Recap: 18 Dec 2014

Current Regulatory Requirements for Members of Institutional Ethics Committee

Evolution of Guidelines • Tuskegee Syphilis Study, Nazi Medical Experiments, The Tearoom Sex

Study, HPV study, Indore study • Nuremberg Code, Bioethics Policy – U.S.: Research on the Fetus, Research Involving Prisoners, Research Involving Children, Institutional Review Boards, The Belmont Report: Principle Application

Autonomy: Respect for persons • Individuals should be treated as autonomous agents • Persons with diminished autonomy are entitled to

protection.

Informed consent • Subjects, to the degree that they are capable, must be

given the opportunity to choose what shall or shall not happen to them

• The consent process must include three elements: • Information, • Comprehension, and • Voluntariness.

Beneficence • Human subjects should not be harmed • Research should maximize possible benefits and minimize

possible harms.

Assessment of risks and benefits • The nature and scope of risks and benefits must be

assessed in a systematic manner

Justice • The benefits and risks of research must be distributed fairly.

Selection of subjects • There must be fair procedures and outcomes in the

selection of research subjects

Declaration of Helsinki 1964 – 2013

Recommendations guiding medical doctors in biomedical research involving human subjects.

– Duty of physician to protect the life, health, privacy and dignity of the human subject

– Review of proposed research by independent ethics committee – Medical research involving human subjects conducted by

scientifically qualified persons and under the supervision of a clinically competent medical person

– Physician to obtain the subject’s freely-given consent, preferably in writing

– Stress on publication of results - negative or positive

The International Conference on Harmonisation

Is unique in bringing together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration. (pioneered by EU, USA and Japan in 1990)

ICH E6: Based on a set of regulatory and ethics requirements, standards,

recommendations that apply to : Design, Conduct, Performance, Monitoring, Audit, Recording, Termination, Analysis and reporting of clinical trial

Cardinal Principles - Protection of Subject’s rights: To ensure that the rights, integrity and confidentiality of trial participants are protected - Data Integrity: To provide assurance that the data and reported results are credible and accurate

India Guidelines & Regulations

1956………: Code of Medical Ethics, MCI 2001: CDSCO GCP Guidelines 2003: revision of BE guidelines 2005: Revised Schedule Y 2006: Second revised ICMR ‘Ethical Guidelines for

Biomedical Research on Human Participants’ 2013: National Guidelines on Stem Cell Research

1. Essentiality 2. Voluntariness, informed

consent and community agreement (ECs shall decide about waiver)

3. Non-exploitation 4. Privacy and confidentiality 5. Precaution and risk

minimization

6. Professional competence 7. Accountability and

transparency 8. Maximization of the public

interest 9. Institutional arrangements 10. Public domain 11. Totality of responsibility 12. Compliance

ICMR Guidelines – General Principles

ICMR Guidelines – Specific Principles

• Clinical Trials of: Drugs, Devices, Vaccines, Diagnostic agents, Herbal Drugs

• Epidemiological Studies • Human Genetics Research • Transplantation Research including Fetal tissue and Xeno-

transplantation • Assisted Reproductive Technologies

The regulatory bodies accept that stem cell research is a nascent field, there are several elements of unpredictability in the translation of research outcomes: So ensure highest degree of scientific rigor and resolution of ethical concerns

2013 guidelines

Apply to – Research on human SCs and/or their derivatives – Basic as well as clinical research – And All type of SCs :Autologous/allogenic, Embryonic/fetal/adult, With

/without manipulation Institution shall maintain a registry of its investigators conducting stem cell

research and ensure that all registered users are kept up to date with changes in guidelines and regulations

Institution shall constitute an IC-SCR as per national stem cell guidelines

For monitoring of stem cell research and therapy: at the National level, National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT) which meets every 3 months or as often as required

Key Points Human clinical trials using stem cells must strictly adhere to

accepted principles: of Sch- Y, GCP Guidelines of CDSCO and Ethical Guidelines for Biomedical Research of ICMR

Approval and monitoring of clinical trials will take into consideration

the following factors but not limited to: Source and type of stem cells- adult, embryonic, fetal, iPSc etc. Autologous or allogeneic applications Degree of manipulation- minimal, more than minimal or major

At present, there are no approved indications for stem cell therapy other than the HSCT for hematological disorders. Accordingly, all SC therapy shall be treated as investigational and conducted only in the form of a ‘clinical trial’ after obtaining due regulatory approvals

Twin Pillars of Protection

• Independent Review • Informed Consent

ETHICS COMMITTEE

Basic Responsibility: To protect the dignity, rights and well being of potential research participants. • Composition of Ethics Committee, • Roles and responsibilities of ECs • Overview of amendments 122 DD in Schedule Y: Changed

responsibilities of ECs due to these changes

CDSCO Requirements

• Compulsory registration with CDSCO of all ECs reviewing regulatory clinical trials to approve Clinical Trials or BA/BE studies in India : – Initial registration of all ECs is granted for 3 YEARS by DCGI – Any change in the EC members should be notified to DCGI – Registration of ECs in accordance with requirements of Appendices

VIII of Schedule Y

• ECs will allow CDSCO to inspect/ verify its records. • Maintain all documents for audit/inspection by DCGI

Changed Responsibilities

Registered ECs have to analyze SAE and forward its opinion to DCGI (As per newly added appendix XII)

Registered ECs to Carry ongoing review of such studies

Records to be maintained by EC

• Composition of EC • CV of all EC members • SOPs • National and International guidelines • Copy of CRF, IB, protocol, data collection formats, etc. • Agenda and minutes of all EC meetings (Sign of chairperson

on each page of minutes)

Records to be maintained by EC

• Copy of all communication with EC members and PI (regarding application, decision and follow-up)

• All notifications for suspend/termination of a study with reasons

• Final report of the study (microfilms, CD or any video recording etc.)

• Time of record maintenance - Min 5 yrs from the date of termination of a study (both in hard and soft copy)

Administration & Management • Full time secretariat & space for records – well functioning

IEC. • Members – reasonable compensation for reviewing

proposals. • Reasonable fees charged – expenses related for review &

administrative processes. • Institutions allocate reasonable funds – smooth functioning

of IEC.

Informed Consent • A process of shared decision making by the physician and

patient • An active communicative process • Any trial related procedure will begin only after the

written informed consent is obtained • General Elements of Informed Consent

CENTRAL DRUGS STANDARD CONTROL ORGANIZATION DIRECTOR GENERAL OF HEALTH SERVICES,

Ranjit Roy Chaudhary Report 2013

Recommendations of Prof. Ranjit Roy Chaudhury Expert Committee to Formulate Policy and Guidelines for Approval of :

1. Clinical Evaluation of New Drugs 2. Approval of Drugs 3. Post-marketing Surveillance 4. Banning of Drug 5. Strengthening of CDSCO

Regulations (Sch Y) Updates

• DCGI Order dated 3 Jul 2014 – Sponsor to provide compensation to the trial participant/

nominee, if any drug-related anomaly is discerned at a later stage and accepted to be drug related injury or death

– Sponsor to provide ancillary care to the subject for brief illness in the same hospital/ trial site, wherever required

Regulations (Sch Y) Updates

• DCGI Order dated 3 Jul 2014 – Academic clinical research may be approved by IEC. – However, if a new drug is being evaluated or a new use

for an existing drug is being evaluated, then approval of DCGI is needed

Regulations (Sch Y) Updates

• DCGI Notice dated 30 Jul 2013 – Independent EC shall review and approve only the study

protocol of BA-BE studies of the approved drug – Carry ongoing review of such studies – No new CT shall be reviewed and approved by

Independent CT registered for conducting BA-BE studies

Regulations (Sch Y) Updates • Drugs and Cosmetics (2nd Amendment) Draft Rules, 2013 – 7

Jun 2013 – Sch Y Appendix V (ICF): Additional Info to be added (Trial

Participant Details) • Address • Qualification and Occupation • Annual income of the subject • Name & address of his nominee

– Mandatory for Investigator to hand over a copy of duly filled ICD to the subject or his/her attendant

Regulations (Sch Y) Updates • Drugs and Cosmetics (Amendment) Bill, 2013 has been

introduced in the Parliament on 29 Aug 2013. The Bill contains a separate chapter on clinical trials containing penal provisions, provisions for payment of compensation, Ethics Committees, etc.

ICMR

• Increased transparency,

accountability and accessibility

of clinical trials.

• Curtailed inadequate reporting

of trials

• Made public and regulatory

bodies acquainted with current

clinical trials going on in India.