1. www.tfda.or.tz 1 14 th ICDRA Singapore - 2 December 2010 Establishing a mechanism to avoid "shopping around" for ethical approval Fimbo, A. M Tanzania Food and Drugs Authority

2. www.tfda.or.tz 2 Outline ► EC/IRB shopping ► Mechanisms to avoid shopping ► Registration of clinical trials ► Establishing networks for sharing information: ► About AVAREF ► PACTA Project ► Tanzania experience

3. www.tfda.or.tz 3 EC/IRB shopping ► Is an act of applying for ethical or regulatory approvals from different ECs/IRBs/NRAs. ► Researchers who are not satisfied with one EC/IRB/NRA’s approvals/reviews switch over to another Authority which was not aware of the other's prior decision. ► Researchers would like to find the EC/NRA that's more likely to respond favourably to one's research proposal and circumvent those that might not or have more stringent requirements.

4. www.tfda.or.tz 4 EC/IRB shopping ► This can most often occur in countries with weak regulatory mechanism including minimal oversight of clinical trials. ► The review procedures may also be different in different settings. ► Trials banned in one country for safety and/or ethical reasons may be conducted in another country with weaker systems for overseeing trials. ► How to solve this

5. www.tfda.or.tz 5 Registration of trials (1) ► One way of solving the problem is to ensure that all trials are registered in a publicly accessible registry. ► A registry can help to identify publication bias such as when a trial is conducted but not published, often because there are adverse outcomes or results are ‘negative’. ► Ensures that objectives cannot be changed throughout the course of the trial. ► Can help to identify outcome bias if only a selection of the outcomes (usually those with positive results) are reported.

6. www.tfda.or.tz 6 Registration of trials (2) ► Registration also: ► Improves transparency and accountability of researchers. ► Ensures that key information is made available to the public and ► Enhance public trust in the conduct of clinical research.

7. www.tfda.or.tz 7 Registration of trials (3) ► Not reporting the results of trials is now increasingly seen as scientific and ethical misconduct. ► The pressure to register trials to reduce biased under-reporting is growing. ► Legislation in some countries now requires registration of trials, while some funding agencies and official bodies recommend it.

8. www.tfda.or.tz 8 Registration of trials (4) ► The 2004 Ministerial Summit on Health Research called on the WHO to establish “a network of international clinical trial registers to ensure a single point of access and the unambiguous identification of trials” ► The 58 th WHA endorsed the above call in 2005 ► This was also supported by the International Committee of Medical Journal Editors (ICMJE) ► In 2007 the ICMJE updated their statement - that they would only publish the results of trials registered prospectively and that members of the WHO Network of Primary Registries meet their requirements.

9. www.tfda.or.tz 9 Registration of trials (5) ► Trial registration is therefore mandatory for publication in medical journals according to ICMJE. ► Without a registration number from a WHO- endorsed primary registry, results of the trial will not even be considered for publication in member journals. ► The Declaration of Helsinki also requires clinical trials to be registered in a publicly accessible database before recruitment of the first subject (Declaration of Helsinki, WMA 2008).

10. www.tfda.or.tz 10 Registration of trials (6) ► The International Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/) is a global initiative that was established by WHO in 2006 in response to demand from countries through the WHA.http://www.who.int/ictrp/en/ ► The aim of ICTRP is: ► To make information about all clinical trials involving human beings publicly available. ► To provide a forum for registers to exchange information and work together to establish best practice for clinical trial registration. ► To link clinical trials registers in order to ensure a single point of access and the unambiguous identification of trials with a view of enhancing access to information by patients, families, patient groups and others (WHA 2005).

11. www.tfda.or.tz 11 Registration of trials (7) ► Primary Registries in the WHO Registry Network include: ► Pan African Clinical Trial Registry (PACTR) ► Australian New Zealand Clinical Trials Registry (ANZCTR) ► Clinical Trials Registry - India (CTRI) ► German Clinical Trials Register (DRKS) ► The Netherlands National Trial Register (NTR) ► Sri Lanka Clinical Trials Registry (SLCTR) ► www. ISRCTN.org ► Chinese Clinical Trial Registry (ChiCTR) ► Clinical Research Information Service (CRiS), Republic of Korea ► Iranian Registry of Clinical Trials (IRCT) ► Japan Primary Registries Network (JPRN) (http://www.who.int/ictrp/network/primary/en/index.html):http://www.who.int/ictrp/network/primary/en/index.html

12. www.tfda.or.tz 12 Registration of trials (8) ► Despite all the efforts, there are still some challenges on achieving universal trial registration. ► It is believed that many trials are still conducted/have been conducted without being registered (particularly in poor countries where resources are limited in scrutinizing and confirming whether trials have been registered or not). ► This can also be explained by the fact that trial registration is not a legal requirement and lacks enough power of enforcement. ► Having legislation in place can help to ensure that all researchers register their trials. ► What has been done in Africa?

13. www.tfda.or.tz 13 AVAREF (1) ► Taking into account the challenges facing Africa in overseeing clinical trials including issues related to registration of trials and recognizing the strength of networking amongst ECs & NRAs, the African Vaccine Regulatory Forum (AVAREF) was established during the NRA workshop organized by WHO in Accra – Ghana in Sept 2006. ► AVAREF has ever since been an informal network approach to regulation of clinical trials in Africa. ► The Forum is made up of 19 countries at the moment: Botswana, Burkina Faso, Cameroon, Ethiopia, Kenya, Gambia, Ghana, Gabon, Uganda, Tanzania, Mali, Malawi, Nigeria, South Africa, Senegal, Rwanda, Mozambique, Zambia and Zimbabwe ► More countries are invited to join the Forum at any time.

14. www.tfda.or.tz 14 AVAREF (2) ► Has been an effective initiative to stimulate progress towards regulatory harmonization of clinical trials ► It serves as an "ad-hoc" scientific and regulatory advisory body for ECs/NRAs to make informed decisions regarding evaluation of registration dossiers, authorization of clinical trials of vaccines in the region.

15. www.tfda.or.tz 15 AVAREF (3) ► The Forum meets every year: ► AVAREF 1 – Accra, Ghana – 2006 (inception) ► AVAREF 2 – Ouagadougou, B/Faso - 2007 ► AVAREF 3 – Zanzibar, Tanzania - 2008 ► AVAREF 4 – Abuja, Nigeria - 2009 ► AVAREF 5 – Nairobi, Kenya - 2010 ► AVAREF 6 – Planned for either Mozambique, Zimbabwe, Malawi or Senegal - 2011

16. www.tfda.or.tz 16 Objectives of AVAREF ► To provide information to countries targeted for clinical trials of vaccines, on vaccine candidates and timelines. ► To promote communication and collaboration between NRAs in countries where vaccines are developed and ECs and NRAs in countries targeted for clinical trials. ► To provide expertise to African NRAs, especially, on development of procedures for authorization and monitoring of clinical trials as well as the evaluation of data. ► To promote vaccine development and access, in line with the Global Immunization and Strategy and Vision (GIVS), as well as the goals of the IVB/HQ and IVD/AFRO programmes.

17. www.tfda.or.tz 17 Major achievements ► Joint reviews and joint inspections conducted (Conjugate meningitis A and Malaria vaccines) ► Development of African Common Clinical Trial Guidelines (ACCTG) ► Integration of ethical review, regulation and registration of clinical trials

18. www.tfda.or.tz 18 Major achievements ► Model regulatory procedures developed and adopted by many countries ► Regulatory oversight has improved significantly in region ► Channels of communication among African regulators and with regulators from developed countries have created confidence, strength and willingness to harmonize processes

19. www.tfda.or.tz 19 PACTA Project (1) ► As part of AVAREF initiative a working group of Pan African Clinical Trials Alliance (PACTA) has been established. ► The working group consists of 6 countries (Tanzania, Uganda, Nigeria, South Africa, B/Faso and Ghana). ► The aims of the working group is to push forward some of the agenda items agreed during AVAREF meetings to include:

20. www.tfda.or.tz 20 PACTA Project (2) ► Establishing a more effective coordination between NRAs and ECs ► Processes/Models for authorization of clinical trials ► Registration of clinical trials ► The working group held its first meeting at WHO HQ in Geneva 9 – 10 th Nov, 2010 ► The issues above were agreed to be piloted in the countries participated and results will be reported during the forthcoming AVAREF meeting. ► A timeline of 3 & 6 months have been agreed for countries to provide feedback on progress.

21. www.tfda.or.tz 21 Tanzania experience (1) ► The TFDA has been active in setting up a system for regulation of clinical trials since 2003. ► Standards - documents, processes and procedures related to oversight of clinical trials have been developed ► The Authority assesses and approves applications to conduct clinical trials in TZ ► Ensures that investigational products meets appropriate standards of quality, safety and efficacy with due regard to the phase of the trial

22. www.tfda.or.tz 22 Tanzania experience (2) ► Ensures that clinical trials are appropriately designed to meet stated objectives according to national laws and regulations ► Ensures that clinical trials are conducted in accordance with existing national laws/regulations or internationally accepted standards e.g. WHO, ICH-GCP etc. ► Conducts inspections at investigator sites and/or sponsor/CRO facilities

23. www.tfda.or.tz 23 Tanzania experience (3) ► Regulations (The Tanzania Food, Drugs and Cosmetics (Clinical Trials Control) Regulations, 2009) which provides for registration of clinical trials are in final stages of approval. ► A National Registry is in final stages of development.

24. www.tfda.or.tz 24 Tanzania Clinical Trial Registry http://www.tfda.or.tz/clinical/index.php#

25. www.tfda.or.tz 25 Tanzania Clinical Trial Registry http://www.tfda.or.tz/clinical/index.php#

26. www.tfda.or.tz 26 TzCTR

27. www.tfda.or.tz 27 Conclusion ► Registration of clinical trials allows for researchers and the public to know what studies are being conducted, by whom and where ► Ensures research participants are not exposed to unnecessary risks ► Permits human research to be done with public scrutiny ► Reduces shopping around for EC/NRA approvals ► AVAREF has been a good platform towards harmonization, capacity building and sharing of information to include trials being carried out in Africa.