PRESENTATION ON CLINICAL TRIALS REGISTRY -AN INSIGHT BY: Snigdha Debnath Bioinformatics Institute of India
INDEX CLINICAL TRIALS REGISTRY–THE CONCEPT IMPORTANCE OF TRIAL REGISTRATION AND REPORTING INTRODUCTION TO CTRI CTRI DATASET WHO CLINICAL TRIALS REGISTRY PLATFORM ABOUT BII BII’s PROGRAMS IN CLINICAL TRIALS
Today, world over, a need has been felt on the imperative for transparency, accountability and accessibility in order to re-establish public trust in clinical trial data by registering the conduction of clinical trials in a centralized clinical trials registry.
In India, CTRI or Clinical Trials Registry-India, an organisation set up by National Institute of Medical Statistics, awards territorial rights for conduction of clinical trials in the country, in accordance with the governing principles of WHO's ICTRP (International Clinical Trials Registry Platform) and other ethics committees.
CLINICAL TRIALS REGISTRY–THE CONCEPT
Clinical trials are conducted to allow safety and efficacy data to be collected for new drugs or devices by testing them on human participants/volunteers.
The data and reports of various trials are often difficult to find and in some cases do not even exist as many trials are abandoned or are not published due to "negative" or equivocal results.
IMPORTANCE OF TRIAL REGISTRATION AND REPORTING Access to information about ongoing, completed and published clinical research is needed by researchers, research funders, policy-makers, medical practitioners, patients and the general public to help guide research or make treatment decisions.
Recently, a confluence of events has helped to form a general consensus – in the research industry, academia, and public policy communities – in support of a comprehensive approach for public registration and reporting of clinical trials. In particular:
An action brought by New York State Attorney General where complete disclosure of relevant clinical trial results might have affected prescribing behaviour.
Several pharmaceutical companies – including GlaxoSmithKline, Lilly and Merck – have announced plans or have actually begun their own trial registers. This announcement was further supported by an announcement by the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA).
Numerous medical research and professional organisations – including the American Medical Association – have urged comprehensive registration.
The International Committee of Medical Journal Editors (ICMJE) and British Medical Journal have called for public registration of clinical trials; the ICMJE stated that, beginning July 1 2005, only registered trials will be eligible for journal publication.
Clinical Trials Registry-India, as the name suggests, is a registry for clinical trials in India, set up by the ICMR's National Institute of Medical Statistics (NIMS) and receives financial and technical support through the WHO, WHO-SEARO, and the WHO India Country office.
INTRODUCTION TO CTRI
Anybody who wishes to conduct a clinical trial in the country would have to declare not only the twenty items of the Trial Registration Data Set as required by the WHO's ICTRP (shall be discussed later under CTRI Dataset and Description), but also a few more items relevant to the Indian scenario such as Ethics committee Approval Status, Regulatory Clearance by the DCGI (Drug Controller General of India), etc., before the enrolment of the first patient.
Setting up Clinical Trials Registry-India ensures that all clinical trials conducted in India are publicly declared and identifiable and a minimum set of information of all clinical trials is freely available to physicians, health researchers, academicians, pharmaceutical industries as well as the common man.
INTRODUCTION TO CTRI MISSION
The mission of the Clinical Trials Registry-India (CTRI) is to encourage all clinical trials conducted in India to be prospectively registered before the enrolment of the first participant and to disclose details of the 20 mandatory items of the WHO International Clinical Trials Registry Platform (ICTRP) dataset.
While registration is voluntary, only trials that disclose details of the 20 mandatory items of the WHO/ ICMJE dataset along with a few additional items, such as clearance from ethics committees and regulatory agencies will receive a full registration number and can be registered in the CTRI .
The vision of the CTRI is to ensure that every clinical trial conducted in the region is prospectively registered with full disclosure of the 20-item WHO ICTRP dataset, as well all items of the CTRI dataset. While this register is meant primarily for trials conducted in India, the CTRI will also accept registration of trials conducted in other countries in the region. Trials registered in CTRI will be monitored to ensure increasing voluntary disclosure of all items in the register.
VISION INTRODUCTION TO CTRI
These items have been selected in order to:
Improve transparency and accountability
Improve the internal validity of trials
Conform to accepted ethical standards
Lead to reporting of all relevant results of all clinical trials in India and the region.
CTRI Dataset and Description is a detailed account of various conditions that need to be fulfilled in order to secure registry for conducting clinical trials in India. Given below, is the complete CTRI Dataset.
Fields marked * are mandatory for registration to proceed.
The 20 items marked WHO need to be filled for gaining UTRN or Universal Trial Reference Number
Fields marked WHO* refer to the conditions whose fulfillment is pre-requisite under both CTRI and ICTRP norms.
Health Condition/Problem studied WHO Contact Person (Scientific Query) WHO Target sample size WHO Principal Investigator’s Name and Address Estimated duration of trial Secondary IDs, if any Date of first enrollment WHO Scientific Title of Study (Give Trial Acronym, if any) WHO * Regulatory Clearance obtained from DCGI * Public title of study WHO * Name of Ethics Committee and approval status * Trial Registration Date WHO Secondary Sponsor WHO Registration Number WHO Primary Sponsor WHO UTRN WHO *
CTRI DATASET Intervention and Comparator agent WHO Contact Person (Public Query) WHO Key inclusion/Exclusion Criteria WHO Funding Source/s WHO Method of allocation concealment Status of Trial * Blinding and masking Method of generating randomization sequence Site/s of study Brief Summary Countries of Recruitment WHO Study Type WHO Secondary Outcome/s WHO Phase of Trial * Primary Outcome/s WHO
WHO CLINICAL TRIALS REGISTRY PLATFORM ICTRP puts credence in the principle that “the registration of all interventional trials is a scientific, ethical and moral responsibility”. The mission of the WHO Registry Platform is to ensure that a complete view of research is accessible to all those involved in health care decision making. This will improve research, transparency and will ultimately strengthen the validity and value of the scientific evidence base. Structure of Organisation The WHO Registry Platform is a project within the World Health Organisation, involving the Research Policy & Cooperation Department (RPC) in the Information, Evidence and Research cluster (IER). The Secretariat has the following support structure:
International Advisory Board (IAB)
Scientific Advisory Group (SAG)
Register’s Working Group
Results Reporting Working Group
The International Search Portal WHO CLINICAL TRIALS REGISTRY PLATFORM The Search Portal is a web site that enables users to search a central database that contains the trial registration data sets provided by Primary Registers of ICTRP such as CTRI. When a user finds a trial on the Search Portal that they are interested in, they can learn more about the trial by clicking on a link that will take them to the relevant record in the source register. The Search Portal is not a clinical trials register. Two kinds of searches can be undertaken at the International Search Portal, viz. Simple Search Advanced Search
WHO CLINICAL TRIALS REGISTRY PLATFORM Registry Network ICTRP accepts data into the Search Portal from registries that meet specific criteria. Within the framework of the ICTRP, these registries are referred to as Primary Registries. In addition to primary registries, the registry network has provision for Secondary or Partner Registries as well which work in close relation with any single primary registry. PRIMARY REGISTRIES NEW ZEALAND AUSTRALIA INDIA SRI LANKA ISRCTN CHINA NETHERLANDS PARTNER REGISTRIES CLINICAL TRIALS.GOV, USA EUROPEAN UNION
WHO CLINICAL TRIALS REGISTRY PLATFORM Primary Registries
Functions of Primary Registries
Accept prospective registration of interventional clinical trials submitted by Responsible Registrants.
Participate in the development of Guidelines for Clinical Trial Registers. All registers will have documented Standard Operating Procedures (SOP).
Sri Lanka Clinical Trials Registry (SLCTR) The Netherlands National Trial Register (NTR) ISRCTN.org Clinical Trials Registry - India (CTRI) Chinese Clinical Trial Register (ChiCTR) Australian New Zealand Clinical Trials Registry (ANZCTR)
WHO CLINICAL TRIALS REGISTRY PLATFORM
Functions of Primary Registries
Be able to collect and display the WHO Trial Registration Data Set
Flag trials that do not provide the complete WHO Trial Registration Data Set at the time of initial registration.
Submit the WHO Trial Registration Data Set, in English, to the Central Repository.
Endeavour to keep registered information up-to-date.
Endeavour to maintain a publicly accessible audit trail so changes made to the WHO Trial Registration Data Set can be tracked.
Never remove a trial once it has been registered.
Be searchable over the Internet at no charge.
Publicly disclose ownership, governance structure and not/for-profit status.
Be managed by a not-for-profit agency
Be open to all prospective registrants
Note: Should a register cease to function the register agrees that at least the WHO Trial Registration Data Set (original and updated) for all trial records will be transferred to a Primary Register or appropriate alternative.
WHO CLINICAL TRIALS REGISTRY PLATFORM Comparative Study on Primary Registries Australian New Zealand Clinical Trials Registry (ANZCTR) The ANZCTR is advised by an external Advisory Policy Committee whose role is to advise on the scope, operation, accessibility, sustainability and international obligations of the ANZCTR. It is funded by National Health and Medical Research Council of Australia; New Zealand Health Research Council and managed by NHMRC Clinical Trials Centre, University of Sydney. The register URL is http://www.anzctr.org.au . The register is managed by National Institute of Medical Statistics (NIMS) and funded by India Department of Science and Technology (DST); Indian Council of Medical Research (ICMR); World Health Organization (WHO). The register URL is http://www.ctri.in . Clinical Trials Registry - India (CTRI)
WHO CLINICAL TRIALS REGISTRY PLATFORM The ChiCTR Advisory and Management Board consists of experts from the Chinese Evidence-Based Medicine Centre and Chinese Cochrane Centre, Ministry of Health of China, and United Kingdom Cochrane Centre. ChiCTR is funded by West China Hospital, Sichuan University. The register URL is http://www.chictr.org . ISRCTN.org Chinese Clinical Trial Register (ChiCTR) ISRCTN is a not-for-profit organization, funded through a fee per trial paid by trial detail providers. The register is owned by ISRCTN with Directors, Members and Member Organisations such as Current Controlled Trials Ltd, which administers the scheme on behalf of ISRCTN. The register URL is http://www.isrctn.org .
WHO CLINICAL TRIALS REGISTRY PLATFORM The Netherlands National Trial Register (NTR) The Dutch Cochrane Centre (DCC) is the managing agency behind NTR. The organisation is funded by ZonMw Netherlands Organization for Health Research and Development (main funding agency). Additional funding is obtained from the Health Council (Gezondheidsraad); Dutch Cancer Society (KWF) and Dutch College of General Practitioners (NHG). The registry URL is http:// www.trialregister.nl . Sri Lanka Clinical Trials Registry (SLCTR) The Sri Lanka Clinical Trials Registry Committee is nominated by the Sri Lanka Medical Association which is also the chief funding agency. The registry URL is http:// www.slctr.lk
WHO CLINICAL TRIALS REGISTRY PLATFORM Comparison Chart on Registry Criteria of Primary Registries Yes Under development Yes, under development Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry have documented Standard Operating Procedures (SOPs)? Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry accept prospective registration of interventional clinical trials submitted by Responsible registrants? Registry Criteria
WHO CLINICAL TRIALS REGISTRY PLATFORM Initial training of staff in the submission and query processes; conduction of regular audits; timely reviewing of SOPs Under development Under development Well trained staff; regular statistical and qualitative analysis of trial records; regular reviewing of SOPs. Information currently unavailable Information currently unavailable ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Description of the compliance mechanisms: Yes Under development Yes, under development Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Are mechanisms in place to ensure compliance with these SOPs? (e.g. staff training) Registry Criteria
WHO CLINICAL TRIALS REGISTRY PLATFORM Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Is the Registry open to all prospective registrants? Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry agree to participate in the development of Guidelines for Clinical Trial Registries? Registry Criteria
WHO CLINICAL TRIALS REGISTRY PLATFORM Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Can the Registry collect and publicly display the WHO Trial Registration Data Set (TRDS)? English English, Chinese English English English English ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Languages in which the registered information is displayed: Registry Criteria
WHO CLINICAL TRIALS REGISTRY PLATFORM On submission of trial for registration, its assessment by ANZCTR staff for completeness, identification of queries, if any and suggestion of changes to resolve them. Trial registered only on satisfactory completion of all data. Two step process-Initial control performed by assessor for verification of proper filling of 20-item dataset, followed by final control by final checking. Initially done by two scientists manually. To be done electronically at later stage. Mandatory provision of all 20 items at application stage, verifies that content is provided for all fields and that the content is applicable. If all the information is not provided, the trialist is contacted and the reasons why are recorded. Application of login code a must before registration of trial; checking and re-checking of contact and other details given in registration form; regular updating of information non-acceptance of incomplete submissions, except when only a few items are missed; deletion of trial lacking crucial information from register. Cross-checking of applications by Administrator before acceptance; requesting applicants to re-submit incomplete applications; holding monthly meetings regarding completeness and accuracy of applications. ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Quality control measures to make sure that all 20 items in the WHO TRDS are as complete and accurate as possible: Registry Criteria
WHO CLINICAL TRIALS REGISTRY PLATFORM N/A; Trials with incomplete WHO TRDs are not accepted for registration Yes Yes No Information currently unavailable Information currently unavailable ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry flag trials that do not provide the complete WHO Trial Registration Data Set at the time of initial registration? Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry agree to submit the WHO Trial Registration Data Set, in English, to the Central Repository? Registry Criteria
WHO CLINICAL TRIALS REGISTRY PLATFORM Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry agree to maintain a publicly accessible audit trail so changes made to the WHO Trial Registration Data Set can be tracked? Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry agree to keep registered information up-to-date? Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry agree to never to remove a trial once it has been registered? Registry Criteria
WHO CLINICAL TRIALS REGISTRY PLATFORM Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry publicly disclose ownership, governance structure and not/for-profit status? http://www.anzctr.org.au . http://www.chictr.org http://www.ctri.in http://www.controlled-trials.com/isrctn http://www.trialregister.nl http:// www.slctr.lk/faq.asp ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR The web address where this information is displayed: Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Does the Registry agree to inform the WHO ICTRP Secretariat of changes that may be relevant to its status as a Collaborating Registry in the Registry Network? Registry Criteria
WHO CLINICAL TRIALS REGISTRY PLATFORM Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR From which countries will the Registry accept trials for registration? Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Is the Registry searchable over the Internet at no charge? Yes Yes Yes Yes Yes Yes ANZCTR ChiCTR CTRI ISRCTN NTR SLCTR Is the Registry open to all prospective registrants?
WHO CLINICAL TRIALS REGISTRY PLATFORM Partner Registries Partner Registries provide data to the Central Repository indirectly by establishing a relationship with a Primary Registry. Partner Registries need to meet the same criteria as a Primary Registry with the following exceptions:
Partner Registries do not need to be open to all prospective registrants. For example, they may be specific to a particular condition or intervention
Partner Registries do not need to have a national or regional remit or the support of government
Partner Registries do not need to be managed by a not-for-profit agency
Partner Registries do not need to meet the requirements of the ICMJE.
Physician Data Query
Trials on this registry are included on the WHO Search Portal via ClinicalTrials.gov , using the Protocol Registration System (PRS). ClinicalTrials.gov allows the registration of trials that:
are approved by a human subject review board (or equivalent) and
WHO CLINICAL TRIALS REGISTRY PLATFORM
conform to the regulations of the appropriate national health authorities.
Multi-site trials and multi-sponsor trials are susceptible to duplicate registration, thus care must be taken in how the trials are registered. For multi-sponsor trials it is the lead sponsor who should take responsibility for registration. ClinicalTrials.gov facilitates registration of trials in accordance with the International Committee of Medical Journal Editors (ICMJE) initiative requiring prior entry of clinical trials in a public registry as a condition for publication.
Account Application Process
Organizations and investigators wishing to register trials must first apply for a PRS account via the links to ClinicalTrials.gov. Within two business days, ClinicalTrials.gov will create the account and send email with instructions on how to login to the PRS, so that one can register trials.
There are two types of PRS accounts:
Organization accounts generally have multiple users and are used to register all the trials being conducted at an organization.
Individual accounts are used to register trials conducted by a single investigator.
European Leukemia Trial Registry This procedure, avoids double-registration in more than one register. The new Registry is bilingual (German/English), and provides short-protocols of ongoing German and European Leukemia Trials. The format of registry is given below:
WHO CLINICAL TRIALS REGISTRY PLATFORM Date of 1st enrolment* Target sample size* Phase Study type* Name of the study group Public title* Health Conditions studied* Full scientific study title* Secondary IDs* Date of registration* ELN-Study Number* Unique Trial Number* Interventions* Exclusion Criteria* Inclusion Criteria* Countries of recruitment* Contact for scientific queries* Contact for public queries* Contact person (s) in Study Center Aims Recruitment status* Age Stage
ABOUT BII - PROGRAMS OFFERED
Established in 2002, Bioinformatics Institute of India (BII), an initiative of Confrere Education Society, is a non profit making educational, R&D and development centre. It stands as a reputed and pioneering institution for imparting quality education and training in the different emerging disciplines of Life Sciences. BII is today recognized across the globe as a premier institution offering programs in the diverse areas of Bioinformatics, Clinical Trials, Pharma Regulatory affairs, Pharma Quality Assurance and Control, Drug Design and Patenting, IPR and Biotechnology etc.
SUBJECT AREAS OF SPECIALISATION BIOINFORMATICS CLINICAL TRIALS PHARMA REGULATORY AFFAIRS PHARMA QUALITY ASSURANCE AND CONTROL DRUG DESIGN AND PATENTING INTELLECTUAL PROPERTY RIGHTS BIOTECHNOLOGY
ABOUT BII – PROGRAMS OFFERED
These training programs are offered through various modes including distance participation, e-learning, classroom, etc. Workshops, Corporate trainings, etc. are also conducted from time to time. The quarterly journal Bioinformatics – Trends is one of its kind journal in India. The institute also supplies multimedia and corporate training kits to governments, private bodies and individuals in its diverse areas of expertise.
MODES OF TRAINING PROGRAMS DISTANCE PARTICIPATION CLASSROOM PROGRAMS CORPORATE TRAININGS PROJECTS/TRAININGS PUBLICATIONS E-LEARNING PROGRAMS WORKSHOPS
BII’s PROGRAMS IN CLINICAL TRIALS
INDUSTRY PROGRAM IN CLINICAL TRIALS, RESEARCH & ADMINISTRATION (12 MONTHS DISTANCE PARTICIPATION PROGRAM)
The prime objective of this program is to provide quality inputs in the area of Clinical Trial, Research & Administration, to working professionals and individuals who have completed their education and are willing to contribute to this area. It also aims to develop documentation/research writing expertise in the Clinical Trial, Research and Administration sector. Promotion of spread, enhancement and sharing of knowledge in this field is of great importance. The core areas of studies are comprised in the 8-Modules Course Structure: Module I- Clinical Trials Module II- Contract Research Module III- Contract Research and Clinical Trial Environment Module IV- ICH -GCP Guidelines - International Conference of Harmonisation Module V- ICMR -Guidelines on Biomedical Research on Human Subjects Module VI- SCHEDULE Y Module VII- Biostatistics Module VIII- Research Study Program Deliverables include : Training Kits comprising of Reference Materials and Free Lecture CDs, Support via Internet, Email & Telephone and Information exchange via BII Blog. Graduates/Final year students from any discipline can apply by downloading form and submitting it with BII Program Participation Fee of Rs.10,000(exam fee exclusive).
BII’s PROGRAMS IN CLINICAL TRIALS ADVANCE PROGRAM IN CLINICAL TRIALS, RESEARCH AND DATA MANAGEMENT (12 MONTHS CLASSROOM WEEKEND PROGRAM) The main objective of the course is to provide students with a theoretical and practical understanding of the issues, including ethical issues, involved in the design, conduct, analysis and interpretation of clinical trials.
After completion of the course, the participant would be able to:
Have better understanding of Good Clinical Practice (GCP) and Standard Operating Procedures for Clinical Research.
Participate in design, conduct and management of Global Clinical Trials, conducted at multicentric sites in India and Overseas.
Contribute more effectively in their profession - pharmaceutical/Bio pharmaceutical companies in drug development.
CRO's offering clinical research and clinical data management services, in BIO-IT Life science, Industry or Academic Research institutions.
As a clinical investigator at hospitals, medical sites conducting trials on subjects.
Handle regulatory affairs as per the changes in the statutory laws.
The core areas of studies are comprised in the 7-Modules Course Structure:
Module-I Clinical Trials and Clinical Trials Environment
Module-II Statistics for Clinical Trials
BII’s PROGRAMS IN CLINICAL TRIALS
ADVANCE PROGRAM IN CLINICAL TRIALS, RESEARCH AND DATA MANAGEMENT
(12 MONTHS CLASSROOM WEEKEND PROGRAM)
Module-III Clinical Data Management
Module-IV Contract Research
Module-V Regulatory Affairs, Good Clinical Practices, Pharmacovigilance and Ethics
Module-VI Practical Medical Writing and Documentation
Module-VII Research Study
The methodology for the program delivery would be:
Delivery of the lectures by the technically expertise Faculty.
Guest Faculty from industry and academia would deliver the lectures.
Along with the theoretical knowledge student would also get a chance to have a practical oriented understanding of the subject e.g. role of computers in Clinical Trials
E-learning platform via Moodle would also be employed for the classes.
Students would also be taken for Industrial and Hospitals’ visits to have an overview of the entire Clinical trial process.
Eligibility: The course is most suitable for doctors, medical professionals and pharmacists, although graduates/final year students from any discipline may also apply by submitting the application form with necessary fees and attachments.
BII’s PROGRAMS IN CLINICAL TRIALS The prime objective of this program is to help to understand basics of clinical trials. It has been specifically designed to answer scientific questions and to find better ways to treat individuals with a specific disease. The core areas of studies are comprised as follows: ONLINE PROGRAM IN CLINICAL TRIALS & RESEARCH (3 MONTHS e-LEARNING PROGRAM) Teaching and learning methods include content documents, directed reading, a range of on-line systems of information retrieval, literature reviews and moderated on-line seminars. Graduates in any discipline can apply . Highly motivated students pursuing graduation /Diplomas courses in Pharmaceutical science/chemistry and allied areas are also eligible . Course fee is INR 5000. Bioethics Clinical Trial Regulatory Affairs Clinical Trial Business Environment Clinical Trial Delivery Model Clinical Trial Team Clinical Trial Informatics Design of Experiments Bioavailability Studies Clinical Trial Statistics Patient Recruitment Good Clinical Trial Practices Features of Clinical Trials Basics of Clinical Trials & Clinical Research
THANK YOU For Further Details & Enquiries, Contact: Bioinformatics Institute of India C-56A / 28, Sector – 62 Noida – 2010301, U.P Tel: 0120-4320801/02 Mobile: 9818473366, 9810535368 Email: [email_address] Visit: www.bii.in