Dr. Bhaswat S. Chakraborty

Pharmaceutical Industry & Clinical Research: Basic

Intro

Global Pharmaceutical Market• The global pharmaceutical market research

has been done by many companies– All indicate a significant growth of pharma

market in 2010-2011.

– The forecasting indicates pharmaceutical market growth of about 4 - 6% in 2010-2011.

– >$850 Billion

– Expected to grow at a 4 - 7% compound annual growth rate (CAGR) through 2013.

– >$975 billion by 2013

Global Top 20 Pharmaceutical Companies

Rank CompanyRevenue in $ Million(2010)

01 Johnson & Johnson 61,897

02 Pfizer 50,009

03 Abbott 30,764

04 Merck & Co. 27,428

05 Eli Lilly & Co. 21,836

06 Bristol-Myers Squibb 21,634

07 Amgen 14,642

08 Gilead Sciences 7,011

09 Mylan 5,093

10 Genzyme 4,516

Indian Pharmaceutical Market3rd largest (after US and European) generic market

in volume, 14th in valueIndia currently holds only ~2% share, but it has been

growing at approximately 10% per year

India is a leader in generic drugs and active pharmaceutical ingredients (API)

Now seeking to become a major player in outsourced clinical research as well as contract manufacturing and research

There are ~100 U.S. FDA-approved manufacturing facilities in India, more than in any other country outside the U.S

In 2010, almost 30% of all Abbreviated New Drug Applications (ANDA) to the FDA have been filed by Indian companies

India’s share of the global generics market is ~33% now

Top 10 Pharmaceuticals in India, as of 2010

Rank CompanyRevenue 2010 (Rs crore)

Revenue 2010 (Rs billion)

1 Cipla 4,198.96 41.989

2Ranbaxy (Taken over by Daiichi Sankyo in 2008)

4,162.25 41.622

3Dr. Reddy's Laboratories

3,763.72 37.637

4 Sun Pharmaceutical 2,463.59 24.6355 Lupin Ltd 2,215.52 22.156 Aurobindo Pharma 2,081.19 20.801

7GlaxoSmithKline Pharmaceuticals Ltd

1,773.41 17.734

8 Cadila Healthcare 1,613 16.13

9Aventis Pharma Limited

983.80 9.838

10 Ipca Laboratories 980.44 9.8044

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Dynamic Continuum of Drug Discovery

Clinical Research• Clinical research is a branch of medical science that

determines the safety and effectiveness of – Medications– Medical devices (including surgicals)– Diagnostic products and treatment regimens intended for

human use.

• These may be used for prevention, treatment, diagnosis or for relieving symptoms of a disease

• Ethical research, overseen and regulated by local and other pertinent Government authorities

• Regulators and Ethics committees review the research prior to conduct as well as after completion of a study

• Clinical research is often understood by four phases of Clinical Trials (Phase I – IV)

Global Clinical Research Environment Today• Large, multinational clinical trials preferred over

smaller, local trials– Pharmaceutical and biotechnology companies to

accelerate development timelines – Under tighter budgets and resource constraints

• Multinational trials aim to increase access to treatment of naïve subjects by enlisting sites outside of major markets, and to drive cost savings

• After a steep learning curve in the 1990’s, most large pharmaceutical companies and CROs now have systems for large, multinational studies: – Hardware and IT infrastructure harmony– Support in multiple languages– Responding to regulators’ queries from several countries

arriving at the same time• Successful management of large, multinational

clinical studies are more common now than before• Certain aspects, however, still require constant

oversight to avoid serious mistakes.

Largest Registry of Clinical Trials

• ClinicalTrials.gov (www.clinicaltrials.gov) is a registry and results database of federally and privately supported clinical trials conducted in the United States and around the world.– currently contains 113,598 trials – sponsored by the National Institutes of Health, other

federal agencies, and private industry– Studies listed in the database are conducted in 176

countries – 24 categories of diseases– gives you information about a trial's purpose, who may

participate, locations, and contact phone numbers– receives over 50 million page views per month 65,000

visitors daily

Map of All Studies in ClinicalTrials.gov

What is a Clinical Trial (CT)?• Biomedical or health-related

research in human beings following a pre-defined protocol

• Clinical Trials mean both interventional and observational types of studies– Interventional studies have the

research subjects assigned by the investigator to a treatment or other intervention, and their outcomes are measured

– Observational studies are those in which individuals are observed and their outcomes are measured by the investigators

Different Types of CTsTreatment trials test experimental treatments, new combinations

of drugs, or new approaches to surgery or radiation therapyPrevention trials look for better ways to prevent disease in

people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vaccines, vitamins, minerals, or lifestyle changes

Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition

Screening trials test the best way to detect certain diseases or health conditions

Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.

Different Phases of CTClinical trials are conducted in phases. The trials at each

phase have a different purpose and help scientists answer different questions:In Phase I trials, researchers test an experimental drug or

treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase II trials, the experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase III trials, the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.

In Phase IV trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

Participation in Clinical TrialsParticipants in clinical trials can play a more active role in

their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research

All clinical trials have guidelines about who can participate Inclusion/exclusion criteria The factors that allow someone to participate in a clinical trial are called

"inclusion criteria" Those disallow someone from participating are called "exclusion criteria“These criteria are based on such factors as age, gender, the type and

stage of a disease, previous treatment history, and other medical conditions

A participant must qualify for the study by I/ESome studies need patients with illnesses, while others need healthy

participants I/E not used to reject people personally

Benefits & Risks of Participating in CT

Benefits Clinical trials that are well-designed and

well-executed are the best approach for eligible participants to play an active role in their own health care

Gain access to new research treatments before they are widely available

Obtain expert medical care at leading health care facilities during the trial

Help others by contributing to medical research.

Risks There are risks to clinical trials. There may

be unpleasant, serious or even life-threatening side effects to experimental treatment

The experimental treatment may not be effective for the participant

The protocol may require more of their time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements

What Happens During a CT?

• Depends on the kind of trial being conducted– The clinical trial team includes doctors and nurses as well as

social workers and other health care professionals– They check the health of the participant at the beginning of

the trial, give specific instructions for participating in the trial– They also monitor the participant carefully during the trial,

and stay in touch after the trial is completed– Some CTs involve more tests and doctor visits than the

participant would normally have for an illness or condition– For all types of CTs, the participant works with a research

team– A CT is most successful when the protocol is carefully

followed and there is frequent contact with the research staff

Opportunities for India

United States

Western Europe

Rest of world

1997 86% 9% 5%

1999 80% 9% 12%

2001 77% 10% 13%

2003 70% 11% 19%

2005 62% 13% 25%

2007 57% 14% 29%

The Rise of Trial Outsourcing

•Source: Tufts Center for the Study of Drug Development analysis of FDA data

Outsourcing of CTs• Outsourcing can be defined as “the strategic use of outside

resources to perform activities traditionally handled by internal staff and resources”

• The basic rationale behind outsourcing:– In some cases, other companies can perform a service more

effectively and at a lower cost.• In pharma, the outsourcing of R&D activities offer the greatest

advantages• Pharmaceutical companies face extreme rising costs to

develop new medicines, capacity constraints and longer R&D timelines

• CROs offer services that can help to alleviate these constraints and increase efficiency and R&D effectiveness

• In the past decade, the global spending on new drug development has been growing at an annual rate of 9.1%

• However, the spending on contract clinical services has been growing nearly 50% faster – at an annual rate of 13.4%

Drivers of Outsourcing/offshoring of CTs• Developing countries have a high patient

enrolment rate compared to North America and Europe.

• High enrolment rates imply that clinical trials can be finished sooner, meaning that the profits of patent exclusivity can be enjoyed for longer.

• Other factors that determine the attractiveness of a country for the conduct of clinical trials include – a broad spectrum of diseases– a more rapid approval of trials– availability of human resources – technical skills– differing ethnic responses to drugs and cost

advantages– availability of a “treatment naïve population”

Van Huijstee M & Schipper I. 2011. Putting Contract Research Organisations on the Radar. Centre for Research on Multinational Corporations

Opportunities for CROs In the pharmaceutical sector, outsourcing of CTs offers the greatest

advantages becauseCT phase is the most labour intensive, time consuming and costly part of

the drug development process. Nearly 70% of the total R&D costs are spent on clinical trials

CTs are a key factor in the rising R&D costs because today’s drug trials are larger and more complicated on average and require more participants than ever before.

Recruiting participants is becoming more difficult in western countries.

In 2008, US pharma companies spent $32.2 billion on trials. Pharmaceutical companies are under pressure to bring more new

drugs to the market while at the same time they have to cut their R&D budgets. As a result, companies are increasingly outsourcing their R&D to CROsCROs offer services that can increase R&D effectiveness and at lower

costs. Currently, about half of the clinical trial activities are outsourced to CROs.

The CRO market is estimated to account for $24 billion in 2010. Van Huijstee M & Schipper I. 2011. Putting Contract Research Organisations on the Radar. Centre for Research on Multinational Corporations

The CRO Market

Source: Business Insights, The CRO Market Outlook, Emerging markets, leading players and future trends, 2008

Growth of CRO Market in India

Multi-centric CTs in India• Up to 7% of global Phase III and 3.2 percent of Phase II

trials.• The growth rate of the Indian clinical sector has been

estimated as two and a half times that of the global market.• Today, most of the big pharmaceutical companies are

conducting multi-centric trials in India with some of them are here >15 years. – Eli Lilly and Pfizer began their CTs here in 1995. – This was followed by Sanofi-Aventis, Bayer, Novartis Astra Zeneca

and Johnson & Johnson in the last decade. – Last 2-3 years have seen other big pharmaceutical companies, like,

Merck GlaxoSmithKline, Bristol-Myers Squibb and some of the larger biotechnology companies, like Amgen and Biogen Idec.

• However, all leading global CROs have also set up services in India (as seen before).

• India has about 30 established major CROs

Prioritization of CTs• Prioritization can be had based on national interest and

patient safety. – Clinical trials have different types of risks associated with

them. – A placebo trial involving vulnerable population (including

socioeconomically vulnerable) will have a higher risk and may be given a different priority.

– Higher risk trials need to have special monitoring and more intense review – a “site’s” ability to safely conduct the trials and the pool from which trial subjects are sought.

– A number of operational issues to implement such a system of priorities need to be discussed and procedures developed.

– A working group to measure risk associated with “site capabilities” needs to be constituted.

– This may be particularly relevant for approval of Phase 1 trials.

– Criteria for disallowing trials as well as guidelines for exceptions should be specified.

• Thank You•