1. Addressing the innovation gap: strategies to inform treatment policies in low and middle income countries Shanthi Pal, WHO, Switzerland Sten Olsson, Uppsala Monitoring Centre, Sweden

2. WHO Global Programme for Safety Monitoring of Medicinal Products World Health Assembly Resolution 16.36 INVITES Member States to arrange for a systematic collection of information on serious adverse drug reactions observed during the development of a drug and, in particular, after its release for general use.

3. The full scope of pharmacovigilance (PV) The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems. ( The Importance of Pharmacovigilance, WHO 2002 ) By investing in PV, countries will benefit multifold: – Benefit harm assessment of medicines – Track SSFFC – Track irrational use – Track medication errors 3

4. Challenges to PV in low and middle income countries (LMIC) Lack of political support Lack of resources Lack of competence Lack of PV systems and/ or inadequate function Lack of communication and information exchange % Implemente d out of the total countries in the region % Implemente d (of those with data available) Number of Countries with Indicator Implemented Number of Countries with data available Number of Countrie s Group of countries 94 4548 A. Industrialized 133851339 B. Upper middle income 92951757 C1.Lower middle income 41221749C2.Low income Capacity to detect significant vaccine safety issue WHO survey of PV systems in 55 countries North America Europe

5. Why is this a problem? More than 300 products in the pipeline for neglected diseases, HIV AIDS, TB and malaria At least half of them will be launched in the coming years in those very settings where there is little or no capacity for post approval monitoring Developer Analysis, BVGH, 2012

6. Lead Optimization Preclinical Development GLP Tox. Phase IPhase IIPhase III Delamanid (OPC-67683) Gatifloxacin Moxifloxacin Rifapentine AZD5847 Bedaquiline (TMC-207) Linezolid Novel Regimens 2 PA-824 Rifapentine SQ-109 Sutezolid (PNU-100480) CPZEN-45 DC-159a Q201 SQ609 SQ641 Preclinical Development Discovery 1 Clinical Development Diarylquinoline DprE Inhibitors GyrB inhibitors InhA Inhibitors LeuRS Inhibitors MGyrX1 inhibitors Mycobacterial Gyrase Inhibitors Pyrazinamide Analogs Riminophenazines Ruthenium (II) complexes Spectinamides Translocase-1 Inhibitors Global TB Drug Pipeline Updated: June 18, 2012 BTZ043 TBA-354 www.newtbdrugs.org 4 Repurposed Drugs 6 New Drugs 3 New Classes Drugs currently in the regulatory review process

7. WHO Solutions: First build PV systems

8. Innovative solutions to support those systems Network of WHO Collaborating Centres (CC) to support PV systems in countries Uppsala Monitoring Centre, Sweden WHO CC Accra, Ghana WHO CC Rabat, Morocco WHO CC Oslo, Norway WHO CC Netherlands (Lareb) PV consultants in Africa, for Africa

9. Create a consortium plus 9 other partners

10. Dedicated resources

11. Innovative/ intuitive software for data management and information exchange ICH standards in ICH region and individual countries Lack of harmonization in other regions Data collected in LMIC not compatible with ICH standards Timely and accurate global exchange of PV information difficult Difficult to compare data across ICH and non ICH regions Vigiflow, E2b compatible data management tool WHO Solution for implementing ICH standards in non-ICH countries Both a reporting tool as well as a national database Can also support diverse MAH in LMIC

12. Vigiflow user countries in the world for receiving and storing ADR reports. The entered reports can be extracted as XML files can be transferred to other (E2b)databases A search and statistics module is built into the system Easy to use and error- checking ensures accuracy.

13. Results of this innovative approach LMIC are able to collect reports in standard format compatible with developed countries Information exchange between LMIC and global database now possible The software update and management occurs centrally, at Uppsala, Sweden Countries do not need to bother with self update of their tools Countries now have their own nationla database as well.

14. Impact of innovation Data from Africa pooled Part of global repository of ADRs Contribute to data mining First signal based on quality data of international standards – Amodiaquine-artesunate antimalarial medicine – Signal of Extrapyramidal symptoms from African PV data – Led to product information update by company

15. Innovations for broader use of PV data SSFFC: Substandard, Spurious, Falsified, Falsely-labelled and Counterfeit medicinal products (‘SSFFC’) Serious threat to patient safety and health systems globally Global threat, but LMIC particularly vulnerable Impact on medicines procured through global health initiatives

17. A novel algorithm To detect clusters of reports within the WHO Individual Case Safety Reports database - VigiBase™ – for lack of effect – based on geographic and temporal patterns – may reflect cases of SSFFC medicinal products To be tested in national databases – For prospective detection of SSFFC

18. Innovations to detect medication errors Reports of medication errors in WHO ICSR database PV system that : Records errors Analyses Learns Implements checks Prevents errors

19. Innovations to bring in additional stakeholders Patients as partners in pharmacovigilance – Faster identification of new medicine safety problems – Better understanding of impact of adverse drug reactions (ADRs) on life – More details of ADRs… – The full picture Need simple systems, to support reporting by patients

20. The ADR reporting tool for patients Developed by WHO and its partner, the UMC Complies with international standards (E2b format data entry) Language, style sheets, logos can be adapted to local preferences Can easily feed into the national database / PV centre

21. www.who.int/medicines/areas/quality_safety/safety_efficacy/en/index.html www.who.int/medicines/areas/quality_safety/safety_efficacy/en/index.html pvsupport@who.int Putting ideas to practice, in LMIC