Meeting Report PV workshop Hanoi 12-14 November 2014 final

Inter‐regional workshop on

pharmacovigilance for new drugs and

novel regimens for the treatment of

drug‐resistant tuberculosis

MeetingReport

12 – 14 November 2014

Hanoi, Viet Nam

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WHO/HTM/TB/2015.07

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Abbreviations

ADR Adverse drug reactions

AE Adverse event

ANRS National Agency for the Research on AIDS and Hepatitis ‐ France

US CDC Centre for Disease Control and Prevention of United States of America

CTCAE Common Terminology Criteria for Adverse Events

DAIDS Division of AIDS (of the National Institute of Allergy and Infectious Diseases)

DR‐TB Drug‐resistant TB

EMP Essential Medicines and Pharmaceutical Policies

GTB Global TB Programme

IRD Interactive Research and Development

MDR‐TB Multidrug‐resistant TB

MedDRA Medical Dictionary for Regulatory Activities

MSF Médecins Sans Frontières

MSH Management Sciences for Health

NPV National PV centre

NTP National TB Programme

PIH Partners Iin Health

PMDT Programmatic management of drug‐resistant TB

PV Pharmacovigilance

SAV Safety and Vigilance

SIAPS Systems for Improved Access to Pharmaceuticals and Services

TB/HIV HIV‐infected TB

UMC The Uppsala Monitoring Centre

USAID United States Agency for International Development

WG Working group

WHO World Health Organization

WHO‐ART WHO Adverse Reaction Terminology

WPRO WHO Western Pacific Regional Office

XDR‐TB Extensively drug‐resistant TB

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Contents

Abbreviations .......................................................................................................................................... 2

Background and rationale ....................................................................................................................... 4

Objectives & expected outcomes ........................................................................................................... 5

Participation ............................................................................................................................................ 5

Presentations .......................................................................................................................................... 6

Working Group discussions ..................................................................................................................... 8

WG1. Collection and management of CEM data ............................................................................ 8

WG2. Analysis, sharing and communication of CEM data .............................................................. 9

WG3. Responsibilities of different stakeholders in PV support ...................................................... 9

Next steps for the joint plan for the collection and analysis of safety data ......................................... 11

Tables .................................................................................................................................................... 12

Table 1: Data collection for active pharmacovigilance in TB patients ......................................... 12

Table 2: Proposed minimum programmatic indicators for pharmacovigilance for TB ................. 21

Table 3: Elements for a summary profile of drug safety / toxicity ............................................... 24

Table 4: Roles and responsibilities of partners for cohort event monitoring for TB .................... 25

Acknowledgement ................................................................................................................................ 26

References ............................................................................................................................................ 26

Annex 1: Agenda of the meeting .......................................................................................................... 28

Annex 2: List of participants ................................................................................................................. 31

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Backgroundandrationale

Pharmacovigilance (PV), defined by the World Health Organization (WHO) as “the science and

activities relating to the detection, assessment, understanding and prevention of adverse effects or

any other drug‐related problem” (1) is a core component of the pharmaceutical management system,

and represents an arm of patient care.

In many countries, the notification of adverse drug reactions (ADRs) to any medicines, including anti‐

TB drugs, is normally in the form of spontaneous reporting. While this is considered the most

common form of PV that all countries should have, it is not an active measure to look for and report

all adverse events and safety concerns when the risk of harm related to medicines is high, especially

when treatment regimens are complicated or limited experience exists with the use of certain

medicines in particular patient subgroups. Such is the case today for patients with multidrug‐

resistant TB (MDR‐TB), especially when patients receive treatment with regimens based on new (e.g.

bedaquiline or delamanid) and repurposed (e.g. linezolid, clofazimine) drugs. Under such

circumstances, active PV techniques, such as Cohort Event Monitoring (CEM), can monitor patient

safety in a more rigorous and systematic manner, as recommended in the WHO interim policies for

the use of bedaquiline and delamanid. (2, 3, 4) Some countries are currently introducing CEM within

the monitoring framework of TB patients, such as in Belarus where CEM has been used since 2013 to

monitor the HIV‐infected TB (TB/HIV) patients on anti‐TB and antiretroviral medication. A number of

partners are supporting these efforts in several countries, including KNCV‐Tuberculosis Foundation,

Médecins Sans Frontières (MSF), Partners In Health (PIH), the UNION, and US CDC. In addition, the

USAID‐funded project Systems for Improved Access to Pharmaceuticals and Services (SIAPS) of

Management Sciences for Health (MSH) is promoting PV and safe drug use in a number of countries

and settings.

The “Inter‐regional workshop on PV for new drugs and novel regimens for the treatment of drug‐

resistant tuberculosis” was organised jointly by WHO/HQ (Essential Medicines and Pharmaceutical

Policies (EMP), the Global TB Programme (GTB)), the Regional Office for the Western Pacific of WHO

(WPRO), and the WHO Representative Office in Viet Nam with the support of USAID and UNITAID.

The meeting objectives fit within the framework of assistance being provided to national TB

programmes (NTPs) to strengthen their PV systems in accordance with WHO policies and ensure that

patient safety is effectively monitored during treatment of MDR‐TB with new drugs and novel

regimens. (3, 4, 5, 6) Currently NTPs are operating in a rapidly changing context, with the

introduction of novel regimens and new anti‐TB drugs which are entering the market ahead of the

completion of Phase III trials. Limited knowledge about the risks and effectiveness of these

interventions makes the close monitoring of the treatment more important. Effective PV at a

national level will require close collaboration and a clear definition of roles between the government

structure responsible for PV (national PV centres), the NTP, non‐programme health care providers,

technical partners, and donors. The workshop brought representatives of all these stakeholders

together to discuss how this can be effectively implemented.

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Objectives&expectedoutcomes

The agenda (Annex 1) was developed in order that the following specific meeting objectives could be

addressed:

1) updates provided to the participants on (i) WHO policies and (ii) partner and country activities on

PV of patients treated with new drugs and new regimens for MDR‐TB;

2) discussion held between stakeholders on the different methods required for the collection of

CEM data during the treatment of MDR‐TB patients (organization, criteria, data variables and

definitions, classification of severity and seriousness, laboratory and other tests, monitoring

frequency, adaptation of paper and electronic systems);

3) discussion held between stakeholders on the different methodologies required for the analysis

and communication of CEM data relating to the treatment of MDR‐TB patients (organization,

indicators, detection of signals, inference of causality, messaging and sharing of findings); and

4) discussion held on the roles and responsibilities of different stakeholders in supporting countries

to reinforce PV when introducing new and repurposed TB drugs and novel regimens (including

technical assistance, financial support and resource mobilization, coordination, organization,

advocacy)

The outcomes at the end of the meeting were the following:

1) workshop participants were updated on WHO policies related to PV in the treatment of MDR‐TB;

2) agreement was reached between stakeholders to work more closely on the harmonization of

methods for the collection, sharing, analysis, interpretation and communication of information in

CEM of MDR‐TB patients; and

3) a joint plan for the collection and the analysis of safety data for new drugs and shorter regimens

was outlined.

Participation

The participants (Annex 2) included staff from national Ministries of Health of high MDR‐TB burden

countries (plus Lao PDR) which are using, or will shortly introduce, new and repurposed drugs and

novel regimens for MDR‐TB patients, namely: Bangladesh, Belarus, Indonesia, Kazakhstan, Lao PDR,

Myanmar, Thailand, Viet Nam, the Philippines, and South Africa. The participants included officials

responsible for MDR−TB care within the NTPs and for PV in the Ministry of Health or National Drug

Regulatory Authority. There were also representatives of the main TB technical and funding partners

(Action Damien, Global Fund, IRD, KNCV, MSH/SIAPS, MSF, the UNION, US CDC, and USAID),

WHO/HQ (SAV, GTB), WHO/WPRO and WHO Country Offices. Representatives of the WHO

Collaborating Centre for PV in Rabat, Morocco and the Nigerian National Agency for Food and Drug

Administration and Control also attended.

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Presentations

The meeting consisted of formal presentations and discussions in groups. Most of the participants

had also taken part in a preceding 2‐day meeting between 10 and 11 November at the same venue

dealing with preparation for the introduction of new TB drugs based on WHO policy.

On 12 November, the participants were welcomed by the NTP and introduced to the meeting

objectives and documents. Following this there were a series of presentations highlighting the status

of the global response to MDR‐TB and policies on MDR‐TB care, and on the principles of PV and

cohort event monitoring as they apply to TB. This was followed by presentations of diverse country

experiences in the safety monitoring for patients affected by TB, TB/HIV and MDR‐TB in 4 countries

(Bangladesh, Belarus, Niger and Viet Nam). Highlights of these presentations were as follows:

MDR‐TB: global response and WHO policies

Ernesto Jaramillo, of WHO Global TB Programme, presented the vision, goals and targets of the new

WHO End TB Strategy for prevention, care and control after 2015; the process adopted by WHO for

developing policies and guidelines; and the rationale for the recommendations on PV in treatment of

DR‐TB with bedaquiline or delamanid, or shorter regimens with repurposed drugs. Goal, objectives

and expected outcomes of the meeting were presented.

Active pharmacovigilance: rationale & methods

Svetlana Setkina, of the Belarus Centre for Examinations and Tests in Health Service, discussed the

position and added value of active PV within the context of newly introduced drugs and non‐

standard regimens, a situation which is now very relevant for MDR‐TB care. She described the

relative advantages and disadvantages of active PV versus other forms of surveillance for drug‐

related harms.

Principles of cohort event monitoring (CEM)

Comfort Suku, from the Nigerian National Agency For Food And Drug Administration And Control,

next presented cohort event monitoring (CEM), a methodology of active PV structured around a

prospective, observational cohort study design for adverse events associated with one or more

medicines. These studies aim to quantify and characterize risk of exposures over the shortest

possible time. She described the methods that have been used to organize these studies under field

conditions in both high and low income settings.

Safety monitoring in TB & HIV patients in Belarus

Svetlana Setkina presented the work that her centre has been doing in collaboration with Alena

Skrahina, of the Belarus Republican Centre of Pulmonology & TB, to mount CEM for TB/HIV patients

on treatment with antiretrovirals since 2013. Standard forms have been developed to capture data

on adverse events and laboratory test results at start of treatment and at specific time points in the

course of therapy. The findings of the study are expected to be summarised shortly.

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Safety monitoring in TB & MDR‐TB patients in Viet Nam

Nguyen Hoang Anh, of the Viet Nam National Centre of Drug Information and Adverse Drug

Reactions Monitoring (DI and ADR centre), presented the PV system and safety monitoring for TB

and MDR‐TB patients in Viet Nam. The spontaneous reporting has been implemented over last 20

years for safety monitoring of all patients including TB and MDR‐TB. A Global Fund supported project

on cohort event monitoring (CEM) for MDR‐TB patients has been implemented in nine MDR‐TB

treatment centres in close collaboration between the NTP and the DI and ADR Centre. A scale‐up

plan has been developed for CEM for pre‐XDR/XDR‐TB patients who will be enrolled on treatment

with bedaquiline if the implementation plan has been approved by the national authorities.

Safety monitoring for shorter regimens in Bangladesh and Niger

Alberto Piubello, of Action Damien, presented safety monitoring for patients who receive shorter

regimens for treatment of MDR‐TB in Niger and Bangladesh. In Niger, a patient ADR card and severe

ADR form have been developed and used for collection of safety data for MDR‐TB patients on

shorter regimen. Electronic ADR databases (e.g. Excel, EpiData) have been developed for

management of ADR data. The severity of adverse events is graded using the scale of National

Agency for the Research on AIDS and Hepatitis ‐ France (ANRS). Frequency of different ADRs was

reported for patients on shorter regimens in Niger and Bangladesh.

Principles of causality assessment

Raja Benkirane, of Moroccan Pharmacovigilance Centre, made a presentation on principles, criteria,

approaches and methods of causality assessment. WHO method and case studies of causality

assessment based on criteria and likelihood categories, and data elements required for causality

assessment were also presented.

Data collection and analysis for CEM of MDR‐TB patients

Svetlana Setkina presented data collection and analysis for CEM of MDR‐TB patients. The

presentation included essential elements and tools for CEM data collection, CEM database, data

analysis, signal management, challenges and possibilities of data analysis in CEM. Belarus CEM

examples were also presented.

“Expecting the worst”: Anticipating, preventing and managing medicinal product crises

Bruce Hugman, a consultant on communications for Uppsala Monitoring Centre, a WHO

Collaborating Centre for Pharmacovigilance, made a presentation on the importance and the

essential principles of crisis management as they would apply within a context of introduction of

new drugs and novel regimens for TB. The point of departure is that few disasters are completely

unexpected and contingency may be made beforehand to pre‐empt or reduce the damage. A

number of examples were analysed in which antecedent conditions had led to avoidable damage,

such as ignoring early signs of trouble (at times weak ones), hierarchy “deafness” to front line

intelligence, failure to anticipate obstacles (social, religious, historical, political), lack of transparency

and consent, and lack of engagement with community. For the new TB drugs, one may anticipate

that there may be community hostility/withdrawal, rumours about the purposes/ethics of the

program and the quality of the medications, programmatic errors more likely when dealing with an

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unfamiliar intervention, unrealistic expectations of the new drugs, outrage/suspicions at serious

ADRs or deaths, unknown/unexpected events and adherence. Preventing crisis demands assessing

all the known risks and putting risk management processes in place to reduce or eliminate them.

Crisis planning demands anticipating the worst, known and unknown, and having active plans to

implement the moment anything serious goes wrong. The planning needs to have communications

roles and functions in place; risks assessed in every aspect and at every stage of program planning

and implementation; every member of team aware of importance of early signals of trouble,

however weak; every member of team informed about and rehearsed in exactly what to do when

something goes wrong; and constant review and recalibration of plans. In the face of a negative

episode, there needs to be a rapid, empathetic communications with all parties are critical to least

negative outcomes; there must be open lines of communication from the front‐line to program

managers; defensiveness, denial, evasion are counterproductive; a crisis management plan must be

constantly discussed and reviewed; and a crisis should be an opportunity for review, learning and

change.

Ethical issues in PV of TB

The presentation focused on the rationale for ethics as they apply specifically to PV. PV is largely a

surveillance activity and therefore a number of ethical issues in surveillance also apply to PV, such as

what is the justification for public health surveillance? Is there an obligation to use surveillance data

for a public health intervention? What is the obligation of the researcher? Is it enough to just make

data available or does the researcher have to ensure data to be used? To what extent do the results

of surveillance have to be communicated to the subjects? How is confidentiality respected? In

conclusion, WHO’s recommendation on the handling of ethics of surveillance is currently under

review. Ethics review of surveillance protocols should be deferred to countries, as per local practice

or law. Likewise, CEM protocols can benefit from the review by a national ethics committee, but

enrolling of patients on treatment and implementation of the CEM protocol should not

unnecessarily be delayed until the outcome of the review is available.

WorkingGroupdiscussions

In Day 2 and Day 3 of the Inter‐regional workshop the participants gathered in three working groups

(WG) to discuss around the main thematic objectives of the meeting, respectively the different

methods required for the collection of CEM data during the treatment of MDR‐TB patients (WG1);

the analysis and communication of CEM data relating to the treatment of MDR‐TB patients (WG2);

and the roles and responsibilities of different stakeholders in supporting countries to reinforce PV

when introducing new and repurposed TB drugs and novel regimens (WG3).

WG1.CollectionandmanagementofCEMdata

This working group was led by CDC and MSH teams. The group focused on the required elements of

the data collection for CEM for TB as well as prioritization of data elements into essential and

optional categories to avoid overburden of staff at treatment centres on data collection. The

working group also discussed the structure of the data collection forms and the organization of data

to be collected at a single time point and data to be regularly collected during the treatment course,

of the data on effectiveness of treatment and data on safety. The group also examined different

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scales and grading systems for classification of severity and seriousness of adverse events. Logistics

of data collection e.g. paper‐based and electronic data collection systems, frequency of data

collection and monitoring, data entry and data management were discussed. One of the results from

the working group discussion was the proposed generic list of essential data elements for active PV

which would be applicable to active TB disease (Table 1.a) and not specific for any new drug or

regimen cohorts. The minimum dataset (i.e. "essential" data) are highlighted in bold and other data

elements that are in regular font would not be essentially required, but countries/settings may want

to collect as additional data to the minimum essential dataset. In addition to this list of data

elements, a data dictionary with detailed description of each variable and instructions for electronic

database setup will be developed based on the discussion at the working group.

WG2.Analysis,sharingandcommunicationofCEMdata

This group was led by KNCV, WHO and the participants from Belarus. It focused on the organization

of CEM, indicators, detection of signals, inference of causality, messaging and sharing of findings. By

the end of the sessions the group proposed that causality/relationship assessment would be the

primary responsibility of the national PV centre but also depended upon the treating physician

reporting suspected signals. Taking into account the very complicated clinical conditions and

overlapping toxicity of anti‐tuberculosis multi‐drug therapy in patients with M/XDR‐TB, it is

important to perform causality assessment with the involvement of treating physicians or clinical

experts who have clinical experience of M/XDR‐TB treatment. Establishment of the expert

committee with the involvement of PV and TB clinical experts for assessment/re‐assessment of

causal relationship and identification of the suspected drug is a successful experience as illustrated

in Belarus. All events would need to be reported as a) this would allow for establishment of a full risk

profile including occurrence of common, non‐serious but severe reactions and b) this would limit the

missed or delayed detection of rare but important reactions. Reporting of the events on the

database of the PV centre was recommended. Regular analysis of events for every case based on the

AE report received at the National PV Centre and quarterly review of the data and intermediate

report were suggested as a good practice. The way that this was done differed by countries: for

instance in Morocco a line‐listing of events was visually checked while in Belarus summary indicators

were used to record the number of patients enrolled, lost to follow‐up and who have adverse events.

Adverse events are stratified by seriousness and severity. It was noted that with respect to signals

the CIOMS and WHO definitions differ. Five summary indicators were drafted, of which two were

considered essential and proposed to be “mainstreamed” into PMDT care (Table 2). On the basis of

these and subsequent discussions, an outline for a “drug‐safety profile” was proposed (Table 3).

WG3.ResponsibilitiesofdifferentstakeholdersinPVsupport

In order to successfully introduce active PV, a clear idea of the roles and responsibilities of the key

active players is necessary. There are 4 main actors in implementing active PV:

1. National TB Program (from central to clinic level); 2. PV centre (or its proxy in countries where there is no PV centre); 3. Technical partners; and 4. Donors

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The WG noted that there are some overlapping areas, and all groups should feedback into one

another. Whenever possible, existing committees and groups will be used and the goal is to avoid

setting up a specialized system for TB if a system already exists. Several overarching themes and

general responsibilities came up. It was felt that all stakeholders should be responsible for

communication, integration, consultation, and advocacy. In addition, it is clear that the exact roles

and responsibilities may vary from country to country, and that countries will need to adapt the

generalities of this plan to their specific situations. Finally, many decisions about who should take on

which roles will depend on both politics and finances and it may be determined how these will shape

the exact nature of the roles prior to implementation.

Finally, although these are the 4 main players in the establishment of PV, the Ministry of Health

must oversee all work and give the mandate for active PV for DR‐TB. PV and TB services may be

located in different branches or arms of the Ministry, and it may be complicated for full

collaboration to occur without such a mandate.

1) NTP (there is usually 1 NTP in the country and in this document refers to the entire NTP from the central to the peripheral level)

Initiating discussion on the need for PV for TB and DR‐TB;

Educating PV centre on TB, DR‐TB, its management, its AEs, and the drugs used to treat it;

Collecting and managing data;

Mobilizing funding;

Training their NTP staff and managers;

Establishing the PV committee and team;

Outlining the incentive plan (if any) for providers;

Developing budget and HR needs for the NTP

Ongoing data collection plus monitoring and supervision.

2) PV Centre (there is usually 1 PV centre in the country; if no PV centre exists, a proxy can be nominated until one exists, usually this will be the National Regulatory Authority or a national PV committee under the guidance of the National Regulatory Authority and/or NTP)

Providing feedback on AEs and medications to the community so that they can see why PV is

important;

Analysing and reporting on data, including signal generation, formal reports to other groups

(i.e. supranational centres, WHO, etc.);

Performing causality assessment;

Communicating with the larger community (i.e. the media);

Training PV and NTP staff;

Establishing the PV committee and team;

Supervising and monitoring implementation of PV;

Developing budget and HR needs for the PV centre and NTP.

3) Technical Partners (there may be many of them, and they could include some non‐traditional partners, including contract research organizations, academic institutions and universities, and families and communities)

Performing independent assessments;

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Catalysing and brokering conversations and meetings;

Training in the short‐term;

Providing long term TA to support the PV centre and the NTP

Providing TA for funding applications

Compiling a list of TA providers and resources

Assisting in developing international/national policy on PV and supporting its implementation

4) Donors (there are usually many, and some overlap with the technical partners; should also consider PV‐specific streams of funding, the role of drug companies, etc.)

Advertising grants appropriate for PV and Health Systems Strengthening;

Ensuring supplies are available to treat and evaluate AEs, not just report them;

Ensuring PV centres and NTPs take responsibility for their roles

Focusing on sustainability

Integrating streams of funding

Simplifying and harmonizing reporting indicators for different funders and reports

Nextsteps for the jointplan for thecollectionandanalysisofsafetydataThe revised parameters for collection and analysis of data, as well as the roles and responsibilities

for active PV among different stakeholders, as at the end of the working group discussions were

circulated to all the participants in the meeting (Tables 1‐4). Once the consultation and feedback on

these parameters are finalised, the specifications will be integrated into the second edition of the

“Companion handbook to the WHO guidelines for the programmatic management of drug‐resistant

tuberculosis scheduled for publication in late 2014” under the section dealing with PV.

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Tables

Table1:DatacollectionforactivepharmacovigilanceinTBpatients

Table1.a.Essentialdataelementsforcohorteventmonitoring(CEM)

Note:

This list defines data elements which are essential for CEM. Many of these variables are generally collected for the monitoring of TB patients on MDR‐TB treatment. 1

The essential laboratory tests which need to be conducted will be determined by the study or programme protocol. A schedule for the screening for adverse events and for laboratory, clinical and radiological testing is also recommended to be developed (see Tables 1.b. and 1.c. for examples relating to a bedaquiline‐based regimen and a shorter MDR‐TB regimen). As a minimum, the laboratory test results need to be entered into the PV database whenever the values are abnormal (mild, moderate or severe grades as per the reference text used) under “AE Type” field; see additional footnotes beneath the table below). Both the list of data elements and the frequency of testing are expected to be validated and customized based on local needs before they are integrated in the CEM protocol of the programme.

Electronic methods will be indispensable for the collection and management of these data.

1 Companion handbook to the WHO guidelines for the programmatic management of drug‐resistant tuberculosis.

(WHO/HTM/TB/2014.11) [Internet]. Geneva, World Health Organization. 2014. Available from: apps.who.int/iris/bitstream/10665/130918/1/9789241548809_eng.pdf.

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A. Data collected at single time point (at start of treatment with drug/regimen of interest)

Data element Categories or values (when applicable)

Facility information

Country Country lookup list

Facility name and address free text

Reporter free text

Scale used for grading of severity of AEs*WHO scale; CTCAE grading system; DAIDS AE Grading Table; Other

Patient information

Patient ID free text

Patient name free text

Date of birth DD‐MMM‐YYYY

Sex M; F

Height ###.#

Height Unit cm; IN

Weight** ###.#

Weight Unit** kg; LB

Weight Date** DD‐MMM‐YYYY

Pregnancy Status** Y; N; U; NA

Pregnancy Status recording date** DD‐MMM‐YYYY

If pregnant, gestation week** ##

Breastfeeding mother Y; N; U; NA

Cavities on baseline chest x‐ray Y; N; U

Site of TB PTB only; PTB+EPTB; EPTB only; Unknown

Extrapulmonary TB site

Pleural; Lymphatic, intrathoracic; Lymphatic, extrathoracic; Genito‐urinary; Osteo‐articular; Disseminated; Peritoneal & Digestive; Central nervous system; Other

Previous TB treatment? Y; N; U

Injecting Drug Use Within Past Year Y; N; U

Excessive alcohol use within the past year

Y; N; U

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Tobacco use within the past year Y; N; U

Any concomitant diagnoses or events*** free text

Documented HIV infection Y; N; U

AFB smear result Positive, Negative, Unknown

Isoniazid susceptibility by any laboratory test(s) result(s) (baseline)

SUSCEPTIBLE; RESISTANT; INDETERMINATE; UNKNOWN

Rifampicin susceptibility by any laboratory test(s) result(s) (baseline)


Kanamycin susceptibility by any laboratory test(s) result(s) (baseline)


Amikacin susceptibility by any laboratory test(s) result(s) (baseline)


Capreomycin susceptibility by any laboratory test(s) result(s) (baseline)


Ciprofloxacin susceptibility by any laboratory test(s) result(s) (baseline)


Ofloxacin susceptibility by any laboratory test(s) result(s) (baseline)


Levofloxacin susceptibility by any laboratory test(s) result(s) (baseline)


Moxifloxacin susceptibility by any laboratory test(s) result(s) (baseline)


*WHO scale (http://www.who.int/medicines/publications/Pharmaco_TB_web_v3.pdf); Common Terminology Criteria for Adverse Events (CTCAE) grading system (http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010‐06‐14_QuickReference_5x7.pdf); Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (“DAIDS AE Grading Table”) (http://www.niaid.nih.gov/LabsAndResources/resources/DAIDSClinRsrch/Documents/daidsaegradingtable.pdf).

**Variables collected both at the baseline and repeatedly.

***List all current and past medical conditions; include the onset date and either record the date of recovery or, if the condition is ongoing, note that it ‘continues’ (Record approximate date if exact date is unknown).

B. Data collected at single time point (at end of treatment with drug/regimen of interest)


Outcome at end of current treatment episode

Cured; Treatment completed; Treatment failed; Died; Lost to follow‐up; Not evaluated

End‐of‐treatment outcome Date DD‐MMM‐YYYY

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C. Repeatedly collected data


Adverse Events (AEs) including new events or changes in pre‐existing conditions


AE type* free text

AE MedDRA/WHO‐ART numeric code** free text

Onset date DD‐MMM‐YYYY

Maximum severity grade of event by the time of this report as per the scale used in the programme

Is the adverse event serious? Y; N; UNKNOWN

If "yes", indicate type of SAE A congenital anomaly or birth defect Y; N

Persistent or significant disability or incapacity Y; N

Death Y; N

Initial or prolonged hospitalization Y; N

Life Threatening Y; N

A medically important event Y; N

Clinician action taken with regard to TB drug suspected causing AE

Dose not changed; Dose reduced; Drug interrupted; Drug withdrawn; Not applicable

Was the AE attributed to one or more anti‐tuberculosis drugs? **

Y; N; UNKNOWN

Select the first most likely drug that the AE may be attributed to **

Anti‐TB drug abbreviation from the list [Name]

Select the second most likely drug that the AE may be attributed to **


Select the third most likely drug that the AE may be attributed to **


Outcome (Status of the AE) Resolved; Resolved with sequelae; Fatal; Resolving; Not resolved; Unknown

If resolved, provide resolution date DD‐MMM‐YYYY

Tuberculosis Treatment


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Drug name Anti‐TB drug abbreviation from the list [Name]

Daily Dose ####

Unit of dose mg

Days/week #

TB drug start date DD‐MMM‐YYYY

TB drug end date DD‐MMM‐YYYY

Concomitant Medications


Concomitant Drug Name free text; use substance name as per PV reporting if possible

Concomitant drug start date DD‐MMM‐YYYY

Concomitant drug stop date DD‐MMM‐YYYY

Patient weight

Weight ###.#

Weight Date DD‐MMM‐YYYY

Weight Unit kg; LB

Pregnancy status

Pregnancy Status Y; N; U; NA

Pregnancy Status recording date DD‐MMM‐YYYY

If pregnant, gestation week ##

*If the AE is due to an abnormal laboratory test result, indicate the AE type (e.g., “anaemia”) and enter the value of the test result with units (e.g. “Hemoglobin 4.9 mmol/L”).

**Done by national PV committee or at PV Centre.

17

Anti‐TB drug abbreviation list

Name Abbreviation

Amikacin AMK

Amoxicillin‐clavulanate AMOX‐CLAV

Bedaquiline BDQ

Ciprofloxacin CFX

Clofazimine CFZ

Capreomycin CM

Cycloserine CS

Delamanid DLM

Ethambutol E

Ethionamide ETO

Gatifloxacin GFX

Gemifloxacin GEM

Imipenem‐Cilastatin IPM

Isoniazid H

Kanamycin KM

Levofloxacin LFX

Linezolid LZD

Meropenem MPN

Moxifloxacin MFX

Ofloxacin OFX

P‐aminosalicylic acid PAS

Pretomanid PA

Protionamide PTO

Pyrazinamide Z

Rifabutin RBT

Rifampicin R

Rifapentine RPT

Streptomycin S

Sutezolid SUT

Thioacetazone T

Terizidone TRD

18

Table1.b.ScheduleofroutinetestsinadditiontostandardPMDTassessmentsforbedaquiline‐basedregimentreatmentmonitoring

Laboratory Evaluation

Baseline Week 2 Monthly for first 6 months

Quarterly for remainder of therapy

Symptom directed

Liver function tests

X X X Nausea, vomiting, jaundice, abdominal pain

Lipase X* Nausea, vomiting, jaundice, abdominal pain

Potassium X X X QTc prolongation, cramps, palpitation

Magnesium X* QTc prolongation, cramps, palpitation

Calcium X* QTc prolongation, cramps, palpitation

Albumin X+ X

CBC X X X Fatigue, nose bleeds, gum bleeds, easy bruising

12‐lead ECG (for follow up, digital measures of QTc can be done instead of full 12‐lead ECG)

X X X# X# Dizziness, syncope, palpitations

*If available. + If needs DEL. # at a minimum ECGs should be checked at week two then quarterly, but some programs check them on a monthly basis.

19

Table1.c.Scheduleofexaminationsduringintensive,continuation,andfollowupphasesfor9‐monthtreatmentregimen*(EXAMPLEfromanexistingprotocol)

Intensive phase, 4 months (can be extended by 1 or 2 months)

Continuation phase, 5 months Follow up phase, 12 months after end of treatment

Examination M0 M1 M2 M3 M47 M5 M6 M7 M8 M9 6M 12M

Written Informed Consent X

Clinical evaluation X X X X X X X X X X X X

Sputum smear X X X X X XX X X X X XX X X

Sputum culture X10 X X X X X X X X X X X

DST1 X X X

X8 X

8

Xpert MTB/RIF X X X

LPA (GenoType MTBDRsl® assay) X X9 X

9

Audiometry2 X X X

Simple hearing test4 X X X X X

Chest X‐ray X X X X

Complete Blood Count3 X X X

Serum creatinine4 X X X X X

Serum potassium4 X X X X X

Blood glucose X

Thyroid tests: TSH X X

Liver function tests5 X X X X X X

ECG6 XX X X X X

Pregnancy test (for women) X

HIV test X

If HIV‐positive, CD4 count X

Hepatitis B (HepBs Antigen) and hepatitis C (HCV antibodies)

X

Visual acuity X

20

Notes for table 1.c:

*4 Km(Cm) Cfz Mfx(Lfx) E H Z Pto / 5 Cfz Mfx(Lfx) E Z

1. If culture‐positive. DST will be done for H, R, Km, Cm, Ofx.

2. If injectable drug is given for more than 4 months, examinations should be continued every 2 months until injections are stopped

3. RBC count, WBC count, hemoglobin, hematocrit, WBC differential count, platelet count

4. If injectable drug is given for >4 months, continue monthly examination of tests that should be done on the 4th month of treatment

till injections are stopped

5. Bilirubin, SGOT, SGPT, alkaline phosphatase, gGT

6. ECG should be obtained at the baseline and repeated at least 2, 12, 24 and 36 weeks after starting treatment. ECG should be repeated as necessary in case of clinical suspicion of heart rhythm and conduction disturbances.

7. If the intensive phase is extended by 1 or 2 months, the Month 4 examinations should be repeated in each additional month.

8. If culture‐positive, DST for H, R, Km, Cm, Ofx, and genotyping of positive follow up isolate as well as stored baseline isolate from this patient would be performed.

9. If smear‐positive or Xpert‐positive.

10. Initial M. tuberculosis isolate stored at ‐80°C.

21

Table2:ProposedminimumprogrammaticindicatorsforpharmacovigilanceforTB

Class Importance Indicator number and name

Calculation Stratification Expressed as

Data sources Level Period of assessment

Notes

Coverage (process)

Essential 1) Target RR‐/MDR‐TB patients included in cohort event monitoring

Numerator: Number of TB cases started on target treatment included in CEM during the period of assessment.

Denominator: Number of TB cases started on target treatment during the period of assessment and who were eligible for CEM.

None Absolute numbers, proportion

Numerator: CEM register. Denominator: Second‐line TB treatment register

National; PV centre

3 months To be computed during the period of recruitment but not in the post‐treatment observation phase

Completeness (process)

Optional 2) RR‐/MDR‐TB patients retained in the cohort for event monitoring

Numerator: Number of TB cases completing CEM by the period of assessment.

Denominator: Total number of TB cases included in CEM at the start of their treatment.

Reason for stopping

Absolute numbers, proportion

Numerator: CEM register. Denominator: CEM register.

National; PV centre

12 months To be computed during the period of patient recruitment and during the post‐treatment observation phase

Stratify by reason for stopping (e.g. success, died, treatment failed, loss to follow up, and exclusion criterion developing after start of treatment such as pregnancy).

22




Notes

Serious adverse events

Essential (but stratification optional)

3) RR‐/MDR‐TB patients included in CEM with any serious adverse event

Numerator: Number of TB cases included in CEM during the period of assessment with one or more serious adverse events.

Denominator: Number of TB cases included in CEM during the period of assessment.

By organ group; by outcome



National;

PV centre

3 months To be computed during the period of patient recruitment and during the post‐treatment observation phase

Indicate outcome (deaths, hospitalisations, disability)

Adverse reactions associated with target treatment

Optional 4) Frequency of ADRs associated with the target treatment

Numerator: Number of ADRs attributed to target treatment among patients on CEM.

Denominator: Number of TB cases included in CEM during the period of assessment.

By organ group; by seriousness/severity



National;

PV centre

3 months To be computed during the period of patient recruitment and during the post‐treatment observation phase.

Only to be reported after causality assessment (e.g. de‐challenge, re‐challenge) suggests the target treatment as the causative agent (certain, probable or possible).

The same patient may have several ADRs (therefore the unit of measurement is the ADR and not the patients).

23




Notes

Adverse reactions associated with target treatment

Optional 5) Time to development of ADRs associated with the target treatment

The difference in days between the date of start of the target treatment and the date of the first detected onset of the ADR attributed to it

By organ group

Number of ADRs included in the calculation; median interval and interquartile range in days


CEM centre

6 months To be computed during the period of patient recruitment and during the post‐treatment observation phase. The calculation is done for each reaction attributed to the target treatment; the same patient may have several ADRs computed (the unit of measurement is the ADR and not the patients); if a particular ADR recurs in the same patient during the CEM it is not calculated again. Only to be reported after causality assessment (e.g. de‐challenge, re‐challenge) suggests the target treatment as the causative agent (certain, probable or possible).

24

Table3:Elementsforasummaryprofileofdrugsafety/toxicity

Draft framework for the harmonized and standardized summarization of both added benefit and risk

associated with an intervention

Dimension Additional notes on data sources, methodology etc.

The benefit : toxicity profile of

the baseline MDR‐TB regimen

The MDR‐TB regimen which constitutes the most widely used standard of

care is described in terms of its effectiveness and associated harms; this

dimension of the profile uses information originating from the published

literature; trials (un‐/published); observational studies and cohorts

(including nested case‐controls); prospective CEM data and also other PV

data from spontaneous reporting

Safety concerns associated

with a specific drug or regimen

The characteristics (organ class), risk, severity, drug‐drug interactions

(DDI) and other safety concerns are summarized from the literature as

well as local data (including CEM). The known concerns are described,

such as increased mortality or prolonged QTc in Bdq users; suspected

reasons for lack of efficacy such as resistance, drug quality issues

Quantifying risk & benefit As much as possible the safety concerns are also expressed in terms of

risk, such as per 100 or 1000 exposures; as relative risks. The

effectiveness is generally expressed in terms of % successful outcome or

cure

Risk factors These include host‐related predispositions to harms, such as

comorbidities, severity of TB disease, DDI, subpopulations (age‐

group/sex). These could form the basis of contraindications or caution in

use of the regimen or drug

Signal detection The procedure followed for relationship and causality assessments and

detection of signals in the cohort is described and any departures from

agreed methodologies described. Signal detection is attempted both at

country‐ and supranational level. Any preliminary signals are discussed

with the regulators and manufacturer before wide communication

Preventive measures Advice on avoidance of harm/toxicity, precautions, contraindications

25

Table4:RolesandresponsibilitiesofpartnersforcohorteventmonitoringforTB

The agency responsible for lead responsibilities may differ depending on the country circumstances

Active PV component (CEM) Lead responsibility

Establishment of CEM committee & secretariat National PV centre (NPV, if available)

Management and supervision ‐ At start: National PV centre

‐ At “maintenance” stage: TB programme

Preparation of CEM protocol, including plan for

data analysis and communication

National PV centre

Design and production of forms for data

collection

National PV centre

Submission for ethical approval* National PV centre

Staff training National PV centre (in collaboration with NTP)

Collection of data TB programme**

Electronic database for MDR‐TB patients on

treatment, for consolidation of PV data

‐ If none exist: National PV centre

‐ If PMDT database exists : TB programme

Relationship/causality assessment and signal

identification

National PV centre

* as required by local rules and standards for public health surveillance

** In cases where the private sector is also involved in active pharmacovigilance, the national TB control programme needs to maintain an effective liaison with these providers to ensure that there is consistent and comprehensive monitoring of drug safety. Likewise, when TB care is provided in general hospitals and specialist centres outside of the usual span of control of the national TB control programme, then a good rapport is needed to ensure that the required activities are conducted to good effect. For the coding of adverse events it is suggested that the TB doctor records the event in free text form and then this is coded into the exact term by an expert in pharmacovigilance at the NPV Centre.

26

Acknowledgement

The “Inter‐regional workshop on pharmacovigilance for new drugs and novel regimens for the

treatment of drug‐resistant tuberculosis” was organised jointly by WHO/HQ (Essential Medicines

and Pharmaceutical Policies (EMP), the Global TB Programme (GTB)), the Regional Office for the

Western Pacific of WHO (WPRO), and the WHO Representative Office in Viet Nam with the support

of USAID and UNITAID.

References

1. A practical handbook on the pharmacovigilance of medicines used in the treatment of tuberculosis: enhancing the safety of the TB patient. Geneva, WHO, 2012.

2. Companion handbook to the WHO guidelines for the programmatic management of drug‐resistant tuberculosis. (WHO/HTM/TB/2014.11). Geneva, World Health Organization. 2014. Available from: apps.who.int/iris/bitstream/10665/130918/1/9789241548809_eng.pdf

3. The use of bedaquiline in the treatment of multidrug‐resistant tuberculosis. Interim policy guidance (WHO/HTM/TB/2013.6). Geneva, World Health Organization. 2013

4. The use of delamanid in the treatment of multidrug‐resistant tuberculosis. Interim policy guidance (WHO/HTM/TB/2014.23). Geneva, World Health Organization. 2014

5. Policy Implementation Package for new TB drug introduction (WHO/HTM/TB/2014.22). Geneva, World Health Organization. 2014

6. The use of short regimens for treatment of multidrug‐resistant tuberculosis (www.who.int/tb/challenges/mdr/short_regimen_use/)

7. Research Protocol ‐ Effectiveness of a simplified short regimen for Multidrug Resistant Tuberculosis treatment in Karakalpakstan, Uzbekistan ‐ MSF Field Research. (fieldresearch.msf.org/msf/handle/10144/322296)

8. Briefing package. Division of Anti‐Infective Products Office of Antimicrobial Products CDER, FDA. SirturoTM (bedaquiline 100 mg tablets) For the treatment of adults (≥ 18 years) as part of combination therapy of pulmonary multi‐drug resistant tuberculosis (MDRTB). Applicant: Janssen Research and Development, L.L.C FDA Anti‐Infective Drugs Advisory Committee Meeting Silver Spring, MD. Date: November 28, 2012. (www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti‐InfectiveDrugsAdvisoryCommittee/UCM329258.pdf)

9. European Medicines Agency ‐ Human medicines ‐ Deltyba. (www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002552/smops/Positive/human_smop_000572.jsp&mid=WC0b01ac058001d127&source=homeMedSearch&category=human)

10. Global tuberculosis report 2014. Geneva, World Health Organization, 2014 (WHO/HTM/TB/2014.08)

11. WHO Multidrug‐resistant tuberculosis (MDR‐TB) website (www.who.int/tb/challenges/mdr)

12. Definitions and reporting framework for tuberculosis – 2013 revision. Geneva, World Health Organization, 2013 (WHO/HTM/TB/2013.2)

27

13. Electronic recording and reporting for tuberculosis care and control. Geneva, World Health Organization, 2012 (WHO/HTM/TB/2012.22)

14. Guidance on ethics of tuberculosis prevention, care and control. Geneva, World Health Organization, 2010 (WHO/HTM/TB/2010.16)

15. WHO Guidelines for the programmatic management of drug‐resistant tuberculosis, 2011 update. Geneva, World Health Organization, 2011 (WHO/HTM/TB/2011.6)

16. MDR‐TB planning toolkit (www.path.org/publications/files/TB_mdr‐tb_toolkit.pdf)

17. Expecting the worst. Anticipating, preventing and managing medicinal product and other health care crises. 2nd ed. Uppsala, Sweden; 2010

28

Annex1:Agendaofthemeeting

Inter‐regional workshop on pharmacovigilance for new drugs and

novel regimens for the treatment of drug‐resistant TB

12‐14 November 2014

Day 1: Wednesday, 12 November 2014

Chair : WPRO

09:00 – 09:20 Opening: Message from host country MOH Viet Nam

09:20 – 09:30 Practical information and introduction of participants Chair

09:30 – 09:40 Objectives of the workshop and key documents WHO

09:40 – 10:10 MDR‐TB : global response and WHO policies E. Jaramillo

10:10 – 10:25 Break

10:25 – 10:50 Active pharmacovigilance : rationale & methods S. Setkina

10:50 – 11:10 Principles of cohort event monitoring (CEM) C. Suku

11:10 – 11:35 Safety monitoring in TB & HIV patients in Belarus S. Setkina/A.

Skrahina

11:35 – 12:00 Safety monitoring in TB & MDR‐TB patients in Viet Nam H. Anh/H. Thuy

12:00 – 12:20 Safety monitoring for shorter regimens in Bangladesh

and Niger

A. Piubello

12:20 – 13:00 Discussion on

‐ common challenges in PV for MDR‐TB patients

‐ new drugs and novel regimens

‐ roles and responsibilities of different partners

All

13:00 – 14:00 Lunch

14:00 – 14:30 Principles of causality assessment R. Benkirane

14:30 – 15:00 Data collection and analysis for CEM of MDR‐TB patients S. Setkina/A.

Skrahina

15:00 – 15:15 Discussion All

15:15 – 15:30 Introduction to Group Work WHO

29

15:30 – 16:00 Break

16:00 – 17:30 Session 1 – Main questions, discussion

WG1. Collection and management of CEM data

WG2. Analysis, sharing and communication of CEM data

WG3. Responsibilities of different stakeholders in PV

support

Leads

US CDC/MSH

KNCV/Belarus

WHO/USAID

Day 2: Thursday, 13 November 2014

Chair : US CDC

09:00 – 10:30 Session 2 – Discussions

WG1. Collection and management of CEM data

WG2. Analysis, sharing and communication of CEM data


support

Leads

US CDC/MSH

KNCV/Belarus

WHO/USAID

10:30 – 10:45 Break

10:45 – 13:00 Session 3 – Joint discussion & preparation of conclusions

WG1 & WG2. Joint discussion on the methods proposed

for (i) the collection and management of CEM data and

(ii) the analysis, sharing and communication of CEM data


support

Leads

US CDC/MSH &

KNCV/Belarus

WHO/USAID

13:00 – 14:00 Lunch

14:00 – 14:30 Collection and management of CEM data WG1

14:30 – 15:00 Analysis, sharing and communication of CEM data WG2

15:00 – 15:30 Responsibilities of different stakeholders in PV support WG3

15:30 – 16:00 Break

16:00 – 17:30 Discussion on the three main work‐streams and way

forward

All

(18:00 – 19:00 Closed meeting of WG Leads)

30

Day 3: Friday, 14 November 2014

Chair : Médecins sans Frontières

09:00 – 09:45 “Expecting the worst”

Anticipating, preventing and managing medicinal product

crises

B. Hugman

09:45 – 10:15 Ethical issues when monitoring of safety and

effectiveness of MDR‐TB patients – case studies

E. Jaramillo

10:15 – 10:30 Break

10:30 – 11:00 Proposed structure & content for the joint plan for the

collection and analysis of safety data for new drugs and

shorter regimens

WHO

11:00 – 12:30 Discussion on (among others)

‐ detecting signals

‐ causality assessment

‐ routes of reporting safety data (national,

supranational)

‐ integrating PV indicators in the monitoring

framework for RR‐/MDR‐TB

‐ public communication of serious ADRs

All

12:30 – 12:45 Conclusion, next steps and finalisation of plan by end

2014

WHO

12:45 – 13:00 Closing MOH Viet Nam &

WHO

31

Annex2:Listofparticipants

Name Title/Contact address

Bangladesh

Mirza Nizam Uddin

Deputy Programme Manager and Focal Point of MDR‐TB, National Tuberculosis Control Programme Directorate General of Health Services

Salim Barami Director. Directorate General of Drugs Administration

Belarus

Alena Skrahina

Deputy Director, Scientific Director Republican Scientific & Practical Center for Pulmonology & Tuberculosis

Sviatlana Setkina

Specialist for pharmacovigilance, Centre for Examinations and Tests in Health Care, Ministry of Health

Indonesia

Rudy Hutagalung

Focal Point of PMDT, National Tuberculosis Programme. Directorate General of Disease Control and Environmental Health. Ministry of Health

Endang Lukitosari

Focal Point of TB Drug Logistic, National Tuberculosis Programme. Directorate General of Disease Control and Environmental Health. Ministry of Health

Kazakhstan

Gulnaz Mussabekova

Head of Monitoring and Assessment Group, National Center for Tuberculosis

Sagit Bektassov

Chief, Department for Treatment of MDR and XDR‐TB Patients National Center for Tuberculosis

Laos

Khamla Choumlivong

Deputy Director, Settathirath Hospital Ministry of Health

Soulyvanh Keokinnal

Deputy Chief, Public Health Pharmacy Management Division. Food and Drug Department, Ministry of Health

Myanmar

Cho Cho San

Assistant Director (TB). Department of Health Ministry of Health

Tin Wah Wah Win

Deputy Director (Drug Control) Department of Food and Drug Administration

32

Philippines

Lanette Lee A. Querubin

Food‐Drug Regulation Officer, Pharmacovigilance Unit Center for Drug Regulation and Research Food and Drug Administration

Vivian Lofranco Medical Specialist, Lung Center of the Philippines

Vietnam

Nguyen Viet Nhung

Director, National Lung Hospital Manager, National TB Programme

Hoang Thi Thanh Thuy Head of PMDT Group. National TB Programme

Nguyen Hoang Anh

Director, National Centre of Drug Information and Adverse Drug Reactions Monitoring

Hoang Thanh Mai

Vice Head, Drug information and Advertising Management Division, Drug Administration of Viet Nam Ministry of Health

Damien Foundation

Alberto Piubello Representative, Damien Foundation Niger Medical advisor to NTP. Niamey ‐ Niger

Souleymane Mahmadou Bassirou

Damien Foundation NigerNiamey ‐ Niger

Centers for Diseases Control and Prevention (US CDC)

Ekaterina Kurbatova Senior Service Fellow MDR‐Team, International Research and Programs Branch Division of TB Elimination. Atlanta, Georgia, USA

Joseph Cavanaugh Medical Officer. Division of TB Elimination. Atlanta, Georgia, USA

Global Fund to fight AIDS, Tuberculosis and Malaria

Yamil Cabrera TB Disease Advisor Geneva, Switzerland

Interactive Research and Development (IRD)

Saira Nadia Khowaja Director, Development ProfessionalSingapore

KNCV Tuberculosis Foundation

Edine W. Tiemersma Senior Epidemiologist. The Hague, The Netherlands

Susan van den Hof Senior Epidemiologist. The Hague, The Netherlands

Tiar Salman Senior Technical Officer. Drug Management and Logistic Jakarta, Indonesia

Management Sciences for Health (MSH)

Ruth Lopert Deputy Director, Pharmaceutical Policy & Strategy Center for Pharmaceutical Management, MSH. Arlington, VA, USA

33

Médecins Sans Frontières (MSF)

Miguel Serrano Section Pharmacist, Operational Centre Amsterdam, Amsterdam, The Netherlands

The International Union Against Tuberculosis and Lung Disease (IUATLD)

Arnaud Trébucq Tuberculosis Division Manager, IUATLD. Paris, France

USAID

Alexander Golubkov Senior TB Technical Advisor, USAID TB Team. Washington DC, USA

Thomas Chiang Sr. TB Technical Advisor, Focal Person TB Drugs USAID TB Team. Washington DC, USA

WHO Collaboration Centres on Pharmacovigilance

Raja Benkirane Moroccan Pharmacovigilance Centre. Rabat, Morocco

Bruce Hugman Communication Consultant, Uppsala Monitoring Centre (UMC), Uppsala, Sweden. (Based in Thailand)

WHO Consultant/Technical Advisor

Jennifer Furin Assistant Processor of medicine, WHO Consultant CWRU, USA

Comfort Kunak Suku National Pharmacovigilance Centre.National Agency For Food And Drug Administration And Control. Abuja, Nigeria

Mamel I. Quelapio Consultant on programmatic management of drug‐resistant TB. Cavite, Philippines

WHO Headquarters ‐ Geneva, Switzerland

Christian Lienhardt Scientist. GTB/PSI ‐ Policy, Strategy and Innovations (HQ/HTM/GTB/PSI)

Dennis Falzon Scientist. GTB/LDR – Laboratories, Diagnostics and Drug‐Resistance (HQ/HTM/GTB/LDR)

Diana Weil Coordinator. GTB/PSI ‐ Policy, Strategy and Innovations (HQ/HTM/GTB/PSI)

Ernesto Jaramillo Medical Officer. GTB/LDR – Laboratories, Diagnostics and Drug‐Resistance (HQ/HTM/GTB/LDR)

Nguyen Nhat Linh Technical Officer. GTB/LDR – Laboratories, Diagnostics and Drug‐Resistance (HQ/HTM/GTB/LDR)

Shanthi Narayan Pal Technical Officer. Safety and Vigilance(HQ/HIS/EMP/RHT/SAV)

Leticia Megias Lastra Safety and Vigilance (HQ/HIS/EMP/RHT/SAV)

34

WHO Regional and Country Offices (PHL, VTN, LAO)

Tauhidul Islam Technical Officer. WPRO, Philippines

Woo‐jin Lew Medical Officer. Country office, Philippines

Jacques Sebert Consultant. Country office, Lao PDR

Katsunori Osuga Medical Officer. Country office Viet Nam

Pham Huyen Khanh National Professional Officer. Country office Viet Nam

Socorro Escalante Technical Officer. Country office, Viet Nam

OBSERVERS

Nguyen Thu Thuy Pharmacist, National TB Programme. Hanoi, Viet Nam

Vu Dinh Hoa The National Centre of Drug Information and Adverse Drug Reactions Monitoring. Hanoi, Vietnam

Nguyen Thien Huong

Representative of KNCV Tuberculosis Foundation in Viet Nam. Hanoi, Viet Nam

Pham Huy Minh USAID. Hanoi, Viet Nam

Vu Cao Cuong Deputy Director, Hanoi Lung HospitalHanoi, Viet Nam

Tran Ngoc Buu Deputy Director, Pham Ngoc Thach Hospital HCMC, Viet Nam

Phan Thuong Dat MDR‐TB Dept. Head, Pham Ngoc Thach Hospital HCMC, Viet Nam

Nguyen Hoang Giang The Union TB Technical Advisor Hanoi, Viet Nam

Agnes Gebhard KNCV Tuberculosis Foundation, The Hague, The Netherlands

Regina Osih

Clinical Advisor for TB‐HIVClinton Health Access Initiative. Hanoi, Viet Nam

Petchawan Pungrassami Bureau of Tuberculosis, Department of Disease Control Ministry of Health. Bangkok, Thailand

Usanee Ungcharoen Bureau Of Tuberculosis, Department of Disease Control Ministry of Public Health. Bangkok, Thailand