Clinical Research India Primer

Up until 2005, India was probably best known in the world of pharmaceuticals as a generic powerhouse. Due to poor laws around intellectual property, most multi-national biopharmaceutical companies did not seriously consider India as a destination for clinical trials. Numerous other challenges and roadblocks existed as well. But as the Industry began to globalize rapidly throughout the 90’s and early part of this decade, regulators, entrepreneurs and businesses began to recognize the significant economic opportunity that they were facing, as well as the opportunity to gain new credibility in the world of medicine, science and the international business community. The response was a profound and rapid change in the regulatory landscape related to research and intellectual property that has created an inviting market which is realizing true and sustained growth.

So what is the regulatory environment today and where does it need to go?

The regulatory environment has improved dramatically in a short time period, with development of a standardized and predictable regulatory review and approval process. There are a growing number of FDA compliant IRBs. To some degree the process can be even better than other parts of the world in that conditional IRB approval can precede Ministry of Health approval. Regulatory approval timelines are also very reasonable and because sites are largely new to clinical research or don’t have established business practices related to clinical research, PI and site contracts can take as little as 3-5 weeks. A Regulatory Affairs CRO India can assist global biopharmaceutical companies with effectively planning and placing their clinical trials in India.

A look at 1572 filings – the form an investigator needs to submit in order to participate in a US IND study – shows that a rapidly growing number of investigators are from India, far outnumber growth rates seen in other Asia-pacific regions such as China, Japan and Australia. Sponsors are finding that the regulatory timelines, data quality, costs and abundance of patients make India one of the most attractive countries in the Eastern world to run their studies.

The attractive aspects of the market are translating to a growth spurt in the number of studies taking place in India. An analysis conducted by Excel Life Sciences has identified a minimum of nearly 900 clinical trials taking place in India today, a number that is growing by double digits annually. This figure doesn’t take into account non US IND studies, investigator initiated studies and other studies taking place.

The well known consulting firm AT Kearney ranked the attractiveness of markets across the world using the US market as the benchmark. India ranks second only to China on that scale and other than population size ranks very closely to or better than China in a number of categories, including perhaps most importantly to many companies, the regulatory environment and timelines.

Epidemiology

Like many diseases in India, given the size of the patient population and lack of standardized healthcare, disease prevalence is often much higher than other regions of the world and many of the patients are treatment naïve. These factors typically result in shortened enrollment timelines and naturally reduced costs.

If you look at the breakout, it reflects those therapeutic areas made up of conditions that are most prevalent in India. These conditions to some degree represent the evolving and improving socioeconomic status of India – essentially lifestyle diseases, e.g. Cardiovascular conditions, Diabetes and other endocrinology conditions, as well as many types of cancer. For example:

Oncology/Cancer

Today there are an estimated 2.5M people in India suffering from cancer and that number is expected to grow significantly in the months and years ahead driven by strong growth in tobacco related cancers, as well as those that are environmentally driven as India continues to develop rapidly from an economic and lifestyle perspective. An Oncology CRO India can assist sponsors with finding and screening these patients for their clinical trials.

Cardiovascular Diseases

The overall incidence of heart disease has doubled in India during the last 20 years and this trend is expected to continue. The World Health Organization (WHO) estimates that 60% of the world's cardiac patients will be Indian by 2010. Our statistics show that between the years 2003 and 2006, top sites in India saw over 100,000 patients. A Cardiology CRO India may be used by a global biopharmaceutical company to identify and enroll these patients in a clinical trial.

Endocrine and Metabolic Disorders

An estimated 108 million people in India suffer from endocrine and metabolic disorders. Diabetes is the most prevalent disease in this therapeutic area with approximately 35.5 million cases. Our clinical investigators have experience conducting global trials and have access to a large and diverse treatment naive patient pool. In fact, these investigators see 400 - 500 new cases per month and provide treatment for approximately 2,000 ongoing cases per month. An Endocrinology CRO India and Diabetes CRO India like Excel Life Sciences can assist global biopharmaceutical companies with identifying and enrolling the right patients for their clinical trials.

Neurology

India has a high prevalence for neurological and psychiatric diseases and disorders. Our statistics show that between the years 2003 to 2006 some of the leading sites in India saw over 30,000 psychiatry and over 40,000 neurology patients respectively. Although many people are already being treated, the majority are not. The World Health Organization (WHO) estimates that at minimum, an additional 25 million people in India are in need of mental health services. A Neurology CRO India or Neuropsychiatry CRO India like Excel Life Sciences can assist global biotech and pharmaceutical companies with identifying the right Neurology patients for their clinical trials.

Contract Research Organization India / CRO India Support:

There are several different models and configurations that exist today in terms of who sponsors might partner with to place and conduct studies in India. The least common way is through Sponsors identifying and hiring their own sites. You really don’t see much of this and sites haven’t built up the confidence and business know-how to be soliciting business with Sponsors on their own.

Instead there are 2-3 common models that exist. What makes Model #1 interesting from a US perspective is that it involves the use of a Trial or Site Management Organization – terms and concepts that have a slightly negative connotation in the US and Western Europe as a promise largely gone unfulfilled. In the US the SMO concept peaked during the 1990’s and early part of this decade, but many of the SMOs found that sites didn’t need or appreciate the support and that sponsors weren’t willing to award them more than a handful of sites in many cases. In India though, the concept is thriving. Largely due to the vast network of inexperienced sites, who:

1. Don’t have the know-how or means to market and contract their own business – so the SMO acts as the lead generator.

2. Need the support of a full-time CRC from the SMO for day-to-day study conduct, which due to large patient loads, the investigator does not have the time to manage.

So, this model is being used more often, where Sponsors looking to place a study in India work with an TMO/SMO to handle all aspects of regulatory, site selection, patient enrollment and so on and then the SMO contracts with a CRO to handle the monitoring aspect of the study, therefore avoiding a conflict of interest. This is why these companies are now being referred to as Trial Management Organizations, because they handle most of the activities that traditional SMOs and CROs handle without conducting the monitoring.

Sponsors are finding that day-to-day site management is critical in India since there are often first time investigators involved in a study and more importantly, the patient loads and activity level at each site, warrant the placement of and support from a full-time CRC. In general, sponsors are finding that patients are enrolled faster, retained better and that there is higher quality data coming from the site when a SMO is involved. In profiling more than 900 sites across India, Excel Life Sciences found that less than 15% of all sites have a full-time CRC on staff. When a CRC is present, they are typically spread across multiple studies.

The Trial Management Organization in India is a hub of activity for a clinical study. This multi-faceted approach requires superior upfront and ongoing training as well as vigilant project management and site support.

A comprehensive site support model involves placement of a full-time, highly qualified clinical research coordinator at each study site to assist the investigators and site staff with all day-today study conduct activities. Coordinators must be trained to provide professional assistance to the investigator ensuring compliance with FDA, local regulatory and ICH-GCP guidelines and efficient completion of mandated tasks. Supported by an experienced project management team, the study coordinator can have a significant impact on the quality, ethics and performance of the site. CRC study conduct support activities can include, but are not limited to the following:

Prestudy:

• Regulatory Submissions
• Select PI
• PI Training Programs
• Patient data base
• IRB submission
• Pre screening
• Source Document (SD) templates
• Referrals

Study conduct:

• Identify patients, SIV
• Assist ICD
• Ensure SD
• Transcribe CRF
• Send lab samples
• Scrutinize results
• Maintain Trial Master File
• Prepare for monitoring & audit
• Track enrollment
• Ensure 100% follow up
• Timely payment of patient expenses

Post study:

• Query resolution
• Study close out