Introduction to pharmaceutical industry & clinical research
Pharmaceutical Industr y &Clinical Research: Basic Intro Dr. Bhaswat S. Chakraborty
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 Revenue in $Rank Company Million(2010)01 Johnson & Johnson 61,89702 Pfizer 50,00903 Abbott 30,76404 Merck & Co. 27,42805 Eli Lilly & Co. 21,83606 Bristol-Myers Squibb 21,63407 Amgen 14,64208 Gilead Sciences 7,01109 Mylan 5,09310 Genzyme 4,516
Indian Pharmaceutical Market 3rd largest (after US and European) generic market in volume, 14 th in value India currently holds only ~2% share, but it has been growing at approximately 10% per year India is a leader in generic drugs and active pharmaceutical ingredients (API) Now seeking to become a major player in outsourced clinical research as well as contract manufacturing and research There are ~100 U.S. FDA-approved manufacturing facilities in India, more than in any other country outside the U.S In 2010, almost 30% of all Abbreviated New Drug Applications (ANDA) to the FDA have been filed by Indian companies India’s share of the global generics market is ~33% now
Top 10 Pharmaceuticals in India, as of 2010 Revenue 2010 Revenue 2010Rank Company (Rs crore) (Rs billion) 1 Cipla 4,198.96 41.989 Ranbaxy (Taken over by 2 4,162.25 41.622 Daiichi Sankyo in 2008) 3 Dr. Reddys Laboratories 3,763.72 37.637 4 Sun Pharmaceutical 2,463.59 24.635 5 Lupin Ltd 2,215.52 22.15 6 Aurobindo Pharma 2,081.19 20.801 GlaxoSmithKline 7 1,773.41 17.734 Pharmaceuticals Ltd 8 Cadila Healthcare 1,613 16.13 9 Aventis Pharma Limited 983.80 9.838 10 Ipca Laboratories 980.44 9.8044
Growth in Indian Domestic MarketRevenue in US$ Billion
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 ResearchEnvironment 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 ClinicalTrials• 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 trials purpose, who may participate, locations, and contact phone numbers – receives over 50 million page views per month 65,000 visitors daily
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 CTs Treatment trials test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy Prevention 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 CT Clinical 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 drugs risks, benefits, and optimal use.
Participation in Clinical Trials Participants 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/E Some 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
The Rise of Trial Outsourcing Western United States 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% •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 because CT 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 CROs CROs 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
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.