A brief awareness presentation about Oncology Clinical Trials and how the current regulatory scenario is affecting it. The oncology patients are the greatest losers.

1. 1
Oncology Clinical Trials-
Regulations & Benefits
Dr.Harsha Doddihal
Associate Medical Director
Quintiles
Disclaimer: The views expressed here are in personal capacity and
do not represent that of Quintiles.

2. 2
Objective
• Understanding Regulatory Scenario in India
• How this affects Oncology community and patients
• Brief Mention about Oncology Phase 1 and 2 trials
• Remarkable Story!
• Disclosure: Apart from being an Oncophysician, I also work as Associate
Medical Director at Quintiles an have the responsibility of working with
pharmaceutical companies, advising them on clinical research.

3. 3
Need For Regulations
• Moral & Ethical Challenges
International:
1. Nuremberg Code
2. Tuskegee Syphilis
Experiments
3. Beecher Article in NEJM
1966
4. Belmont Report
5. ICH-GCP 1990
http://www.hhs.gov/ohrp/archive/documents/BeecherArticle.pdf
http://www.wemos.nl/files/Documenten%20Informatief/Bestanden%20voor%20'Medicijnen'/examples_of_unethical_trials_feb_2008.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1121689/
National:
1. Letrozole Trial For Ovulation-2004
2. Streptokinase Trial-2003, 8 deaths
3. John Hopkins Scientist & RCC
Trivandrum-26 oral cancer pts
4. HPV Vaccine Trial-Khammam
district
5. Indore Story
Image Courtesy
http://crfocus.wordpress.com/tag/clinical-trials/

4. 4

5. 5
Regulations Today
• In the case of an injury occurring to the clinical trial subject, he or she shall
be given free medical management as long as required.
• Financial compensation above that of medical management
• Failure of investigational product to provide intended therapeutic
effect will be considered as trial related injury.
• Injury or death resulting due to placebo in a placebo controlled trial will be
considered as trial related and will require compensation.
• Adverse effects due to concomitant medication excluding standard care,
necessitated as part of approved protocol;
• Drugs and Cosmetics (First Amendment) Rules, 2013

6. 6
Impact On Oncology
39,767 studies listed on clinical trial site of US
526 studies listed on clinical trial site of India
No trials approved this year!

7. 7
Why Does It Matter?
• Patients are the greatest sufferers, being denied the chance, hope of
research therapy and paving way for future
• Personalized medicine demands need for local trials. Era of extrapolating
data will gradually change
• Lack of bio banks and local epidemiology, pathology data
• Academic studies have come to a halt
• Students facing problem in doing thesis
• WHO, NIH funded trials have been withdrawn or stalled
• MNCs and Indian companies are doing trials in other countries

8. 8
Phase 1 and Phase 2 in Oncology
• Phase 1 trials in Oncology are done in patients suffering from malignancy. In
other therapeutic areas phase 1 is done on healthy volunteers.
• Phase 2 Oncology trials can be randomized and accelerated to provide both
safety, efficacy results.
• Personalized Medicine requires more innovative thinking. We need better
trial designs, adaptive trials etc.

9. 9
An Inspiring Story
• An example….
At age 44 (1992) diagnosed of CML- Started on Hydroxyurea- only short duration
response
She received Busulphan-Not effective
Started on Interferon-alpha while being considered for Bone Marrow
1994- For Autologous BMT Stem cells were harvested at St Vincents Australia
With Interferon she did well and was on it from 1994 to 2000
2000- Decided to participate in Imatinib trial at Singapore
She went into accelerated phase on Imatinib in 2002 and received 3 cycles of
chemotherapy and received Imatinib again
2005- The resistance to Imatinib was full blown and she was found to have T315I
mutation. She also developed Parkinson in 2005
She did not fit for the Nilotinib trial in 2005
MK0457 a pahse1/2 trial for T315I mutation, they could not participate because of
logistic reasons
Imatinib dose increase did not help and she was put back on interferon, after 9
months she deteriorated
New trial of inject able drug called Omacetaxine- side effects of losing teeth, skin-
the intensity decreased
For 2 years she was on Omacetaxine before moving to a new trail involving
Ponatinib
She is doing well on Ponatinib

10. 10
An Inspiring Story
• An example….
At age 44 (1992) diagnosed of CML- Started on Hydroxyurea- only short duration
response
She received Busulphan-Not effective
Started on Interferon-alpha while being considered for Bone Marrow
1994- For Autologous BMT Stem cells were harvested at St Vincents Australia
With Interferon she did well and was on it from 1994 to 2000
2000- Decided to participate in Imatinib trial at Singapore
She went into accelerated phase on Imatinib in 2002 and received 3 cycles of
chemotherapy and received Imatinib again
2005- The resistance to Imatinib was full blown and she was found to have T315I
mutation. She also developed Parkinson in 2005
She did not fit for the Nilotinib trial in 2005
MK0457 a pahse1/2 trial for T315I mutation, they could not participate because of
logistic reasons
Imatinib dose increase did not help and she was put back on interferon, after 9
months she deteriorated
New trial of inject able drug called Omacetaxine- side effects of losing teeth, skin-
the intensity decreased
For 2 years she was on Omacetaxine before moving to a new trial involving
Ponatinib
She is doing well on Ponatinib

11. 11
• What can you do about it?
> Being aware helps patients, physician and society!
> Ignorance harms. Being aware of ethical concerns empowers and enhances. Allows
one to ensure adherence of guidelines and SOPs
> CDSCO invites people to comment on new rules and regulations!! We need to log
on to their site and provide our comments.
> Currently comments are being accepted for taking informed consent under video.
Thank You!!
Questions????
Curates Egg………Something good, something bad…….