With the stringent global regulatory mechanisms announced by the US FDA (Food and Drug Administration) , European Medicines Authority (EMA) and the Drugs Control General of India (DCGI), the conduct of clinical trials is poised for a sea change worldwide.
The European Medicines Agency (EMA) has published the final reflection paper concerning ethical and good clinical practice (GCP) aspects of clinical trials. The framework provided in the paper applies to medicines for humans and enforced from May 1, 2012.
The USFDA too has now raised the bar for clinical trials data. In India, the DCGI has now started audit the clinical trial organizations and the creation of the Clinical Trial Registry of India (CTRI).
The big Indian opportunity
With the increasing number of patients affected with chronic and critical conditions and growing a population, there is need for newer drugs. At the same time R&D productivity of top pharmaceutical companies has declined over recent years, as a result of increasingly stringent USFDA regulations concerning the approval of new drugs.
Owing to falling revenue in the life sciences sectors, decline in drug productivity and diminishing discoveries of path-breaking medicines, western companies are making efforts to reduce R&D expenditure and increase profitability. They are outsourcing more clinical trial activities to Clinical Research Organizations (CROs ) in countries like India and China. Hence outsourcing clinical trial activities to CROs, particularly in the developing nations, is rapidly gaining acceptance in the industry.
In this context India has a distinct advantage with its English speaking and qualified professionals along with a large pool of medical experts, say industry veterans.
In India, there are over 120 clinical trial organizations. The leading names are Ecron AcuNova, Clinigene, Clin tech, Lotus Labs, Omnicare, Quintiles, Pharm Olam, ICON, Vaatsalya, St. John’s Centre for Population Studies, Synchron Research Services Pvt Ltd, SIRO Clinpharm, D2L, SMO India, G7 Synergon Life Sciences, ANSA, Anvihta and Triesta Life Sciences.
Worldwide the latest paradigm shift in the clinical trial methodologies and business models is taking a turn towards translational medicine. Interdisciplinary integration is being attempted at all stages for expedited drug delivery. Notable translational medicine tools to integrate are at the level of clinical practice and research, newer designs like adaptive trials, 'quick win fast fail strategies' like phase 0 (micro-dosing) studies, biomarker development, personalized medicine & pharmacogenomics, said Dr. Mufti Suhail Sayeed, Vice President, R&D, Venus Medicine Research Centre.
The Union government’s stringent regulations on seeking informed consent and providing compensation to clinical trial victims would increase the number of volunteers and patients going for clinical trials in India. Now CROs are taking up insurance policies to cover the patient compensation in the wake of an adversity. Several insurance players have also chipped in to support the CROs with dedicated policies. These include National Insurance, Oriental Insurance and MetLife, to name a few, say experts in the clinical research sector.
The stringent compensation clause is an assurance for the patients to participate in human study and for a clinical research organization to carry out the trial said Dr Banu Priya, director and head, clinical research, G7 Synergon Life Sciences Consulting.
India is increasingly being recognized as a hub for global clinical trials as it has several unique advantages such as large and diverse patient pool with western disease profile , availability of medical, pharmacy and science graduates, excellent facilities, comparative cost advantage and changes in the patent laws. Moreover pharma companies are also seeing the advantages of outsourcing due to the increasing success stories of outsourced trials compared to the in-house trials.
Indian patient population in most cases are therapy naïve. Cost of enrolling and paying patients is among the lowest in the world. More over the time required to complete trials is 30-50 per cent lesser in India.
There are over 10,000 hospitals in India currently undertaking clinical studies. Many fresh medical graduates are also keen to enter the space going by the lucrative packages offered by the multinational pharma companies. There are no language barriers between clinical investigators and patients. Another advantage is the advancement in information technology which streamlines processes, say industry cognoscenti
Need for adequate compensation
Since compensation to the victims of clinical trials is a critical area that is being neglected by the pharma companies and the CROs , it is essential that the government should stipulate adequate compensation to relatives of subjects who die during a trial or get seriously injured , say industry veterans.
However according to Shoibal Mukherjee, Chief Medical Officer, Quintiles India, healthy clinical trial volunteers in India are paid quite well by global standards. Volunteers generally receive Rs 6,000 to Rs 12,000 for a single dose cross-over bioequivalence study for which they have to spend 4 to 8 days at the facility. This range overlaps with developed countries where volunteers receive only slightly higher payment despite a much higher cost of living.
“As a general rule across the world, patients do not receive payment for participating in a clinical trial. However, they receive reimbursement of costs which may include travel cost as well as medical costs directly related to the trial. Since Indian patients usually do not have health insurance, sponsors tend to reimburse more of the medical costs in India than is the practice elsewhere in the world. This is particularly true for trials in life-threatening diseases. Some commentators feel that in developing countries, patients should be paid for study participation even though this could be considered an inducement elsewhere around the world,” Mukherjee added
"Worldwide, compensation for injury is generally paid only in response to a claim alleging misconduct or negligence. In India regulations require payment of hefty compensation for any adverse medical event if the doctor treating the patient feels that the trial may have had something to do with the event. On balance Indians are compensated on par with other populations for study participation, but receive much higher payments for putative study-related injury", informed the Quintile India CMO.
The impending issues
Despite the growth driven factors like India's naïve patients population which facilitates cost-competitive patient recruitment, significantly reduced cost for clinical trials compared to the Western countries and so on, there are certain challenges that are being faced by the international pharmaceutical companies. These issues include socio-economic & cultural barrier, genetic diversity, special regulatory and ethical needs, informed Dr. Sayeed.
Refinement in clinical trial designs
Pharmaceutical companies will be able to refine their trial designs to reduce the number of studies they perform and the number of patients on whom new medicines are tested. They will start by administering a treatment to a single patient who has been screened to ensure that he or she meets the inclusion/exclusion criteria, which are likely to include specific genotypic and phenotypic characteristics as well as the relevant disease subtype, reports PriceWaterhouseCoopers (PwC) in Pharma 2020: Virtual R&D analysis.
The clinical trial industry has traditionally focused on establishing whether new molecules are safe and efficacious, not on whether they provide value for money. In future, it will address the payer’s perspective. By 2020, pharmaceutical companies will collaborate with healthcare players in different jurisdictions to develop criteria for assessing the value of new treatments which provide measurable increases in efficacy and ease of compliance, decrease healthcare costs and integrate these criteria into their trial protocols, the PwC report says.
Further, PwC has predicted that by 2020 the clinical environment would marry the needs of patients, players and providers and regulators by working much more closely on a common agenda agreed upon among them.
According to PwC, as the current system of conducting trials at multiple sites is inefficient. By 2020, it will be replaced by a system based on clinical super centres. There will be one or two per country, perhaps to recruit patients, manage trials and collate trial data. The super centres will be owned and run independently of the industry, possibly by a new generation of site management organizations. These will act as centres of excellence in the delivery of new medicines to patients.
“Two technological advances will be necessary to facilitate this transition. These will be through electronic data interchange and electronic medical records. The diversity and complexity of the information that is generated by the life sciences sector has long been a major barrier for ‘interoperability’. However, the US FDA and EMA are actively promoting the creation of common formats for collecting and reporting biological data. Various standards-setting organizations, including the Clinical Data Interchange Standards Consortium and Society for Clinical Data Management, are also working towards this end. They have already made considerable progress in simplifying the standards that are used to exchange clinical data between pharmaceutical companies, contract research organizations, trial investigators and the regulators, although many challenges remain. There is still, for example, no consensus on how different data and applications should be integrated, or a set of common business processes for performing many clinical activities. Nevertheless, these problems will be resolved within the next 12 years. Use of electronic medical records will also be widespread by that time. These initiatives would transform the way clinical trials are conducted globally,” the PwC report adds.