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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.

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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.

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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/

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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

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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!

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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

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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.

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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

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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

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• 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…….