential
- Will be update if new information becomes available
- Person(s) to contact for further information and in the event of trial-related injury
- Circumstances for trial termination
- Duration of participation in trial
- Number of subjects involved in the trial
- The source of the investigational product (IP) that may be culturally unacceptable
Safety reporting
- All 6 serious adverse event (SAE) detected or being notified should be reported immediately (within 24 hours) to the sponsor:
- Result in death
- Is life-threatening
- Requires inpatient hospitalization or prolongation of existing hospitalization
- Results in persistent or significant disability/incapacity
- Is a congenital anomaly/birth defect
- Other important medical events based on medical and scientific judgment
- Sudden unexpected serious adverse reaction (SUSAR) that is fatal/life threatening – initial report must be not later than 7 calender days, followed by a complete report within 8 additional calender days (sponsor → NPCB)
- Report Number and indication Initial report or Follow up
- NMRR ID and protocol title
- Principal investigator name and designation
- Subject ID
- Study site/institutional name/country
- Adverse Event type, description of event, action taken and outcome
- Name of suspect medicinal product
- IP Causality
- All other SUSAR and local SAE, written report no later than 15 calender days from awareness of event by investigator
Respect for trial subject:
- Protect subject’s confidentiality and privacy
- Provide opportunity to withdraw early, without penalty
- Subject’s well being monitored
- Inform subject of new information, and to re-consent if necessary
- Inform subject the study results, in recognition of his/her contribution to research
- Compensate subject for research injury
Responsible for IP accountability:
- The investigator can assign the responsibility to pharmacist or appropriate person under supervision of IP
- Maintain record of IP
- Stored IP as specified by spnsor
- Explain correct use of IP to subjects
Premature termination of a trial:
- Promptly inform subjects or institution (if necessary)
- Written explanation to MREC, sponsor, NPCB (usually sponsor)
Trial design:
- Stopping rules
- IP accountability procedures
- Identification of source data
Sponsor Sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator:
- Against claims arising from the trial
- Except for claims that arise from malpractice and/or negligence
- Address the cost of treatment of trial subjects in the event of trial-related injuries
- Financial aspects should be documented in an agreement
The sponsor should not supply an investigator with the IP:
- Until the sponsor obtain all required documentation from MREC and NPCB
- Until all importation of clinical trial drugs go through customs even though a clinical trial import licence (CTIL) has been obtained.
CTIL and CTX Application
- Categories of product:
- Unregistered products when used or assembled (formulated or packaged) in a way different from the approved form for the purpose of clinical trial
- A traditional product with a marketing authorisation with indication for “traditionally used” when used for unapproved indication/therapeutic claims for clinical trial purpose
- Pharmacist required? Licence A for poisons/drugs (where applicable)
- NMRR registration number
- Approval from DCA, IEC/IRB
Monitoring
- “The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, SOPs, GCP and the applicable regulatory requirements.” ICH GCP 1.38
Audit
- “A systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were recorded, analyzed and accurately reported, according to the protocol, sponsor’s SOPs, GCP and the applicable regulatory requirements.” ICH GCP 1.6
Inspection
- “The act by regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor’s and/or Contract Research Organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the regulatory authority(ies).”
By the end of the workshop, we have to sit for certification examination. The exam consist of 40 Multiple Choice Questions (MCQs) but we have to choose the best answer within 1 hour.
Best of luck!
It’s all about patient’s safety and data integrity.
“Sesungguhnya di sisi Allah ilmu tentang hari kiamat; dan Dia yang menurukan hujan dan yang mengetahui apa yang ada di dalam rahim. Dan tiada seorang pun yang dapat mengetahui (dengan pasti) apa yang akan dikerjakan esok. Dan tidak ada seorang pun yang dapat mengetahui bumi mana dia akan mati. Sesungguhnya, Allah Maha Mengetahui, lagi amat meliputi pengetahuan-Nya.”
(Surah Luqman 31: 34)
Until we meet again.
May peace be upon you.
Hera Syahirah ヅ 