Meeting the challenges at investigative sites: the situation in Asia: Meeting the challenges at investigative sites: the situation in Asia Nermeen Varawalla, MD, DPhil (Oxon), MBA Vice President, Corporate Development, PRA International Applied Clinical Trials European Summit Amsterdam, October 2006


Meeting challenges at investigative sites in Asia: Meeting challenges at investigative sites in Asia Leveraging the opportunities Recognising the potential hurdles Defining approaches to effectively work in Asia Looking ahead Agenda


Including emerging geographies for late stage clinical trials: the balancing act: Including emerging geographies for late stage clinical trials: the balancing act Nascent clinical development environments Prolonged regulatory processes Relatively poor commercialisation potential Ethical dilemmas Concerns regarding Intellectual Property protection Large patient populations with diseases of both developed and developing world Fewer competitor trials Keen investigators Potential for cost savings High growth markets of tomorrow Attractions Challenges


Access to large patient populations enables rapid recruitment. : Access to large patient populations enables rapid recruitment. 3 million diagnosed cases 0.7 million new cases are detected every year as compared to 1 million new cases detected in the US Cancers of the oral cavity, lung, and cervix form over 50% of cases Other common cancers are those of the breast, head & neck and pancreas The comparatively less intensive medical surveillance suggests the true cancer caseload would be significantly higher Standard of care not dissimilar to US and Western Europe - Example: Cancer in India - The speed of patient recruitment for oncology clinical trials in India is up to seven times faster than in the United States.


Asia has motivated physicians keen to participate in global clinical trials.: Asia has motivated physicians keen to participate in global clinical trials. India has over 500,000 medical doctors, 171 medical colleges and 17,000 medical graduates each year Medical education in India is delivered in English - based on the British system Majority of physicians are well trained, fluent in English and computer literate Most of India’s leading specialists have received post graduate medical training in the USA or UK A large and growing number of GCP (Good Clinical Practice) trained physicians keen to participate in international clinical trials Physicians are able and willing to meticulously adhere to study protocols Strong patient-physician relationships encourage high levels of patient retention - Example - Medical Workforce in India -


Healthcare delivery facilities in Asia are suited for global clinical research.: Healthcare delivery facilities in Asia are suited for global clinical research. Mixture of private and state subsidised healthcare The vast majority of specialist care is provided by state funded general hospitals at a fraction of developed world costs University teaching hospitals with state of the art facilities & technologies and hundreds of in-patient beds provide diagnostic, therapeutic and support services in all major therapeutic areas Private healthcare is of a world class standard Hospital centric healthcare model About 70% of hospitals are in urban areas Patients from rural and small town settings travel to urban specialist centres for treatment Community healthcare delivery differs from the Western model Recent investment has equipped Asia’s hospital to developed world standards but at relatively low costs The cost of health care provision in India one-third that of the Western world Health insurance coverage is low


Asia offers a wide choice of investigative sites. : Asia offers a wide choice of investigative sites. INDIA CHINA East ASIA Queen Mary University Hospital, Hongkong with 1400 beds serves a population of 1.5 million people Singapore’s National University Hospital - a 930 bedded acute and specialist hospital Veteran’s General Hospital, Taipei, Taiwan has 440 specialists, 300 beds, 2.5 M patients attend out patients clinics and 1 M receive in patient care per year The National Taiwan University Hospital has 4,000 staff serves approximately 0.6 M inpatients and 2.4M outpatients per year Renji Hospital, Pudong Shanghai has 1,000 beds & 2,300 staff Ruijin Hospital, Shanghai has 1,385 beds & 3,242 staff Peking Union Medical College Hospital is upgrading to better serve international sponsors


Sites in metropolitan India are becoming experienced and busy.: Sites in metropolitan India are becoming experienced and busy. Mumbai New Delhi Bangalore Ahmedabad Hyderabad Key Oncology Sites in Main Cities


Tata Memorial Hospital, Mumbai is ideal for oncology studies.: Tata Memorial Hospital, Mumbai is ideal for oncology studies. 25,000 cancer patients visit each year not only from India but also neighbouring countries 1000 patients attend out-patients clinics each day 441 in-patient beds 10,000 major operations each year 5,000 radiotherapy and chemotherapy treatments delivered each year Equipped with spiral CT scanner, gamma cameras, linear accelerator, bone marrow transplant facilities etc. The Clinical Research Secretariat co-ordinates clinical research activities that have been reviewed and approved by the Scientific Review Committee and Ethics Committee


Clinical sites are being developed away from the main metropolitan areas.: Clinical sites are being developed away from the main metropolitan areas. Pune Lucknow Jaipur Hyderabad Kochi Key Oncology Sites in India’s “2nd tier” cities


Slide11: Global clinical trial activity in India is exponentially increasing. No. of global oncology clinical trials conducted at Nizam Institute of Medical Sciences, Hyderabad, India (N = 45) Phase


The nascent clinical trial environment underlies the challenges in Asia. : The nascent clinical trial environment underlies the challenges in Asia. Regulatory approval process more streamlined & predictable Study start up 12 weeks from regulatory submission Regulatory approval timelines need to further decrease, particularly in China Government initiatives to strengthen ethics committee approval processes Recognition of critical importance of informed consent Overall benefit to healthcare delivery Data for pivotal studies accepted by the FDA / EMEA Successful FDA audit in India, Taiwan, Hongkong – no findings Investment in education & training: state & private Quality Regulatory Approvals Ethics India appears to be committed to uphold and enforce Intellectual Property protection as per international standards Although China too appears intent to protect IP sponsors remain sceptical IP Protection


Smart design of a global late stage clinical trial that includes Asia.: Smart design of a global late stage clinical trial that includes Asia. Divide patient enrolment between North America, Western Europe & Emerging Countries – “1/3rd each” Include 4-5 Emerging regions Include at least 10 centres / region to enrol at least 100 patients Utilise study start up time to identify investigators & subjects Confirm protocol feasibility Ensure resources are in place Initiate the trial in the US – FDA IND valuable Perform the vast majority of global data management in India Reduce patient recruitment times Address commercial imperatives Mitigate risk Capture efficiencies Goals Actions


Access to an experienced investigator pool who maybe utilised for numerous trials is valuable. : Access to an experienced investigator pool who maybe utilised for numerous trials is valuable. Recognise that the physician, investigator and KOL are almost always different individuals Experienced investigators are a valuable asset costs of identifying, assessing and training an investigator are rising contracting and operational processes are faster second time around better able to forecast patient enrolment better able to meet expectations aided by site support staff Pool of investigators needs to continually extended across geographies across experience levels Managing Investigator Networks


Building & Nurturing Investigator Networks in Asia. : Building & Nurturing Investigator Networks in Asia. Recognising critical importance Patient Access Data Quality Ethical Integrity Growing the Investigator Pool Pro-active acquisition Training Nurturing Investigator Networks On-going training / education Fair reimbursements Site level support – research fellows, study co-ordinators Investigator & Site Relationship Management


Sound feasibility and site assessment underpins satisfactory data quality.: Sound feasibility and site assessment underpins satisfactory data quality. Meticulous Process Questionnaire designed to assess prevalent patient profiles, treatment practices and ethical questions Verification against literature, previous experience and other investigators Supporting Tools Centralised fax service Designated website with differing access levels Nurture Goodwill Value of time and knowledge recognised Use a “ballpark” feasibility as a precursor when study intent is uncertain Relationship driven Contingency plans Back up sites & countries


Growth of the global clinical research sector benefits the Asian patient.: Growth of the global clinical research sector benefits the Asian patient. Treatment arm study participants access biomedical innovation All participants enjoy improved care Injection of resources into local healthcare system Standards of medical practice improve: communication, record keeping, evidence based medicine Not exploitation! – provided ICH GCP standards are followed: informed consent, expanded access


Concerns about the functioning of Ethics Committees are being addressed.: Concerns about the functioning of Ethics Committees are being addressed. Local Ethics Committee exist in > 200 clinical centres ICMR (Indian Council for Medical Research) to review & audit the functioning of ECs introduce a national accreditation system for ECs develop the Independent Forum for Ethics Review Committees, a training body Revised Schedule Y of Drugs and Cosmetics Act has prescribed roles and responsibilities of ECs composition as per ICH GCP guidelines formats for the EC approval letter India Example


Looking ahead: Looking ahead Compelling fundamentals will drive the growth of the clinical development sector in Asia – in particular India International players will continue to contribute to development of the sector Initiatives to address regulatory, ethics and IP protection issues will be invaluable for the further growth of the sector The sector will contribute to an overall improvement in healthcare delivery


Questions…..: Questions….. Dr Nermeen Varawalla, MD, DPhil (Oxon), MBA Vice President Corporate Development, PRA International Pacific House Imperial Way, Worton Grange Reading, Berkshire RG2 OTD tel: +44 118 918 1025 fax: +44 118 918 1001 email: varawallanermeen@praintl.com website: www.prainternational.com