T 39: Bangladesh: A New Frontier for Global Clinical Trials
This abstract details the development of new GCP standardized clinical investigator sites that have diverse disease profiles and large patient base in a country traditionally overlooked for global studies. This effort involved the creation of a SMO to assist and oversee Investigator efforts.
Over 80 sites from 23 countries are participating in the AURA study in lupus nephritis(LN), a rare disease requiring the use of a global approach to recruitment. Patients were required to have a local kidney biopsy, centralized ECG testing, along with PK sampling and blood work over 50 weeks.
Prior to study patient enrollment, sites were chosen based upon clinical expertise in this rare disease. Study teams were created and GCP training was conducted by the CRO among all staff involved in the study. A refresher course was conducted during study participation to ensure GCP standards were maintained.
The total time required in Bangladesh to obtain central as well as the site IRB approvals was 4 months. One month was required for Import permits by the Directorate General of Drug Administration (DGDA) and export of biological samples by the Ministry of Commerce. Although the initial country target was to enroll a maximum of 25 patients from Bangladesh, quality in clinical care and ensuring the ICH-GCP guidelines were closely and constantly maintained allowed for an increase in countrywide enrollment.
Among the 7 Asia-Pacific countries, the proportion to the patient screened to randomization indicates a higher patient yield in Bangladesh - 46/62 (74%); followed by Philippines 44/67 (66%) and Thailand 13/19 (68%). There were regular country-wide IRB (including members from local site IRBs) safety review meetings held to ensure patient safety and compliance with ICH-GCP guidelines. Any protocol deviations required explanations from investigators. A proper courier service was established ensuring sample shipment as per study schedule, and ensuring shipment clearances on time at customs resulting in no delay or halt of sample exports. Repeated renewal of IP import through DGDA were done without any interruption.
80% of clinical studies fail to meet enrollment deadlines, and 50% of sites enroll 1 or no patients. Effective therapies remain unavailable to almost all patients with rare diseases. Yet, studies requiring FDA submission need to reexamine global approaches. Consideration of Bangladesh as a part of a global study involved intensive efforts to clarify study conditions and investigator qualifications, along with study supports ensuring ICH-GCP compliance. Sponsor/CRO review included the use of icddr,b (International Center for Diarrheal Diseases Research, Bangladesh) globally known for their invention of ORS to play a key role in Investigator oversight.The icddr,b IRB has the FWA (Federal Wide Assurance number from USA) and is approved by a special act of the Government of Bangladesh to be an independent body to approve and to conduct clinical trials in Bangladesh. This IRB meets monthly and in occasion arranges special meeting for expedited CT reviews.
Bangladesh was the highest patient recruiter overall. The highest number of patients randomized following screening in Bangladesh (74%) not only ensures availability of such patients but also indicates the clinical experience of the investigators to pick appropriate cases early on as per the study inclusion criteria. That results in faster recruitment, saving unnecessary investigations and reducing overall study cost.
Bangladesh a country of over 160 million with many treatment naïve patients; increased number of lifestyle diseases are emerging with the change of the economy of the country from low to middle income country. Young physician Investigators have their medical training in English, and are trained in the same standard as UK Investigators. These combinations can be a potential game changer for international clinical trials and global CROs to explore in this newly emerged clinical research country.
Additional authors: Mohammad Mahbubul Karim, Mohammad Sharif Hossain, Rashieda Gluck, Robert Huizinga