Clinical trial data is complex and has huge volumes. Inconsistency of data between multiple systems results in data conflicts and efforts, problems in compliance, validation requirements, polices and procedures. Clinical trials industry globally faces similar issues. Expert researchers from pharma and biotech sectors alongwith the experts in regulatory issues should come together to develop a national consensus and initiate policy decisions to develop standards, policies and procedures.
Clinical trials are the links between advances in drug discovery and improved healthcare. The ever lasting conquest for prevention of disease requires rich and authentic information about disease incidence in the population, probable causes and results of drug trials conducted.
Over the last couple of decades, there has been exponential growth in the number of clinical trials conducted worldwide. India has seen sizable growth of Clinical trials industry in last decade and holds the promise to continue the same in future. Any such dramatic growth always faces challenges. The challenges are many. Inspite of the weaknesses like lack of strict regulatory regime, governance, management of data and records, the industry in India has not only survived but proliferated aggressively.
Clinical research organizations (CRO) have been instrumental in strengthening India’s growth story. India is one of the preferred destinations for clinical trials. Growth in numbers of clinical trials conducted has led to increased competition among sponsor companies and CROs to find clinical sites and to recruit clinical investigators and treatment-naïve patient populations.
The need for clinical trials:
Medical research has progressed studying medial records over years. Review of studies and publications are very important in medical research. Data obtained on human subjects is of utmost importance for further research.
A clinical trial is a systematic study of pharmaceutical products in human subjects, in order to discover or verify the clinical, pharmacological and adverse effects for determining the safety and efficacy.
Clinical trials are defined as Pre-planned studies of the safety, efficacy, or optimum dosage schedule of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavourable effects.
Scientific research has developed well-established, well documented and validated methods for the design, conduct and analysis of clinical trials over years. The entire drug discovery process is very lengthy and complex spanning over 10 to 15 years making it very expensive. Clinical trials, being the tail-end and most important of the entire process, demand critical attention. The outcome of clinical trials has major impact on the manufacturer’s interests and efforts and also on prognosis of disease. Although drugs hold a hope for certain critical medical conditions, they require very careful analysis of desired outcomes and side effects in human subjects. The failure of desired outcome can make a drug company run into losses of millions of dollars. It is thus important to have a stringent control on clinical trials. The trials involve human subjects, making it a very sensitive issue. Accordingly legal implications involved in clinical research are complex.
Thus clinical trials are not only important to a drug company and patients but also to government, regulators, media, different advocacy groups, ethical police, media, and the general public.
There has been as a steady increase in the drugs in the development pipeline with advancement of genomics, bioinformatics, high throughput analysis etc, making the efficient use of resources very important. Drug companies, pharmaceuticals and medical-device manufacturers who would conduct trials on their own, have gradually realized the benefits of outsourcing clinical research. The concept of CRO is now well established and the budgets used for CRO contracts are on the rise all over the world.
Clinical research organizations:
Clinical trials are heavily regulated, which in part is a reason for drug companies to start outsourcing services, resulting in the growth of clinical trials industry. Over the years, CROs have proved as the trusted service providers for pharmaceuticals and bio-medical organizations. CROs offer a range of expertise, such that along with conducting actual clinical trials, even pre-clinical management is taken care of. However, their core competencies are still in managing human trials.
The unprecedented growth in Clinical research industry is estimated to be worth over USD 52 billion and has employed more than 2,00,000 people in USA alone.
The salaries too are very attractive and have attracted attention of many students, especially medicos. They perceive it as lucrative career with good employment opportunity.
India has become a strategic centre to conduct clinical trials. Today's CROs operate on an international scale, conducting trials in multiple countries concurrently under the supervision of multiple regulatory bodies.
This industry is evolving toward a full-service model. Smaller CROs with niche provisions are merging into or being acquired by organizations that are more focused on offering a complete range of services.
This has resulted in CROs providing services from early drug-safety trials (Phase I), through regulatory approval (Phase IV) with research efforts required alongside.
It is estimated that currently, more than 50 per cent of the clinical trials are handled by CROs, with value added services. The success of CROs to conduct more and more complicated trials is now proven. Since the requirement of this industry is very crucial, CROs have a steep performance curve. There is greater competition as well, resulting in substantial growth.
Many major pharmaceutical industry players are conducting trials in India with the help of either their in-country partners, or have on-the-ground presence. India has witnessed growth in pharmaceutical business also resulting in increase in outsourcing to India.
It is forecasted that, by 2012, India will be conducting 5- 15 per cent of total global clinical trials.
Advantage India:
India is emerging as a fast growing economy. As regards clinical trials, there are many factors that are in favour of India as a preferred destination. According to McKinsey and Co., by 2010 global pharma majors would be spending up to $1.5 billion for clinical trials in India.
The prime most factor is that medical knowledge available here is well respected. This has also given rise to medical tourism as another booming industry in India. India offers specialty hospitals with state of the art facilities even in smaller cities. India also offers very good educational support resulting into thousands of medical graduates. The Medical Council of India currently recognizes 273 Indian medical colleges, with a total capacity to train 31,298 Indian medical students.
There are also a large number of students graduating in different fields of life sciences and information technology every year creating a large brain pool of qualified and efficient professionals. The proficiency in English is an added advantage to make India a preferred clinical trial hub.
India has workforce that can easily be trained into the pattern that suits USA/Europe work practice. Many satisfied pharma clients are proof of meticulous and scientific professionalism of Indian CRO workforce. E.g., Quintiles has sailed through all five audits of its clinical work by the FDA. Many drugs have been approved in Europe and the U.S. with significant data from India.
Since an ideal study design should have sufficient sample size and statistical power and proper control of bias to allow a meaningful and statistically significant interpretation of the results, countries like India and China are growing rapidly in this sector. India has a large and ethnically diverse population, resulting in great variety of medical conditions. Patients are easier to recruit as compared to western countries. India has among the largest pool of patients suffering from different ailments such as, cancer, diabetes, hypertension, asthma, tropical infections and degenerative diseases.
India's patient population estimates
● 40 million asthmatic patients
● 34 million diabetic patients
● 8-10 million people HIV positive
● 8 million epileptic patients
● 3 million cancer patients
● 2 million cardiac related deaths
● 1.5 million patients with Alzheimer's disease
● 15% of population is hypertensive
● 1% of population suffer from schizophrenia
Another important advantage India has is that, drug trials can be carried out in India at extremely competitive costs. Both facilities and Staffing costs are economically attractive in India.
Initiatives like, increasingly compliant regulatory affairs and Intellectual property protection by strong government support will be a positive measure for CROs. Additional support in terms of infrastructure improvement will contribute further to growth of clinical research industry.
An indicator of India’s stronger presence in clinical research for the pharmaceutical sector is the recent opening of US FDA office in New Delhi.
Briefly, the advantages India enjoys are
● Huge patient base with diversity of diseases
● Heterogeneous population
● High enrollment
● High patient compliance / retention
● State-of-the-art hospital facilities
● Reliable, well-trained investigators
● English-speaking workforce
● High ICH GCP quality standards
● Cost effectivity
● Good IT infrastructure
● Increasingly compliant regulations
Clinical trial research: Challenges
Clinical research, is a highly regulated industry and hence there are many crucial components to running a CRO.
Apart from need for medical treatment, patients opt to participate in clinical research for many other reasons as well. Some may desire early access to new, still experimental medications or even try to reach to highly sought after physicians or specialists. Others could opt to obtain medical care not covered by their insurance plans. Even to reach out to other patients suffering the same ailment could be a reason too. Opportunity to remain under vigilance for their conditions is also motivating. Patients may also be paid for their participation in studies. This however may contribute to the hidden costs, as most of India’s population does not have health insurance. Those costs have to be covered by the sponsors.
What has been discussed earlier as an advantage however could be a challenge when the same patient registers for different trials. Multiple enrollments are a problem faced by the CROs. Such cases, even if less frequent, could be a problem as drug interactions may give altered results. Retaining patients for post-trial assessment is another challenge. Long term analysis is a major problem in many trials. Another issue that many face is when trials are not done at site but drugs are given and patients are supposed to do regular follow-ups. Both, certainty of proper dosage and regular follow-up, could get affected.
These trials are the scientific studies of medication use in people to assess the specificity, efficacy and safety of new drugs. It is because of these volunteers that improved drugs can be found. All these factors call for a strict regulatory compliance. However, it also raises many issues that pose as a hurdle, such as regulatory uncertainties about time for approval, involvement of multiple agencies for approval and for processing import/export licenses. Several other factors also delay the trial resulting in losses. Regulatory approvals in India can take three months or more, compared to 30 days in the US.
Data exclusivity is a prerequisite for the protection of research efforts. India is yet to comply fully with the TRIPs requirement of providing data exclusivity. A much tighter IPR environment is the need of the time in the highly confidential industry of clinical research.
Experts in industry opine that one concern about confidentiality protection is that the needs of clinical research are not often explicitly addressed.
Clinical research: Medical perspective
Registration of clinical trials is now taken seriously and The Clinical Trials Registry- India (CTRI) has been set up by the ICMR's National Institute of Medical Statistics (NIMS) and is funded by the Department of Science and Technology (DST) through the Indian Council of Medical Research (ICMR). It also receives financial and technical support through the WHO, WHO-SEARO, and the WHO India Country office
This will safeguard patient interests and ensure greater transparency, accountability and accessibility of clinical trials.
Another fallout of lack of regulations is that, majority of investigators lack knowledge of regulations, ethics and GCP (good clinical practices) and skills for clinical trial management. Sudden rise is clinical research has led to mushrooming of clinical trials education institutes, many of which are offering substandard education, concepts and knowledge. Large number of graduates being churned out by these institutes lack a formal course in management of clinical research. The first generation of researchers in clinical trials industry have acquired their knowledge either through mentor or by first hand experience, however, there is shortage of trained manpower. There is inadequate industry-academia collaboration for students to obtain proper training. If the projections made for the industry in 2010 are considered, there would be heavy shortage of trained investigators.
It is a trend in clinical trials industry to adopt a complete electronic information environment, gathering and reporting data through secure online channels. This has advantage of reducing errors and enhanced speed. The prerequisite will be high quality specific training. Lack of industry standards leading to inability to leverage global standards, such as Clinical Data Interchange Standards Consortium (CDISC) is often noticed.
Inconsistency of data between multiple systems results in data conflicts and errors, problems in compliance, validation requirements, policies and procedures. Clinical trial data is complex and has huge volume, which makes it increasingly difficult to analyze and process if it’s coming from multiple sources.
Clinical trials industry globally faces similar issues. The entire industry has a heterogeneous landscape owing to its sensitive nature. There are number of dimensions which differ from country to country resulting in most countries having their own sovereign view to these aspects.
Hence there is great variation in clinical trial approval procedures, in terms of documents required, time frame of getting them done etc. The countries need to come together to have consensus in reaching harmonious procedure. A tough task, as it is, would require contributions from experts with minimal interference from Pharma industry. Since the daily expenditure on clinical trials is huge, the companies are very sensitive too about the issue
Conclusion:
India has made considerable progress in clinical research during last few decades. It has the potential to be a key player in this highly remunerative and fast growing industry. With the global pharmaceutical company’s preference for outsourcing to reduce costs and retain competitiveness, India is considered as a preferred destination for contract research in the pharma sector.
Medically there is a great opportunity of conducting multiple studies in disease segments for new biomarkers and novel drugs – both yielding high value intellectual property.
India with its strength, can easily grab this opportunity, provided faster solutions are obtained by reaching consensus on the challenges faced by the industry. Academia-industry collaboration, stringent regulations and their strict compliance, friendly for intellectual property protection provisions are some of the steps needed to tackle challenges faced by medical community in conducting clinical trials. The issues outlined here are genuinely difficult and no easy and quick answers are possible. In fact many of the challenges outlined here, are in various stages of formulation and implementation both in India and worldwide since concern about these issues is widespread. Professional institutions like ICMR are addressing these issues in India. There is a need for better and proactive interaction among policy makers, health-care professionals and researchers. This is a complex but workable process. A clear understanding and a dialogue at all levels such as, scientists, clinical professionals, population scientists, ethical committees, advocacy groups, the FDA, the NIH and all local country specific governing bodies is needed.
- (The author has a doctorate in bio-technology. As a domain expert on Intellectual Property Rights, she is associated with Interlink as an expert since last three years) Courtesy Interlink Insight