Regulatory changes in clinical trials

An overview of the regulatory changes in the clinical trial landscape in India across the years.

1. September the 17
th
2014
Wednesday,

2. 17 September 2014 Department of Pharmacology, KMC, Manipal2
The Big PharmaExpose!

3. Moderator
Dr Chaithanya MalalurDr Smita Shenoy
Presenter
Department of Pharmacology, KMC, Manipal

4. 17 September 2014 Department of Pharmacology, KMC, Manipal4
Protocol

5. 17 September 2014 Department of Pharmacology, KMC, Manipal5
Current scenario
Of total cost of
developing a
molecule as a
drug is due to
clinical research
India –preferred
avenues for CT
related activities
of global share
Additional research
personnel
(investigators,
auditors, EC
members & data
safety managers)
-Planning
commission report

6. 17 September 2014 Department of Pharmacology, KMC, Manipal6
Factors favouring
Nearly ½the operational cost
Low per patient trial cost
Large number of well trained, qualified English speaking
professionals
Large pool of patients
Diverse ethnic subjects
Wide variations of diseases
Numerous Govt. Med. Colleges, institutions, labs with state-of-the-
art facilities
Aa

7. 17 September 2014 Department of Pharmacology, KMC, Manipal7
Drawbacks
This trend is leading to more cases of
inadequate Informed Consent and unethical
treatment of human subjects
ICF analyzed
Deviate from
requirements
of the law

8. 17 September 2014 Department of Pharmacology, KMC, Manipal8
Milestones
In the landscape of Drug
Regulations in India
1927 1947 1958 1970 1994 2005 2006 2007 2009 2011 2013 2014

9. 17 September 2014 Department of Pharmacology, KMC, Manipal9
“Gigantic quinine fraud”
1920-30 reports of harmful substitutes and
adulterants were identified to be marketed in
place of genuine drugs.
No control over the manufacturing sale and
distribution of drugs
-Indian Medical gazette
Sir Haroon Zaffer(March 9, 1927) recommended
to the Governor General
“To take immediate steps to control the craze of
medicinal drugs by, legislation-for-standardization
of preparation and sale, of such drugs."
“Drugs enquiry committee” constituted under the
chairmanship of Col. R. N. Chopra
1.To enquire & check the quality of drugs, that
are being imported, manufactured and sold.
2.To suggest remedial measures in preventing
adulteration
oReport submitted in 1931
o1937 ‘The drug bill’
o1940 amended to ‘The drugs act’
o1945 Drugs and Cosmetics rules
o1947 April 1
st
Drugs & Cosmetics Act came
into effect

10. 17 September 2014 Department of Pharmacology, KMC, Manipal10
Drugs and Cosmetics act
Chapter 2
Drugs Technical Advisory Board (DTAB)
Drug Consultative Committee (DCC)
separately for
Modern Scientific System of Medicine
Indian traditional system of Medicine
Central Drug Laboratory at Central
Research Institute, Kasauli

11. 17 September 2014 Department of Pharmacology, KMC, Manipal11
Hon. RajagopalaAyyangerCommittee report
The Indian Patents Act of 1970
Had provisions for ‘process’ patents only
Most industry did not flourish except the generics industry
Western firms -apprehensive to introduce their new innovative product

12. 17 September 2014 Department of Pharmacology, KMC, Manipal12
1994 Government signed the agreement on
Trade Related Aspects of Intellectual
Properties (TRIPS)
Minimum protection to the I.P by the member
states of World Trade Organization (WTO)
2005 amendment -strong TRIPS competent
‘Product’ patent system for pharmaceutical
products

13. 17 September 2014 Department of Pharmacology, KMC, Manipal13
By The Indian Council of Medical Research (ICMR)
Ethical guidelines for biomedical
research on human subjects
2001 -CDSCO released Indian Good Clinical
Practice (GCP) guidelines

14. 17 September 2014 Department of Pharmacology, KMC, Manipal14
No regulatory requirement for GCP compliance → most
companies did not invest in clinical trials
Low quality data resulted in worsening India’s
reputation
India’s strict bureaucratic system → delay in obtaining
customs clearance for equipment and IP
Shortcomings

15. 17 September 2014 Department of Pharmacology, KMC, Manipal15
CDSCO made drastic revisions to Schedule Yto try to
bring it on at par with internationally accepted
definitions and procedures
Definitions for Phase I-IV trials, which eliminated the Phase lag
Clear responsibilitiesfor investigators and sponsors
Requirements for notifying changesin protocol.

16. 17 September 2014 Department of Pharmacology, KMC, Manipal16
Schedule Y
Requirements and guidelines for permission to import
and/or manufacture of new drugs for sale or to
undertake clinical trials
to adopt more sophisticated regulations to better
protect their citizens
to invite more industry
to ensuring that the data from India is more
acceptable internationally

17. 17 September 2014 Department of Pharmacology, KMC, Manipal17
Structure of schedule Y
Application for permission Clinical Trial
Conduct of clinical trial
Responsibilities of Sponsor & Investigator(s)
Ethics Committee
Informed Consent
Phases of clinical trial
Studies in special populations:
oGeriatrics
oPaediatrics
oPregnant or nursing women
Post Marketing Surveillance-Periodic Safety
Update Reports
Special studies: Bioavailability / Bioequivalence
Studies
Appendix I to XI

18. 17 September 2014 Department of Pharmacology, KMC, Manipal18
Older Schedule Y ( 1988) Amended Schedule Y (2005)
Narrow and restrictive definitions of clinical
trial phases .
Provide pragmatic definition of all phases
Restriction on number of patients and
centers in early phasesof trials
No such restriction , depend on protocol
requirements
Details of Informed consent Form was not
given
Details of Informed consent Form is given .
Ethical committee responsibility not
mentioned
Responsibilities of ethical committee
mentioned.
Postmarketing study (Phase 4 ) not
mentioned.
Postmarketing study (Phase 4 ) mentioned.
Guidelines for Studies in special populations
not given.
Guidelines for Studies in special populations
given .e.g. geriatric , child, pregnant etc.

19. 17 September 2014 Department of Pharmacology, KMC, Manipal19
Phases of CT
Phase I
Safety & tolerability, pharmacokinetic & pharmacodynamics
study
Phase II
Dosing –efficacy (therapeutic exploratory trial –few patients)
Phase III
Efficacy compared to gold standard (therapeutic confirmatory
trial –more patients)
Phase IV
Post marketing surveillance (pharmacovigilance)

20. Created two categories of applications
Category A
Category B
17 September 2014 Department of Pharmacology, KMC, Manipal20
Fast tracking of
clinical trials
To decrease the review time of
application from 16 weeks to 10 weeks

21. 17 September 2014 Department of Pharmacology, KMC, Manipal21
Service tax on
clinical trial was
cancelled
was removed to
get samples out
of India

22. subjects who suffer physical injury
as a result of their participation
→ financial or other assistance
subject to confirmation from IEC
Death → compensation to
dependents
17 September 2014 Department of Pharmacology, KMC, Manipal22
Registration
contracted by the sponsor to
carry out any or all obligations,
shall perform such functions
only, if it is duly registered to
Licensing Authority

23. 17 September 2014 Department of Pharmacology, KMC, Manipal23
Incentives
Boost to pharma industry
Questionable ethics
?
2009 2012

24. 17 September 2014 Department of Pharmacology, KMC, Manipal24
of Parliamentary Standing Committee on
Health & Family Welfare
oThe Committee is of the firm opinion that most of the ills
besetting the system of drugs regulation in India are mainly
due to the skewed priorities and perceptions of CDSCO.
oFor decades together it has been according to the
propagation and facilitation of the drugs industry, due to
which, unfortunately, the interest of the biggest stakeholder
i.e. the consumer has never been ensured.
oTaking strong exception to this continued neglect of the poor
and hapless patient, the Committee recommends that the
Mission Statement of CDSCO be formulated forthwith to
convey in very unambiguous terms that the organization is
solely meant for public health.

25. 17 September 2014 Department of Pharmacology, KMC, Manipal25
drugs picked up
randomly for scrutiny
Ministry could not provide any
documents on the grounds that
files were non-traceable
pefloxacin
lomefloxacin
sparfloxacin

26. 17 September 2014 Department of Pharmacology, KMC, Manipal26
drugs Phase III clinical trials mandated
by Rules were not conducted
2 drugs CT conducted on just
patients respectively as against the
statutory requirement of at least
1 drug: trials were
conducted at just
legal requirement
of 3-4 sites
did not have permission for sale in

27. 17 September 2014 Department of Pharmacology, KMC, Manipal27
Regulatory bodiesinvolved in drug regulation
CDSCO Regulatory body governed by Directorate General of
Health Services of MoHFW
DCGI Assess the quality, safety and
efficacy of a drug
ICMR Apex body -formulates, co-ordinates and
promotes biomedical research
GEAC Clinical trials involving
the use of biotech products
DCC Technical guidance to CDSCO
CDL National statutory laboratory of the Indian government for
quality control of drugs
DTAB Technical guidance to the CDSCO

28. 17 September 2014 Department of Pharmacology, KMC, Manipal28
Ministry of Health and Family Welfare -public health
Ministry of Chemicals and Fertilizers -Industrial policy
Ministry of Environment and Forests
Ministry of Finance
Ministry of Commerce and Industry
Ministry of Science and Technology
Department of Industrial Policy and Promotion -Regulation of
Patents
Directorate General of Foreign Trade under the aegis of
Ministry of Commerce and Industry -drug exports
CDSCO, MoHand FW -Licensing and quality control and
distribution
Department of Biotechnology, Ministry of Science and
Technology
Ministry/Department concerned with drug regulation

29. 17 September 2014 Department of Pharmacology, KMC, Manipal30
Clinical Trials regulated by
Rule 122 A to E of D&C act
Schedule Y of D&C act and the rules there under
GCP guidelines issued in 2001
Ethical guidelines for biomedical research of human subjects by ICMR

30. 17 September 2014 Department of Pharmacology, KMC, Manipal31
Amendments to Schedule Y
Drugs and Cosmetics (First Amendment) Rules 30
th
January 2013
Drugs and Cosmetics (Second Amendment) Rules 1
st
February 2013
Drugs and Cosmetics (Third Amendment) Rules 8
th
February 2013

31. 17 September 2014 Department of Pharmacology, KMC, Manipal32
First Amendment
Reporting SAE
timelines
30
th
January 2013
Compensation for
trial related injury
Responsibilities of
Sponsor, Investigator
& Ethics committee
#1 #2 #3

32. 17 September 2014 Department of Pharmacology, KMC, Manipal33
122 DAB of Schedule Y
Any injury occurring to a clinical trial subject
→ Sponsor to provide free medical management
as long as required
Clinical trial related injury to a trial subject
→ Sponsor to provide free medical management
as long as required + $$$
Clinical trial related death
→ Sponsor to provide financial compensation to
the nominee + cost of medical management (if any)

33. 17 September 2014 Department of Pharmacology, KMC, Manipal34
Any injury or death
to a clinical trial
subject due to the
following reasons
shall be considered
as clinical trial
related injury or
death
Adverse effect of IP
Violation of the approved protocol,
scientific misconduct/negligence by
sponsor/investigator
Failure of IP to provide intended therapeutic
effect
Adverse effects due to concomitant
medication as part of protocol excluding
standard care
Injury to a child in-utero because of the
participation of parent in CT
Any procedure involved in the study

34. 17 September 2014 Department of Pharmacology, KMC, Manipal35
In case sponsor fails to provide
medical managementfor the
injury to the subject and/or
financial compensationfor trial
related injury or financial
compensationto subject’s
nominee(s) in case of trial
related death, the licensing
authority may
provide opportunity to give in writing why
such an order could not be passed stating
reasons
cancel clinical trial
restrict sponsor/representative from
carrying out any further trials in the
country
any other action deemed fit under the
rules

35. 17 September 2014 Department of Pharmacology, KMC, Manipal36
B = Base amount (i.e. 8 lacs)
F = Factor depending on the age of the subject as per Annexure 1 (based
on Workmen Compensation Act)
R = Risk Factor depending on the seriousness and severity of the disease,
presence of co-morbidity and duration of disease of the subject at the time
of enrolment in the clinical trial between a scale of 0.5 to 4
Formula by Independent Expert Committee for
quantum of compensation in case of SAE of death
Compensation = (B x F x R)/ 99.37

36. 17 September 2014 Department of Pharmacology, KMC, Manipal37
Example
The formula leads to compensation
amounts ranging from Rs.4,00,000 for
the death of a 65 year old
terminally ill subject with expected
survival of less than six months to Rs
7.3m for the death of a 16 year old
healthy volunteer.

37. 17 September 2014 Department of Pharmacology, KMC, Manipal39
sponsor
SAE
SAE
death
EC ExC
LA HoI
EC
LA HoI
of

38. 17 September 2014 Department of Pharmacology, KMC, Manipal40
of
Premature termination: submit summary report along
with reason for termination
Quality assurance
adopt GCP guidelines
Trial status
reporting to licensing authority annually

39. 17 September 2014 Department of Pharmacology, KMC, Manipal41
SAEdeath
EC
{ }
Investigator
of

40. 17 September 2014 Department of Pharmacology, KMC, Manipal42
of
Management of all ADR / AE
Adhereto approved protocol
and GCP guidelines
Document all SOPs

41. 17 September 2014 Department of Pharmacology, KMC, Manipal43
ExC
SAEdeath{ }
of
EC
Report +
Opinion on
compensation
LA

42. 17 September 2014 Department of Pharmacology, KMC, Manipal44
If EC revokesapproval of a study
oRecord reasons for the same
oInform investigator and Licensing Authorities
immediately
Safeguardrights, safety and wellbeing of
research participants
Protectvulnerable subjects
Obtain and maintain record of SOPs
Ongoing review based on periodic
progress reports

43. 17 September 2014 Department of Pharmacology, KMC, Manipal45
LA shall determine the cause of death based on
the recommendation of the Expert committee
and pass orders as deemed necessary
LA shall also decide the quantum
of compensationto be paid by
the Sponsor and pass orders
of
The sponsor shall pay the compensation
in case of a trial related injury / death
as per the Licensing authority within
of receipt of
such an order

44. 17 September 2014 Department of Pharmacology, KMC, Manipal46
Informed Consent form
The three corner stones

45. 17 September 2014 Department of Pharmacology, KMC, Manipal47
Involves research+ purpose
Expected duration
Description of the procedures
Reasonable foreseeable risks or discomforts
Expected benefitsto the subject or others (no
benefit?)
Specific appropriate, alternativeprocedures or
therapies available
Confidentialityof the records + who will have
access to the subject’s medical records
Informed
Consent form
Mandatory elements
specified under
Schedule Y

46. 17 September 2014 Department of Pharmacology, KMC, Manipal48
Treatment schedule(s)+ randomassignment (for RCTs)
Compensation and/or treatment(s)available to the subject in the
event of a trial-related injury
whom to contactfor trial-related queries, rights of subjects and in
the event of any injury
payment, if any
Subject’s responsibilities
participation is voluntary+ can withdraw at any time and that
refusal to participate will not involve any penalty or loss of benefits
to which the subject is otherwise entitled
Informed
Consent form
Mandatory elements
specified under
Schedule Y

47. 17 September 2014 Department of Pharmacology, KMC, Manipal49
Subject’s participation may be terminatedby the investigator without the
subject’s consent
Additional coststo the subject that may result from participation
Consequencesof subject’s decision to withdraw + procedures for orderly
termination of participation by subject
Notification of significant new findingsduring the course of the research which
may affect the subject’s willingness to continue participation
A statement that the particular treatment or procedure may involve risksto the
subject (or to the embryo or foetus, if the subject is or may become pregnant),
which are currently unforeseeable.
Approximate numberof subjects enrolled in the study.
Informed
Consent form
Mandatory elements
specified under
Schedule Y

48. 17 September 2014 Department of Pharmacology, KMC, Manipal50
Informed
Consent form
Percentage of ICFs in
disagreement with
elements in Schedule Y
0
10%
00
8%
30%
00
2%2%2%2%
26%
8%
4%4%
14%
8%
6%
0
5
10
15
20
25
30
35
ABCDEFGH IJKLMNOPQRS
% of ICF deviating
Points in schedule Y
Failed to mention specific
appropriate, alternative
procedures or therapies
available
Failed to mention participation is
voluntary+ can withdraw at any time
Failed to mention about notification
of significant new findings

49. 17 September 2014 Department of Pharmacology, KMC, Manipal51
Informed
Consent form
Changes in Schedule Y -
Appendix V (Informed consent)
In the event of an injury occurring in the
clinical trial, such subject will be provided free
medical management as long as required
In the event of trial related injury or death, the
sponsor shall provide medical management and
financial compensation for the injury or death

50. 17 September 2014 Department of Pharmacology, KMC, Manipal52
A Serious Adverse Event is an untoward medical
occurrence during a clinical trial that is associated with
Death
In-patient hospitalization (in case study was conducted on
an out-patient)
Prolongation of hospitalization (in case study was conducted
on an in-patient)
Persistent or significant disability or incapacity
Congenital anomaly or birth defect
Is otherwise life-threatening

51. 17 September 2014 Department of Pharmacology, KMC, Manipal53
Adverse effect of investigational product
Violation of the approved protocol, scientific misconduct or
negligence by the sponsor or investigator
Failure of investigational product to provide intended
therapeutic effect
Use of placebo in a placebo controlled trial
Adverse effects due to concomitant drug, excluding
standard care, used as part of approved protocol
Injury to a child in utero because of the parent’s
participation in a clinical trial
Any clinical trial procedures involved in the study
Conditions attributable to clinical trial injury or death

52. 17 September 2014 Department of Pharmacology, KMC, Manipal54
Second Amendment
1
st
February 2013
Licensing Authority shall grant
permission to conduct clinical trial if
following criteria are met
CT -conducted in according to the approved protocol,
conforming to Schedule Y requirements and GCP guidelines
Approval of Ethics committee should be taken before
starting the trial
CT shall be registered with The Clinical Trials Registry India
(CTRI) before enrolling the 1
st
patient.
Annual status report of trial (whether continued or
terminated) should be submitted to the LA. If trial was
terminated, the reasons for doing so should be stated
Any report of SAE shall be forwarded within 10 working days
as per Schedule Y requirement

53. 17 September 2014 Department of Pharmacology, KMC, Manipal57
Second Amendment
1
st
February 2013122DAC

54. 17 September 2014 Department of Pharmacology, KMC, Manipal58
Mandates the registrationof Ethics Committee
In case of SAEthe Ethics committee shall, analyze and
forward its opinion as per procedure in Appendix XII of
schedule Y
To be subject to scrutiny and inspectionby the CDSCO
(data, documentation of clinical trials)
The registration unless cancelled or suspended shall remain
valid for a period of 3 years
The Ethics committee shall have a minimum of 7 members.
Members should be conversant with GCP guidelines.

55. 17 September 2014 Department of Pharmacology, KMC, Manipal59
For review of each protocol the quorum of
Ethics Committee should be at least
members with the following representations

56. 17 September 2014 Department of Pharmacology, KMC, Manipal60
New committees set up
An apex committee under the
Chairmanship of Sec. of H&FW
to take stock of new approvals and
to supervise and monitor the
conduct of the clinical trial in the
country
A Technical Committee
to give inputs to Apex
Committee
For supervising the
clinical trials on new
chemical entities
Expert Committee
to formulate policy guidelines and SOPs for
approval of new drugs, clinical trials &
banning of drugs
The Expert Committee
formulate policy guidelines and procedures
for approval of fixed dose combinations
Two Expert
Committees

57. 17 September 2014 Department of Pharmacology, KMC, Manipal61
Audio-video recording of consent
Informationfor prospective study subject (ICF format)
Privacy & confidentiality(videographer should
be engaged as part of the study team)
Consentof the subjects for audio-visual recording (documented )
Procedureof audio-visual recording (Identify the protocol, the
subject/LAR and the language)
Qualityof A-V recording
Storage & archivalof audio-visual recordings(at least 5 years)
Draft guidelines (16
th
January 2014)

58. 17 September 2014 Department of Pharmacology, KMC, Manipal62
Shortcomings
The newer 2013 regulations was criticized as
particularly harsh towards the industry

59. 17 September 2014 Department of Pharmacology, KMC, Manipal63
Shortcomings
Regulatory approval process is slow → new requirements for submission and
review of the CT
No. of investigator sites has reduced as only registered EC can approve CT
protocols
Increasingly difficult to convince the investigators to conduct CT
Anxiety and fear amongst the potential patients
Pts may be unwilling to undergo (AV) recording of the consent process
↑Per-pt-cost → ↑drug cost
Rules very generous toward subjects –compensation: alternative to insurance in
terminally ill subjects
Sponsor has to bear the burden of even investigator’s negligence or misconduct

60. 17 September 2014 Department of Pharmacology, KMC, Manipal64
Critical Analysis
Unintended consequences for public health research
International collaborative
research projects
suspended
mil

61. 17 September 2014 Department of Pharmacology, KMC, Manipal65
Critical Analysis
Failure of investigational product to provide
intended therapeutic benefit
Use of placebo in a placebo controlled trial
Adverse effects due to concomitant medication,
excluding standard care
Questions the fundamental science of
testing a research hypothesis
Double edged sword (failure of IP/no
benefit with placebo) (lose-lose)
Placebo is the only way of assessing
whether the IP is associated with
undue risk or significant benefit

62. 17 September 2014 Department of Pharmacology, KMC, Manipal66
Prof. Ranjit Roy Chaudhury Expert Committee
to formulate policy and guidelines for approval of
new drugs, clinical trials and banning of drugs
To recommend changes and
introduce measures
To make the drug Regulatory
System for India more robust,
transparent and built on the
foundation of Science and Ethics
Vision
Methodology
Critical evaluation of the current system
In depth examination of the
parliamentary report and SC
judgements
Extensive Consultation with different
Stakeholders

63. 17 September 2014 Department of Pharmacology, KMC, Manipal67
Prof. Ranjit Roy Chaudhury Expert Committee
Central Accreditation Council to be established
Roster of experts from all over India and selection of experts by
random tables
Roster of accredited sites from which Pharma companies can select
Sites and PIs
Informed Consent from all participants. Audio-visual recording
wherever necessary in vulnerable groups
Response time from CDSCO –90 days

64. 17 September 2014 Department of Pharmacology, KMC, Manipal68
Prof. Ranjit Roy Chaudhury Expert Committee
No compensation for injury/death due to totally proven unrelated causes.
In all other cases compensation should be paid to the participant or his
legal heirs
No compensation for therapeutic inefficiency
Compensation Fund to be created at National, State or Institutional level
Drugs for only export and not for domestic use –BA/BE studies not
permitted
Upgrading of CDSCO with adequate strengthening and autonomy

65. 17 September 2014 Department of Pharmacology, KMC, Manipal69
Do over stringent regulations hamper research?
Rigid clauses on compensation → Decline in
investigator initiated research
Lack of awareness about trial regulations amongst
investigators may lead to legal hassles.
Academic researchhas also been severely hampered
due to strict regulations on clinical trials. Most students
are unable to carry out interventional researchand
get restricted to observational studies.

66. 17 September 2014 Department of Pharmacology, KMC, Manipal70
Will these changes improve the
quality of clinical trial conduct

67. KshirsagarN & Kumar V. Clinical pharmacology: Prospects and development in India.Indian
journal of pharmacology, (2011)43(5), p –489
Fifty-ninth report on the functioning of the central drugs
Standard control organisation (CDSCO) -RAJYA SABHA SECRETARIAT, NEW DELHI, RAJYA
SABHA SECRETARIAT, NEW DELHI
(http://164.100.47.5/newcommittee/reports/EnglishCommittees/Committee%20on%20Health%20
and%20Family%20Welfare/59.pdf)
-last accessed on 16.09.2014
Drugs and Cosmetics (First Amendment) Rules, 2013
-G.S.R. 53 (E) , 30
th
January 2013, Gazette of India, Extraordinary, Part II, section 3, sub-
section (i)
ACTIONS ON THE RECOMMENDATIONS OF PROF. RANJIT ROY
CHAUDHURY EXPERT COMMITTEE
(http://www.cdsco.nic.in/writereaddata/Action_RR_Choudhury_Committee__06.11.2013.pdf)
-last accessed on 16.09.2014
LeleR. D. How to ascertain drug related deaths during clinical trials?. The Journal of the
Association of Physicians of India, 61(10), (2013) P:33-737

68. P Barton; “The Great Quinine Fraud”: Legality Issues in the “Non-Narcotic” Drug Trade in British
India; Social History of Alcohol and Drugs, Volume 22, No 1 (Fall 2007)
Guidance for Industry on Submission of Clinical Trial Application for evaluating Safety and
Efficacy
(http://www.cdsco.nic.in/writereaddata/cdsco-guidanceforindustry.pdf)
-last accessed on 16.09.2014
Imran M, NajmiA K, Rashid M F, TabrezS, & Shah M A. Clinical research regulation in India-
history, development, initiatives, challenges and controversies: Still long way to go. Journal of
pharmacy & bioalliedsciences, 5(1), (2013) 2.
Bhatt A. Clinical trials in India: Way forward.
PerspectClinRes 2014;5:53-4.
DRAFT GUIDELINES ON AUDIO-VISUAL RECORDING OF INFORMED CONSENT PROCESS IN
CLINICAL TRIAL
(http://www.cdsco.nic.in/writereaddata/Guidance_for_AV%20Recording_09.January.14.pdf)
-last accessed on 16.09.2014
MudurG. Health activists attack Indian compensation formula for deaths attributed to
clinical trials. BMJ: British Medical Journal, (2013) P-347.

69. Shukla S. India's amended trials regulations spark research exodus. The Lancet, 382(9895),
(2013) P-845.
SugarmanJ, BhanA, Bollinger R, & Gupta A. India’s new policy to protect research
participants. BMJ: British Medical Journal, (2013) P347
MaitiR, & RaghavendraM. Clinical trials in India. Pharmacological Research, 56(1), (2007)
P1-10.
GhooiR. B. Injury and death in clinical trials and compensation: Rule 122 DAB. Perspectives in
clinical research, 4(4), (2013) P199.
KarwaM, Arora S, & Agrawal, S. G.. Recent Regulatory Amendment in Schedule Y: Impact on
Bioequivalence Studies Conducted In India. J BioequivAvailab, 5, (2013) P174-176.
Chatterjee S. Regulatory changes in conduct of clinical trials: A need for review. Indian
journal of pharmacology, 45(4), (2013) P-323.
KundapuraS. V, PoovaiahT & GhooiR. B. The big Cs of the informed consent form: compliance
and comprehension. Indian journal of medical ethics, (2013) p10
-The End
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