moh clinical research approval process. dr. ahmad atif mirza

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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 Implicat Islmabad. Nov 7

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Page 1: 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

Page 2: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

REGULATORY STEPS OF NEW PRESCRIPTION DRUGS

RARA

Page 3: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 4: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

Good Clinical Practice

“Regulations tell you what you are required to do by law.”

“Guidelines tell you the best way to do it”

Page 5: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

What Is GCP Anyway?

GCP = Good Clinical Practices

This may mean a variety of things to different people…

Page 6: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 7: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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.

Page 8: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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.

Page 9: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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.

Page 10: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 11: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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)

Page 12: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 13: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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.

Page 14: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 15: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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?

Page 16: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 17: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

Protecting Participants Before a Trial

Scientific review by sponsoring organization

Institutional review board approval

Informed consent

Page 18: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 19: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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.

Page 20: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 21: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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"

Page 22: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 23: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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):

Page 24: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 25: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 26: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

REGULATORY STEPS OF NEW PRESCRIPTION DRUGS

RARA

Page 27: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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

Page 28: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza
Page 29: MOH Clinical Research Approval Process. Dr. Ahmad Atif Mirza

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