MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza
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Transcript of MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza
MOH clinical research approval process
Dr. Ahmad Atif Mirza MRCP
Medical and RnD Director, Highnoon Laboratories Ltd., Lahore
President, Pakistan Association of Pharmaceutical Physicians
Bahria/HEC Workshop on CR in Life Sciences and the Industrial ImplicationsIslmabad. Nov 7 2007
REGULATORY STEPS OF NEW PRESCRIPTION DRUGS
RARA
Ministry of Health, Drug Control office
(MOH-DC) rules and regulations regarding:
Standards to protect rights of clinical trial subjects
Standards to assure accuracy & credibility of data & reported results
Good Clinical Practice
“Regulations tell you what you are required to do by law.”
“Guidelines tell you the best way to do it”
What Is GCP Anyway?
GCP = Good Clinical Practices
This may mean a variety of things to different people…
What Is GCP Anyway?
To a physician GCP is following accepted standards of care for a specific disease process
To a nurse, GCP is giving good patient care according to nursing standards of care
To a principal investigator GCP is following the rules and regulations set forth by the RA/MOH and ICH to govern clinical trials
Definition
Word “clinical” is derived from the Greek kline which means bed so the term seems to be related to the “bedside” aspect of the patient/physician relationship.
A clinical trial is a type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease.
Features of well-designed clinical trials
Clearly stated objectives.
Well-defined endpoints or quantifiable measures derived from these objectives.
A priori stated decision rules for success or failure of the experimental treatment based on statistical tests involving these endpoints.
When necessary, a clearly presented calculation of the sample size and its associated power.
Well-described patient inclusion and exclusion criteria, and patient screening and randomization.
Features of well-designed clinical trials
A system of data monitoring; this includes: Safety and efficacy monitoring, possibly by an external
body (e.g., a Data Safety Monitoring Board or DSMB), with possibly explicit rules for early study termination.
Data quality monitoring and error correction.
All examinations, tests, and evaluations described in detail along with a schedule of when they are to be performed.
A data collection system which is based on data collection instruments called Case Report Forms (CRFs) as well as a system of digital data entry.
Why Do Clinical Trials?
Evidence-based medicine era Objectivity
Scientific documentation
Positive significance and relevance
Negative significance
Evidence-based Medicine Finding, analyzing, disseminating and using the very best
scientific evidence in combination with clinical expertise to
treat patients
Study Design in Clinical Research
“There are only a handful of ways
to do a study properly but a
thousand ways to do it wrong.”
Sackett (1986)
Some Fundamental Points
No research study stands alone; it must be evaluated along with all available evidence from lab, animal, and other clinical studies.
Be careful of over-interpreting results; ASSOCIATION CAUSATION
The “best” statistical analysis is only as good as the data it’s based on.
Continued
Fundamental Points
Flaws in research design are common, and, when present, can completely invalidate the results of any study.
A well-designed, properly conducted, randomized clinical trial provides the clearest, most definitive evidence regarding the effectiveness of an intervention.
The Drug Development and Approval Process
1. Early research and preclinical testing
2. IND application filed with RA
3. Clinical trials (phases 1, 2, and 3)
4. NDA filed with RA
5. RA validates claim and approves drug
Phases of Clinical Trials
Phase 1: 15-30 people What dosage is safe? How should treatment be given? How does treatment affect the body? (ADME)
Phase 2: Less than 100 people Does treatment do what it is supposed to? How does treatment affect the body?
Phases of Clinical Trials
Phase 3: From 100 to thousands of people Compare new treatment with current standard
Phase 4: From hundreds to thousands of people Usually takes place after drug is approved Used to further evaluate long-term safety and
effectiveness of new treatment
Protecting Participants Before a Trial
Scientific review by sponsoring organization
Institutional review board approval
Informed consent
Protecting Participants During a Clinical Trial
Institutional review boards (IRBs)
Data and safety monitoring boards (DSMBs) Minimize risks Ensure integrity of data Can stop study if necessary
Ethics
Autonomy (right of patients for self-governance)To exercise this right, a patient must be informed on the benefits and potential risks of the new treatment/procedure (related to the requirement of obtaining informed consent from patients).
Beneficence is the patient’s right to be benefited from therapy, and the physician’s duty not to harm the patient.
Justice or fairness of distribution of the burdens and benefits of the research. For example, testing on poor people or minorities, and then distributing to the privileged would be in direct violation of this principle.
Ethical Norms of Clinical Trials
Sound study designs take into account:
Randomization or sharing of risks
Proper use of placebo
Processes to monitor safety of rx/tx
Competent investigators
Informed consent
Equitable selection of participants
Compensation for study related injuries
Ethical Issues: Protection of Human Subjects
Rely on integrity of Investigator but outside groups also have oversightParticipants’ rights protected by Institutional Review Boards [IRBs]
o An IRB is defined as: "any board, committee or other group formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of biomedical research involving human subjects"
Human Subjects’ Protection
IRB responsible for such tasks: IRB responsible for such tasks:
Review research to ensure that potential benefits outweigh risksDevelop and issue written procedures
Review research for risk/benefit analysis & proper protection of subjects
Issue written notice of approval/disapproval to the Investigator
Review and respond to proposed protocol changes submitted by the Investigator
Human Subjects’ Protection
Review reports of deaths, and serious and unexpected adverse events received from the InvestigatorConduct periodic continuing review of the study, study risks, selection of subjects, privacy of subjects, confidentiality of data, and the consent process
IRB Responsibilities (continued):
Informed Consent:A Part of Human Subject Protection
Objectives of Informed Consent
To Ensure: Voluntariness Comprehension Information
To Demonstrate That: Person freely gave consent to participate Consent given by a competent person Person has been given all information Person knows this is research – not treatment
Components of Informed Consent
Must Include the Following Information:• Why research being done?• What researchers want to accomplish• What will be done and for how long• Risks & benefits of trial• Other treatments available• Can withdraw from trial whenever desire• Compensation for unexpected injuries
REGULATORY STEPS OF NEW PRESCRIPTION DRUGS
RARA
Investigator Brochure
Final Protocol
Informed Consent (English and Urdu)
COA
List of Participating Countries
Sample of Label
Quantity of import on Form 4 along with the sites where trials to be conducted
CV's of Investigators
Ethics Committee Approval of Sites
GMP Certificate along with the CPP/FSC of COO in case of Phase IV trials.
Pre clinical / Clinical data
Summary of the Protocol
Summary of the IB ( for quick review on drug).
MOH Check List
Ethics of Clinical Trials: Protection of Participants
3 ethical principles guide clinical research:
Respect for Persons:: Treatment of person as autonomous
Beneficence:: Issue re: potential conflict between good of society vs. individual
Justice:: Treatment of all fairly & all equally share benefits & risks