Prof K M Prasanna KumarSr prof & Head-Endocrinology &

DiabetesM S Ramaiah Medical college

Are people guinea pigs and mice? Men are not mice Efficacy Safety Ethnic and racial variations Pattern of clinical conditions/

management Reporting of unusual clinical situations Reporting of index case

A systematic study designed to evaluate a product (drug, device, or biologic) using human subjects, in the treatment, prevention, or diagnosis of a disease or condition, as determined by the product's benefits relative to its risks. Clinical investigations can only be conducted with the approval of the Food and Drug Administration (FDA)/DCGI

Any investigation in human subjects intended to determine the clinical pharmacological, pharmacokinetic, and/or other pharmacodynamic effects of an investigational agent, and/or to identify any adverse reactions to an investigational agent to assess the agent's safety and efficacy.

Study of drug, biologic or device in human subjects with the intent to discover potential beneficial effects and/or determine its safety and efficacy. Also called clinical study and clinical investigation. This does not encompass all the research that is carried out in the clinical setting (e.g., health services research).

Invitaion from sponsor Confidentiality agreement Review of protocol Site selection Investigator meeting IRB approval Site initiation Begin study

People participate in clinical research for a variety of reasons. People who volunteer for phase II and phase III trials can gain access to promising drugs long before these compounds are approved for the marketplace. They typically will get excellent care from the physicians during the course of the study. This care also may be free.

Contract Research Organization (CRO)

A person or an organization (commercial, academic or other) contracted by the sponsor to perform one or more of a sponsor's study-related duties and functions

Good Clinical Practice (GCP) International ethical and scientific quality

standard for designing, conducting, monitoring, recording, auditing, analyzing and reporting studies. Insures that the data reported is credible and accurate, and that subject's rights and confidentiality are protected.

Institutional Review Board (IRB) An independent group of professionals

designated to review and approve the clinical protocol, informed consent forms, study advertisements, and patient brochures, to ensure that the study is safe and effective for human participation. It is also the IRB's responsibility to ensure that the study adheres to the FDA‘/DCGI’s regulations.

Investigator A medical professional, usually a

physician but may also be a nurse, pharmacist or other health care professional, under whose direction an investigational drug is administered or dispensed. A principal investigator is responsible for the overall conduct of the clinical trial at his/her site.

Case Report Form (CRF)A record of pertinent information collected on each subject during a clinical trial, as outlined in the study protocol

A Phase One Study: Phase I studies are primarily concerned

with assessing the drug's safety. This initial phase of testing in humans

is done in a small number of healthy volunteers (20 to 100), who are usually paid for participating in the study. The study is designed to determine what happens to the drug in the human body--how it is absorbed, metabolized, and excreted.

About 70 percent of experimental drugs pass this initial phase of testing.

Once a drug has been shown to be safe, it must be tested for efficacy. This second phase of testing may last from several months to two years, and involve up to several hundred patients.

One group of patients will receive the experimental drug, while a second "control" group will receive a standard treatment or placebo.

Often these studies are "blinded"--neither the patients nor the researchers know who is getting the experimental drug.

Only about one-third of experimental drugs successfully complete both phase I and phase II studies

In a phase III study, a drug is tested in several hundred to several thousand patients.

Provides thorough understanding of the drug's effectiveness, benefits, and the range of possible adverse reactions. Most phase III studies are randomized and blinded trials.

70 to 90 % of drugs that enter phase III studies successfully complete this phase of testing. Once a phase III study is successfully completed- approval for marketing the drug.

In late phase III/phase IV studies, pharmaceutical companies have several objectives:

(1) studies often compare a drug with other drugs already in the market;

(2) studies are often designed to monitor a drug's long-term effectiveness and impact on a patient's quality of life; and

(3) many studies are designed to determine the cost-effectiveness of a drug therapy relative to other traditional and new therapies.

Funding for clinical research comes from both the federal government (through the National Institutes of Health) and private industry (pharmaceutical and biotech companies).

The sponsor of the research hires physicians, who may work in a wide variety of health-care settings, to conduct the clinical trial.

Physicians are typically paid on a per-patient basis. The medical care is often provided free to the patient.

Global Pharmaceutical market- US $ 427 billion R&D costs-US $ 60-65 billion 70% of R&D money goes towards drug

development Clinical Trail Research-70% of

time&money spent-US $ 13 billion

Focus on reducing costs of clinical development

Contract Research Organizations gaining importance

Timely clinical trails extremely important,on account of steadily increasing number of global studies

Increasing global trend towards collaboration and outsourcing

Market today is estimated at US $9 billion

Age of globalization Share resources and benefits Global pharmaceutical industry

undergoing a paradigm shift New technologies in R&D,health care

costs,consumerism and uniform IP laws are making companies to rethink and re-align strategies

Focus on R&D productivity, reducing development time and controlling overall R&D expenditure

Indian pharmaceutical industry fast growing Health care market US $ 40-50 billion Global in outlook,focus on R&D and NNDS Tremendous potential for Clinical Research Potential opportunity US $ 2 billion by 2010 Between 1991-2001 performed clinical

research is estimated US $ 70-80 million

India is getting to be known as a hot destination for executing clinical trials.

In this mad melee, what are the determinants of success?

How real is the promise of clinical research in India and what will make or break a new entrant in this business?

for contract pharma research and development due to

its huge treatment naïve population, human resources- Annually 27000

doctors qualify in India technical skills,

adoption/amendment/implementation of rules/laws by regulatory authorities, and

Changing economic environment.

Present- 400-500 PI in India Year 2010 India needs 2000-3000 PI 500-1000 Centres of excellence in clinical

research 1,00,000 study coordinators, monitors,

project managers. Medical coleges- 254 –offer MBBS Large hospitals, corporate, private, govt Centres of international standards for

inspection, site selection.

2000-2005 - 3-5 billion $ 2010- 10 bilion $ 3% of global clinical research –India Next 5 years 15% of global clinical

research to be out sourced to India. Are we ready?

Cost effective? Quality of data? Speed of recruitment India-China 20% of world population Knowledge base to skill based Contract research to architects of

protocol- design & devt.

Language-English vs China, Japan Patient diversity- North , South- West-East 1.136 billion- 5% sickness/disease-

Inexhaustible patient pool Communication Hospitals, Qualified Doctors Nurses, beds,Graduates, universities,

Colleges 2 largest number of technically qualified

people in the world Urban vs rural

China- 1 major language- many dialects India- 24 major languages, 1600 dialects Many don’t have script Cost of translation Infra structure- Air connectivity- Electricity-Fax- Internet Training, acridition- PI, CI, study

coordinators, Monitors

Regulatory authorities Ethical committees Poor, illeterate patients Doctors consider CR as second rate

profession Prescription docs Laboratories- Standard Record keeping- Electronic data capture

Capacity building Infra structure improvement COE for clinical research Train CRA, PI, CI, Monitors-Research

academies Your role- CRA- project manager- VP- own

a CR centre of excellence.