Update on DR−TB policies and - who.int Resource Development 1.1 HRD: What needs to be done 1.2 PMDT Centres of Excellence / Technical Assistance Centres ... Describes key elements

Update on DR−TB policies and guidance, and implications for

the National Strategic Plans

Divonne, France

17-26 February 2014

Background

• Globally, progress towards targets for universal access to diagnosis and treatment of MDR-TB is far off-track; in many countries this now constitutes a public health crisis.

• Almost 94 000 TB cases eligible for MDR-TB treatment (84 000 with MDR-TB and 10 000 with rifampicin resistance) were notified globally in 2012

• Just over 77 000 cases were reported to have been placed on MDR-TB treatment during the same period

• Patients reported to be on long waiting lists for treatment. • The global treatment success rate is under 50% due to high levels of

mortality and large numbers of patients being lost to follow-up. • At least one case of XDR-TB in 92 countries by the end of 2012

Countdown to 2015, Global Tuberculosis Report 2013, Supplement. WHO/HTM/TB/2013.13

Overall objective

• To ensure inclusion of activities and funding needs for sustaining current efforts and scale-up of Programmatic management of drug-resistant TB (PMDT)

– Key is to anticipate future needs taking into account updates on policies and recommendations

However the presentation does not intend to provide

in-depth technical details of the subject areas covered

Basic documents for guiding PMDT component of the NSP

2008

2011 NEW

in 2014

Overview 1. Human Resource Development

1.1 HRD: What needs to be done 1.2 PMDT Centres of Excellence / Technical Assistance Centres 1.3 Community−based and PPM activities

2. Treatment regimens 2.1 SLD regimens for MDR−TB 2.2 Shorter treatment regimens

3. Rational introduction of new TB drugs and regimens 3.1 WHO Strategic Plan

3.2 Introduction of bedaquiline 3.3 Compassionate use

4. Models of Care for MDR −TB 5. New definitions, reporting framework and electronic systems 6. Pharmacovigilance in TB care 7. Palliative care and Ethics 8. Infection control

1. Human Resource Development (HRD)

1.1 HRD: What needs to be done

• Perform a situational analysis of HR available for NTP in general and MDR-TB specifically where highly trained staff is needed

• Develop an HRD plan that is harmonised with needs of PMDT expansion plan – including number of staff with specific skills required at the various levels, with job descriptions

• Conduct competency and skills development activities i.e. tailored trainings and workshops. Complemented with supervision and on the job training

• Estimate the funding requirement for the activities

Planning the development of human resources for health for implementation of the Stop TB Strategy - A handbook (WHO/HTM/TB/2009.407)

HRD: Activities that could be budgeted

• Consultancies/Workshops for: – Situational analysis

– Development of an HRD plan

– Training plans

• Conduct trainings: – Training of trainers

– National/sub-national training

– International workshop attendance

– International TA for facilitating training

• Performing the situational analyses: – Training

– Consultancy

1.2 PMDT Centres of Excellence (CoE) / Technical Assistance Centres (TAC) • Provide assistance to NTP for development of plans e.g NSP, PMDT

expansion etc, and implementation of these plans to the NTPs

• Support the training of in country-staff to improve the HR base for the expansion of MDR-TB treatment and management

• Support the NTP in translation and adoption of international guidelines and policy documents as and when required

• Support the NTP in monitoring PMDT expansion and provide critical inputs for overcoming the challenges

• Support NTPs in organising annual PMDT monitoring missions

• Support and conduct need based OR for PMDT expansion

• Liaise with in−country, international partners and other COEs for information exchange and international TA as and when required

CoE / TACs: Activities that could be budgeted

• Infrastructure upgrade

• Running costs of the centre

• Staff costs – training coordinator, specialists, support staff, etc

• International TA for establishing the COE

• Training curriculum and modules development

• Training costs (similar to HRD above)

• Supervision and monitoring support to the NTP

1.3 Community−based and PPM activities Involvement of the community and all health care providers can increase resources available to identify, diagnose and manage patients with MDR−TB

Community-based/ PPM activities for PMDT may include: • awareness-raising and community mobilization • referral for diagnosis of TB and MDR−TB, and facilitating access to

diagnostic services • treatment provision and observation, and adherence support • home-based palliative care for TB and related diseases

Budget items • Refer to budgeting tool

2. Treatment regimens

2.1 Composition of SLD regimens

• … a FQ should be used (strong recommendation/ very low quality evidence)

• … a later−generation FQ rather than an earlier−generation FQ should be used (conditional recommendation/very low quality evidence)

• … Eto (or Pto) should be used (strong recommendation/ very low quality evidence)

• … four second− line anti−TB drugs likely to be effective (incl. a parenteral agent), as well as Z, should be included in the intensive phase (conditional recommendation / very low quality evidence)

• … regimens should include at least Z, a FQ, a parenteral agent, Eto (or Pto), and either Cs or PAS if Cs cannot be used (conditional recommendation/very low quality evidence)

Duration of SLD treatment for M/XDR−TB

4.1 In the treatment of patients with MDR−TB, an IP of 8 months is suggested for most patients, and the duration may be modified according to the patient's response to therapy (conditional recommendation/very low quality evidence)

4.2 In the treatment of patients newly diagnosed with MDR−TB (i.e. not previously treated for MDR−TB), a total treatment duration of 20 months is suggested for most patients, and the duration may be modified according to the patient's response to therapy (conditional recommendation/very low quality evidence)

Budget items in SLD regimens for MDR−TB

• SLDs for the entire duration for each patient

• Monitoring and management of side effects including ancillary drugs

• Storage and management of drugs

• Psycho-social support

• Pharmacovigilance

2.2 Shorter regimens for MDR-TB Until sufficient evidence is available to inform a change in policy, WHO advises countries, on a case-by-case basis, to introduce shorter MDR-TB regimens if: 1. the project is approved by a national ethics review committee,

ahead of patient enrolment; 2. treatment is delivered under OR conditions following international

standards to assess the safety and effectiveness of these regimens; and

3. the PMDT and the research project are monitored by an independent monitoring board set up by, and reporting to, WHO

• Countries planning to use shorter regimens as per the criteria listed

above, will be offered TA to develop the required OR and programme management capacity if not yet available

• Support from WHO for such TA should be sought on a country-by-country basis prior to embarking on use of shorter MDR-TB regimens

http://www.who.int/tb/challenges/mdr/short_regimen_use/en/index.html

Budget items for shorter regimens

• Intended drugs to be used for the short regimen

• Pharmacovigilance

• All usual budget items for PMDT management, including diagnosis, treatment delivery, management of side effects, social support, etc

• Human resources and education material for ethics component (informed consent)

• Monitoring of the project

3. Rational introduction of new TB drugs and regimens

3.1 WHO Strategic Plan

Describes key elements of a process aimed at:

- producing policy recommendations for the treatment of TB (all forms), according to progress made in the development of new drugs or combinations of drugs;

and

- assisting countries in the implementation of these recommendations

http://www.who.int/tb/new_drugs/en/index.html

• Collect background information on TB epidemiology, health infra− structure, NTP structure & organization

• Capacity for diagnosis of TB & DRTB and treatment monitoring

• Drug resistance surveillance

• Safety monitoring: AEs/SAEs management; existence of a PV system

• Regulatory approval – NRA’s involvement

• Drug supply and management – incl. costs of drugs

• Selection of “Pilot sites" for initial deployment of new drugs with harmonised methods and surveillance

• Development of a protocol based on WHO guidance

• Related training/capacity building

• Establish/ensure partnerships (public and private sector)

• Community/patients’ representatives contribution

• Need for detailed budget plan taking these into account

Key elements for plan preparedness and budget items

3.2 Introduction of bedaquiline: Interim WHO policy guidance

Bdq may be added to a WHO-recommended regimen in adult patients with pulmonary MDR-TB (conditional recommendation, very low confidence in estimates of effect)

Subject to the following 5 conditions:

1. Treatment under close monitoring

2. Proper patient selection

3. Patient informed consent required

4. Treatment design based on WHO recommendations

5. Active pharmacovigilance in place

Budget items for introduction of bedaquiline

• Cost of "project" development, including TA, protocol development, oversight body, additional monitoring of patient and "project"

• The additional cost of Bdq ± other Group 5 drugs

• Human resource development and education material for ethics component (informed consent)

• Active pharmacovigilance

4.3 Compassionate use (CU)

Definition

• A physician usually requests directly to the manufacturer for a drug to treat a specific individual patient

• Manufacturer provides requested drug for free, and the patient’s condition must meet criteria established by the manufacturer, usually based on the absence of any other treatment with any likelihood of success

• Manufacturer provides guidelines on the use of the drug, but does not monitor use or outcomes

• Country where the patient will be treated must have regulations permitting such “compassionate use” of an unapproved drug

• The physician is responsible for following local regulations, such as importation or the need for Institutional Review Board approval

TA elements for CU

• Ensure that capacity to apply the basic international standards for patient treatment and care are in place

• Identify the existing national regulatory mechanisms for use of drugs in the pre-approval period

• Determine the criteria for a patient to be eligible to access drugs in the pre-approval period

• Define and apply the ethical standards that will protect patients, ensure equity and promote human rights

• Monitor the implementation of the programme

CU: Budget items

• Pharmacovigilance (see respective section)

• All usual budget items for drug procurement and management

• Human resources and education material for ethics component (written informed consent)

Recommendation Patients with MDR-TB should be treated using mainly ambulatory care rather than models of care based principally on hospitalization (conditional recommendation/ very low quality evidence)

4. WHO Policy on Models of MDR-TB Care

TA needs for models of care for MDR−TB

• Review of the existing policy to update it with most recent evidence, keeping in mind that

– “one size doesn’t fit all” and

– all NTPs will need to have hospital-bed capacity to manage MDR−TB patients for medical reasons (ranging from surgery to end-of-life care (see palliative care section) as needed

Budget items for models of care

• Consensus building workshop for national policy

• Costs associated with model of care as per budgeting tool and palliative care section – Costs of hospitalisation as per the model

– Patient travel costs – if facility based ambulatory care

– Social support

– Capacity building of staff/ community supporters

5. New definitions and reporting framework, electronic systems and MDR-TB Indicators

http://whqlibdoc.who.int/publications/2012/9789241564465_eng.pdf

www.who.int/iris/bitstream/10665/79199/1/9789241505345_eng.pdf

http://whqlibdoc.who.int/hq/2010/WHO_HTM_TB_2010.11_eng.pdf

Budget items

• Development of documents (policy, translation of the definitions, SOPs)

• Training of staff • Creation and maintenance of electronic systems • Infrastructure support (communications, electricity,

hardware, etc.)

6. Pharmacovigilance in TB care

www.who.int/medicines/publications/Pharmaco_TB_web_v3.pdf

“science and activities relating to the detection, assessment,

understanding and prevention of adverse effects or any other

drug-related problem.”

Pharmacovigilance in TB care

• Adverse drug reactions (ADRs) can lead to a TB patient interrupting treatment before completion

• It is important that ADRs, especially serious ones, be routinely monitored during the care of patients with drug-resistant TB and HIV/TB, especially with the advent of new drugs

Budget items for pharmacovigilance

• Refer to the budgeting tool

• The obligation not to abandon patients: especially “when curative treatment fails, there is an obligation to provide palliative and end-of-life care”

7. WHO perspective on palliative care

«Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness [like MDR-TB], through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psycho− social and spiritual»

http://www.who.int/cancer/palliative/definition/en/

WHO’s definition of palliative care

Budget items for palliative care

• Reinforcement of:

– Technical assistance

– The social support package to cover the psycho-social support

– Drugs to address respiratory distress and other symptoms

– Infection control items covering infrastructure to care for patients that are source of infection and for whom no treatment is available (XDR-TB treatment failures), which may include respiratory isolation rooms or shelters • Estimates to determine needs: XDR-TB is 10% of the MDR-TB burden;

treatment fails in 70% of XDR-TB patients; 50% of those in whom treatment fails die within the following 8 months, and the other 50% within 3 years after treatment failure is confirmed

TB care and control must be founded on sound ethics

• Patients need to be fully informed and counselled about TB and its treatment

• Health care providers have an obligation to support patients, and not to abandon them even treatment fails

• HCWs have a duty to care, but also rights to adequate protection

• Involuntary isolation is rarely justified and should always be seen as a very last resort

• Training on ethics of TB care is an item now of the WHO budgeting tool

8. Infection Control

Infection Control and prevention of MDR−TB

• There is urgent need to reinforce country TB infection control capacity when

– treatment fails in patients with M/XDR-TB

– diagnosis is made in the absence of treatment

– there is delay in treatment enrolment after diagnosis

– Treatment is interrupted for medical or operational reasons (drug stock out)

• Estimates for each item can be made to forecast need

Budget items for infection control

• Refer to the budgeting tool

Ensuring TA for PMDT

• The GF Standard Concept Note Instructions - Page 20

……Applicants must include in their funding request the relevant amount of funds for payment of the GLC fees for the technical assistance and advice they provide as indicated in the MoU between the Global Fund and WHO. Applicants who are one of the 27 countries with a high burden of MDR-TB and XDR-TB must include US$ 50,000 per year over the full term of the funding request. Non-high burden MDR-TB and XDR-TB countries must include US$ 25,000 per year.

THANK YOU

Acknowledgements: WHO-HQ LDR Unit and PSI Unit colleagues for their inputs and

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