4, 5 2 7 1 1, 8 1 9 - DNDi Leish 201… · informed consent & pharmacovigilance: Hajipur, Vaishali,...

World Leish 2013 Together for Impact

TRANSLATION FROM WHO RECOMMENDATION TO IMPLEMENTATION INTO

NATIONAL POLICY Ellis S1 Musa A2 Burza S3 Alirol E4 5 Lima M A3 Chappuis F4 5 Hailu A6 Khalil E2 Olobo J7 Strub N1 Wasunna M1 8 Sharma B1 Balasegaram M9 Author Affiliation 1Drugs for Neglected Diseases initiative Switzerland 2 Institute of Endemic Diseases University of Khartoum Sudan 3Meacutedicos Sin Frontieras Spain Hocircpitaux Universitaires de Genegraveve Switzerland Meacutedecins Sans Frontiegraveres Switzerland 6Addis Ababa University School of Medicine Ethiopia 7Makerere University Uganda 8Kenya Medical Research Institute Nairobi 9MSF Access Campaign Switzerland

Phase III Policy Implementation 2

India - Phase III Clinical trial efficacy

AmB SD Ampho B Ampho B AmB+M AmB+PM M+PM

ITT 304 108 157 160 157 158

Cure at M6

291 957

104 963

146 930

156 975

153 975

155 987

PP 304 106 156 158 155 158

Cure at M6

291 957

104 981

146 936

155 981

153 987

156 987

SourceSundar S Chakravarty J Agarwal D Rai M Murray HW Single-dose liposomal amphotericin B for visceral leishmaniasis in India N Engl J Med 2010 Feb 11362(6)504-12

S Sundar study VL Combo study

Source Sundar S Sinha PK Rai M Verma DK Nawin K Alam S Chakravarty J Vaillant M Verma N Pandey K et al Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India an open-label non-inferiority randomised controlled trial Lancet 2011 377(9764)477-486

3

3

Clinical Trial ldquoReal liferdquo

Photo DNDi DNDi and Catherine Royce Photo DNDi DNDi and sally Ellis

4

India

All drugs are registered VL Treatments in use

WHO Recommendation

No published data in Primary Health Care Setting Implementation plan conducted in PHC to evaluate

treatments in a wider patient population in Bihar India bull Assess the effectiveness bull Evaluate the safety profile bull Assess if there are any important adverse outcomes

in specific patient groups

Combination AmB 5mgkg on D1 + MF D 2-8 MF + PM Day 1-10 AmB 5mgkg on D1 + PM D 2-11

Single dose AmB 10mgkg on D 1

Miltefosine monotherapy 28 days conventional Amphotericin B up to 30 days

5

Project Implementation with Partners

Key Implementing Partners State Health Society Bihar All the Doctors and

supporting staff from Government working at the District Hospital and PHCs

Rajendra Memorial Research Institute Patna as site and training support

Meacutedecins Sans Frontiegraveres partners in Vaishali district

LSHTM ITM-Antwerp

6

Sites participating in VL PV 001

Saran bull District Hospital Chhapra bull PHCs Maraurah Dariyapur

Baniyapur and Parsa

Vaishali bull District Hospital Hajipur bull PHCs Vaishali Garaul Mahua

Raghopur and Mahnar

7

Treatments

PHC District Hospital Referral centre

Sites 1-2 sites eg District Hospital

Milt + PM for 10 d

5+ PHC 5+ PHC

AmB (5) + Milt for 7d

Referral Centres (special cases)

SDA

Other VL treatments if SDA contraindicated

10-15 PHCs in 2-3 districts in Bihar eg Vaishali Saran

Project Design

Open label prospective non randomised non comparative multicentre observational study assessing safety amp effectiveness of new treatment

Sample Size Safety 2000 patients - 86 probability and 3000 patients - 95 probability that 1 ADR will be detected (expected incidence of 11000) Effectiveness 300 patients treated a failure risk of 5 could be estimated with at least 5 precision

8

Key components of the project

Step 1- initial piloting Step 2 ndash consolidationreporting bull Active monitoring amp evaluation bull Surveillance register bull Safety (PV) bull Treatment Compliance Duration 1-2 years Sites 1-2 District hospitals and 10+ PHCs No of patients At least 1000 (300 per treatment) Follow up 6 amp 12 month follow up visit for efficacy

Data review

bull Continue Surveillance register bull Continue PV Duration 2-3 years Sites Potential for implementation in other endemic areas by NCP and SHS No of patients approximately 6000 bull 6 monthly PUR bull Long term reporting of AEs will be

handed over to the NPP

9

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600

Aug 12 Sep Oct Nov Dec Jan Feb Mar Apr

Recruitment Pilot Study

Total SDA Total A+M Total P+M Total Recruited

SNo Dates Training Venue Participants

1 7-10 Dec 2011 MSF Team- study protocol amp GCP

informed consent amp pharmacovigilance Hajipur Vaishali Bihar 42

2 30-31 Jan 2012 Medical professional of PHCs Allopathic doctors and AYUSH

ANM Training school Chappra Saran Bihar

75

3 9-10 April 2012 Sadar hospital Hajipur

Vaishali 49

4 24-25 May 2012 GCP Training Saran (24) amp Vaishali (25) 42 + 38

Classifications Number of Patients

Paediatric patient lt12 130 Severe disease 3

Severely Malnourished 4 TB +ve 1

Age less than 2 years 0 Pregnant 0 HIV +ve 9 PKDL 1

10

East Africa Kenya Sudan amp Ethiopia Uganda

WHO Recommendation

SSG amp PM Combination 17 Days

Country Recommendation

Revised Guidelines launched

Guidelines revised but not launched

SSG Registration status

Registered- Nov 08 Not registered Registered 2009

PM Registration status

Registered - Feb 13 Submitted Registered ndash Jan 2012

Project Objectives bull Monitor SSGampPM safety bull Identify additional risks that have not been reported during clinical studies bull To determine if ADR are increased in specific groups of patients bull Monitor the treatment failure rate bull Monitor any evidence in regional variation in terms of effectiveness amp safety

11

11

Sites Ethiopia Sudan Kenya Uganda

Country Study Coordinator

KEMRI Data Centre TCC

Steering Committee

1 Data review and collection 2 SAE 3 Supplies

1 Data Management 2 Coding 3 Report preparation

1 Safety review 2 Periodic update report

Project Design

bull Prospective bull Open label bull Multicentre bull Observational bull Pharmacovigilance bull Effectiveness

12

Participating Sites in SSGampPM Sudan 1 Kassab Hospital - IED 2 Prof El Hassan Centre for

Tropical Disease Doka 3 Tabarakallah - MSF 4 Um el Kehr ndash MoH 5 Bazura ndash MoH 6 Elhawata ndash MOH Kenya 7 Kimalel - KEMRI 8 Kacheliba ndash MSF MoHDNDi Ethiopia 9 Gondar University Hospital 10 Abdurafi 11 Arba Minch Hospital Uganda 12 Amudat Hospital

1 2

3

4 6

5

12

11

8 7

9

10

13

Challenges to consider Registration status ndash required for implementation EC and RA Approval Process Requirements for collecting additional data

Clinical trial or not Efficacy safety or both Special populations - young children pregnant women etc Patient registries eg pregnancy registry Feasibility of new treatments in resource limited setting

Revising amp Implementing national treatment guidelines Status of National Pharmacovigilance program Collecting data in busy health centres hospitals Training health care workers

15

ACKNOWLEDGEMENTS All our patients East Africa Site teams Kassab Hospital and Prof El Hassan Centre for Tropical Disease Doka IED Sudan Tabarakallah ndash MSF Um el Kehr

Bazura Elhawata Ministry of Health Sudan Kimalel ndash KEMRI Kacheliba ndash MSF MoHDNDi Gondar University Hospital Abdurafi Arba Minch Hospital Ethiopia Amudat Hospital Uganda

Team Clelia BardonneauRobert Kimutai Raymond Omollo Godfrey Nyakaya Peninah Menza Michael Ochieng Truphosa Omollo LEAP Universities of Khartoum Addis Ababa University Gondar University Makerere Kenya Medical Research Institute Ministries

of Health of Kenya Uganda Ethiopia and Sudan LSHampTM MSF I+ Solutions Donors Meacutedecins Sans FrontiegraveresDoctors without Borders International Spanish Agency for International Development

Cooperation (AECID) Spain Swiss Agency for Development and Cooperation (SDC) Dutch Ministry of Foreign Affairs (DGIS) The Netherlands Federal Ministry of Education amp Research (BMBF) through KfW Germany Pro Victimis Switzerland Medicor Foundation Liechenstein

India Site teams Hajipur amp Chhapra District Hospitals and Parsa Marhaura Dariyapur Baniapur Goraul Mahnar Mahua Raghopur amp

Vaishalli PHCs Team Nathalie Strub Vishal Goyal Abhijit Sharma Pankaj Kumar Muhammad Akram Raj Kishore Rai Anurag Singh Partners Bihar State Health Society MSF Rajendra Memorial Research Institute OWH PATH WHO-TDR Donors Bill amp Melinda Gates Foundation Department for International Development (DFID) UK Meacutedecins Sans FrontiegraveresDoctors

without Borders Spanish Agency for International Development Cooperation (AECID) Swiss Agency for Development and Cooperation (SDC) Starr International Foundation Switzerland Other private foundations amp private individual donors

16

Slide Number 1

Phase III Policy Implementation



India



Slide Number 8


Status - India

East Africa

Slide Number 12

Participating Sites in SSGampPM

Status

Challenges to consider

ACKNOWLEDGEMENTS

Phase III Policy Implementation 2



ITT 304 108 157 160 157 158

Cure at M6

291 957

104 963

146 930

156 975

153 975

155 987

PP 304 106 156 158 155 158

Cure at M6

291 957

104 981

146 936

155 981

153 987

156 987




3

3



4

India


WHO Recommendation







5






LSHTM ITM-Antwerp

6



Baniyapur and Parsa


Raghopur and Mahnar

7

Treatments



Milt + PM for 10 d

5+ PHC 5+ PHC



SDA



Project Design



8



Data review



9

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600









75


Vaishali 49






10


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS



ITT 304 108 157 160 157 158

Cure at M6

291 957

104 963

146 930

156 975

153 975

155 987

PP 304 106 156 158 155 158

Cure at M6

291 957

104 981

146 936

155 981

153 987

156 987




3

3



4

India


WHO Recommendation







5






LSHTM ITM-Antwerp

6



Baniyapur and Parsa


Raghopur and Mahnar

7

Treatments



Milt + PM for 10 d

5+ PHC 5+ PHC



SDA



Project Design



8



Data review



9

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600









75


Vaishali 49






10


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS



4

India


WHO Recommendation







5






LSHTM ITM-Antwerp

6



Baniyapur and Parsa


Raghopur and Mahnar

7

Treatments



Milt + PM for 10 d

5+ PHC 5+ PHC



SDA



Project Design



8



Data review



9

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600









75


Vaishali 49






10


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS

India


WHO Recommendation







5






LSHTM ITM-Antwerp

6



Baniyapur and Parsa


Raghopur and Mahnar

7

Treatments



Milt + PM for 10 d

5+ PHC 5+ PHC



SDA



Project Design



8



Data review



9

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600









75


Vaishali 49






10


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS






LSHTM ITM-Antwerp

6



Baniyapur and Parsa


Raghopur and Mahnar

7

Treatments



Milt + PM for 10 d

5+ PHC 5+ PHC



SDA



Project Design



8



Data review



9

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600









75


Vaishali 49






10


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS



Baniyapur and Parsa


Raghopur and Mahnar

7

Treatments



Milt + PM for 10 d

5+ PHC 5+ PHC



SDA



Project Design



8



Data review



9

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600









75


Vaishali 49






10


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS

Treatments



Milt + PM for 10 d

5+ PHC 5+ PHC



SDA



Project Design



8



Data review



9

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600









75


Vaishali 49






10


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS



Data review



9

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600









75


Vaishali 49






10


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS

Status - India

28

92 140

190

250 306

395

465 495

0

100

200

300

400

500

600









75


Vaishali 49






10


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS


WHO Recommendation










11

11




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS




Steering Committee




Project Design


12



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS



1 2

3

4 6

5

12

11

8 7

9

10

13




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS




15









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS









16

Slide Number 1




India



Slide Number 8


Status - India

East Africa

Slide Number 12


Status


ACKNOWLEDGEMENTS

4, 5 2 7 1 1, 8 1 9 - DNDi Leish 201… · informed consent & pharmacovigilance: Hajipur, Vaishali,...

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Transcript of 4, 5 2 7 1 1, 8 1 9 - DNDi Leish 201… · informed consent & pharmacovigilance: Hajipur, Vaishali,...