Clinical Trials Clinical Trials in Low in Low

Resource Resource SettingsSettings

Ian MagrathIan Magrath

www.inctr.org

OutlineOutline

Propositions

Questions

Problems faced in developing countries

Addressing the Problems: Role of Clinical Trials

Infrastructure: knowledge transfer

Who pays?: sponsorships

INCTR Strategies Conclusions

Propositions -1Propositions -1

Interventions that are evidence-based are important everywhere;

Where resources are limited, wasted time, money and

expertise, or actual harm to people, have particularly significant socioeconomic

implications

Propositions - 2Propositions - 2

In spite of existing obstacles, the conduct of Phase II-IV clinical trials in

developing countries is essential, and would improve standards of care whilst creating a foundation of data on which continuing improvements

in the outcome of health interventions can occur – i.e.,

sustainability

Propositions - 3Propositions - 3

Drug development is not the highest priority in low resource settings, and

phase I clinical trials initiated by international pharmaceutical

companies should address the additional ethical issues that are

created (benefit to study population)

Propositions - 4Propositions - 4

Evidence collected in high income countries is directed towards their

own problems in the context of their populations, environments and

available resources. Not all of this can be assumed to be generalizable

and there will be inevitable gaps

Questions - 1Questions - 1

What are the advantages and disadvantages of clinical research

versus the use of clinical guidelines in improving care (early detection

and treatment) in developing countries?

Questions - 2Questions - 2

How can clinical research be promoted and the necessary

infrastructure built in countries with limited resources?

The Problem: a Vicious The Problem: a Vicious CycleCycle

Limited Resource

s

Many Patients With Advanced

Disease and Many Potential

Patients

LOW CAPACITY

POOR ACCESS

High Mortality Rate

Unmet need for terminal

care

Quantitative Quantitative LimitationsLimitations

Limited numbers of cancer specialistsLimited numbers of cancer specialists (but (but some centers of excellence): number of some centers of excellence): number of patients overwhelmingpatients overwhelming

Few specialized facilitiesFew specialized facilities: limitations in : limitations in drugs and equipment (availability, cost drugs and equipment (availability, cost and maintenance)and maintenance)

Public and academic salaries lowPublic and academic salaries low : many : many seek some or full-time private practice, seek some or full-time private practice, often out of necessityoften out of necessity

Bright students go or sent for training Bright students go or sent for training overseasoverseas: many are permanently lost: many are permanently lost

Qualitative LimitationsQualitative Limitations

Cancer often not considered by primary health Cancer often not considered by primary health personnel, or fatalistic attitude inhibits referralpersonnel, or fatalistic attitude inhibits referral

Training often of poor quality and ceases after Training often of poor quality and ceases after medical school (little or no continuing education)medical school (little or no continuing education)

Medicine often eminence-based, not evidence-Medicine often eminence-based, not evidence-based based

Minimal discipline in implementation of Minimal discipline in implementation of interventions since limited supervision and interventions since limited supervision and accountability; no incentive to follow up or record accountability; no incentive to follow up or record outcomeoutcome

Nursing, pharmacy, blood banks etc. often Nursing, pharmacy, blood banks etc. often inadequate and non-medical staff generally inadequate and non-medical staff generally ineffectively utilized (no specialist nurses, for ineffectively utilized (no specialist nurses, for example)example)

Factors Limiting Factors Limiting Access Access

Poverty and ignorance delay seeking helpPoverty and ignorance delay seeking help Primary (and secondary) care suboptimal: Primary (and secondary) care suboptimal:

lack of focus and knowledge about cancer lack of focus and knowledge about cancer leads to misdiagnosis and misinformationleads to misdiagnosis and misinformation

Few centers: average journey long (cost) Few centers: average journey long (cost) Result : late diagnosis; advanced diseaseResult : late diagnosis; advanced disease

Limitations in Limitations in Resources for Cancer Resources for Cancer TherapyTherapy In Dec 2004, there were approximately In Dec 2004, there were approximately

2500 radiotherapy centers and 3700 2500 radiotherapy centers and 3700 machines for cancer therapy (enough for machines for cancer therapy (enough for 1.85 million patients per year compared to 1.85 million patients per year compared to 3 million who need it. Maldistribution: >20 3 million who need it. Maldistribution: >20 countries have none. (DIRAC) countries have none. (DIRAC)

In 2000 the USA accounted for 60% of In 2000 the USA accounted for 60% of anti-cancer drug sales, Europe, 19% and anti-cancer drug sales, Europe, 19% and Japan, 16%. The rest of the world, 5%. Japan, 16%. The rest of the world, 5%. (IMS)(IMS)

Leakage of Talent to the Leakage of Talent to the USAUSA

All India Institute of Medical Science:

56% of medical graduates emigrated from 1956-80, 49% in the 1990s

30% of Mexicans with PhD’s are in the USA

The 1million Indians in the USA account for 0.1% of India's population but the equivalent of 10% of India's total income

Source: Annual Report, 2005, Nursing and Midwifery Council, UK

Nurses who joined the UK Nurses who joined the UK register from countries from register from countries from which recruitment is banned which recruitment is banned (2004-5)(2004-5) South Africa South Africa 933933 Nigeria Nigeria 466466 West Indies West Indies 352352 Zimbabwe Zimbabwe 311311 Ghana Ghana 272272 Pakistan Pakistan 205205 Zambia Zambia 162162 Mauritius Mauritius 102102

Kenya Kenya 9999 Botswana Botswana 9191 Nepal Nepal 7373 SwazilandSwaziland 6969 MalawiMalawi 5252 Sri Lanka Sri Lanka 4747 LesothoLesotho 4343 Sierra LeoneSierra Leone 2424

Total 3301 Initial Registrants: 33,257; Overseas (non-EU): 11,477 India: 3,690; Philippines: 2,521; Nigeria: 466;

The Solution: Build The Solution: Build CapacityCapacity

Less Limited

Resources

Fewer Patients with More

Limited Disease and Fewer Potential Patients

Prevention

Education

Screening

GREATER CAPACITY

IMPROVED ACCESS

Lower Mortality Rate

Less need and

greater capacity

for terminal

care

Capacity BuildingCapacity Building

Improve quality of existing human, and to Improve quality of existing human, and to the extent possible, material resourcesthe extent possible, material resources– This will require training, at least of the national This will require training, at least of the national

and regional leaders in “scientific medicine”and regional leaders in “scientific medicine” Expand by training more graduates in Expand by training more graduates in

health related disciplines and creating health related disciplines and creating centers for specialist trainingcenters for specialist training

Lessen loss to academic medicine by Lessen loss to academic medicine by improving professional and economic improving professional and economic circumstances – outside assistance circumstances – outside assistance essentialessential

Why do Clinical Trials Why do Clinical Trials in Low Resource in Low Resource Settings?Settings?

1.1. An ability to conduct research is An ability to conduct research is essential to the development of a high essential to the development of a high quality, sustainable, health systemquality, sustainable, health system

2.2. Scientifically trained physicians are Scientifically trained physicians are more able to learn from existing more able to learn from existing sources of information – the literature, sources of information – the literature, web-based information, meetings etc.web-based information, meetings etc.

Why do Clinical Trials Why do Clinical Trials in Low Resource in Low Resource Settings?Settings?

3.3. To accumulate data that allows the To accumulate data that allows the efficacy and cost-benefit ratio efficacy and cost-benefit ratio ((efficiencyefficiency) of any feasible interventions ) of any feasible interventions in the natural history of a disease to be in the natural history of a disease to be assessed assessed

4.4. Because evidence is Because evidence is context sensitive – context sensitive – therefore, what applies in one therefore, what applies in one population or environment does not population or environment does not necessarily apply in anothernecessarily apply in another

Why do Clinical Trials Why do Clinical Trials in Low Resource in Low Resource Settings?Settings?

5.5. The questions (hypotheses) that need to be The questions (hypotheses) that need to be addressed to improve care in low resource addressed to improve care in low resource settings frequently differ from those that settings frequently differ from those that are given highest priority in high resource are given highest priority in high resource settings settings

6.6. More than half of all cancer is in developing More than half of all cancer is in developing countries – this represents a valuable, but countries – this represents a valuable, but largely untapped source of potentially largely untapped source of potentially unique knowledge of value to allunique knowledge of value to all

In Addition, Clinical In Addition, Clinical Trials Can:Trials Can: Simultaneously provide effective Simultaneously provide effective

prevention or treatmentprevention or treatment Provide a focus for training and education Provide a focus for training and education Improve clinical care – quality assurance Improve clinical care – quality assurance

needs (monitoring and audits) detect needs (monitoring and audits) detect problems, provide supervision; instill problems, provide supervision; instill good practices good practices

Provide improved professional Provide improved professional circumstances and new career circumstances and new career opportunities – with added incentives to opportunities – with added incentives to improve resultsimprove results

Phase II/III Clinical Phase II/III Clinical Trials can Improve Trials can Improve CareCare Clinical research demands high standards of Clinical research demands high standards of

care and expertise in the disease in question:care and expertise in the disease in question:– Accurate diagnosisAccurate diagnosis– Appropriate treatment (or early detection) designAppropriate treatment (or early detection) design– Discipline in adhering to protocol; good supportive Discipline in adhering to protocol; good supportive

carecare– Documentation of results (follow up essential)Documentation of results (follow up essential)– Quality assurance – of care and dataQuality assurance – of care and data

Studies must be designed with available Studies must be designed with available resources and study populations in mind resources and study populations in mind

Performing clinical trials will help to identify Performing clinical trials will help to identify infrastructural inadequacies, stimulate the infrastructural inadequacies, stimulate the search for solutions and increase precision and search for solutions and increase precision and disciplinediscipline

Ethical principles must be adhered toEthical principles must be adhered to

Examples of Clinical Trials Examples of Clinical Trials that Result in Improved that Result in Improved CareCare Comparison of relative toxicity, cost or Comparison of relative toxicity, cost or

scheduling of standard regimens scheduling of standard regimens optimization studies optimization studies

Identification of risk factors in a local Identification of risk factors in a local context, or characterization of disease or context, or characterization of disease or its epidemiology (generally one arm its epidemiology (generally one arm studies)studies)

Early detection studies, particularly using Early detection studies, particularly using direct visualization techniques and simple direct visualization techniques and simple treatment strategies of early lesionstreatment strategies of early lesions

Value of Inter-Value of Inter-Institutional Clinical Institutional Clinical ProjectsProjects Improved access of patients and Improved access of patients and

professionals to the local (few) and professionals to the local (few) and international experts:international experts:

Increased communication and hence Increased communication and hence learning among all participants learning among all participants (community of practice)(community of practice)

Greater acceptability of quality control Greater acceptability of quality control potentially healthy competition among potentially healthy competition among participating institutionsparticipating institutions

May identify problems that are specific May identify problems that are specific to populations, regions or institutionsto populations, regions or institutions

High Priority Clinical High Priority Clinical Trials in Low Resource Trials in Low Resource SettingsSettings

Questions of national or local importance:Questions of national or local importance:– Treatment of high priority diseases; high incidence Treatment of high priority diseases; high incidence

with a known effective intervention (may be with a known effective intervention (may be uncommon in the affluent world (e.g. hepatoma, uncommon in the affluent world (e.g. hepatoma, bilharzial bladder cancer) bilharzial bladder cancer) Preventable or curablePreventable or curable

Study of toxicity, efficacy and practicality of Study of toxicity, efficacy and practicality of therapies developed in high income countriestherapies developed in high income countries

Impact of resource sparing modifications Impact of resource sparing modifications (detection methods, e.g., VIA, VILI, altered drug (detection methods, e.g., VIA, VILI, altered drug regimens or X-ray fields, simpler surgery)regimens or X-ray fields, simpler surgery)

Standard therapies associated with evaluation Standard therapies associated with evaluation of risk factors, characterization or epidemiology of risk factors, characterization or epidemiology

Developing Necessary Developing Necessary InfrastructureInfrastructure Will nearly always require international Will nearly always require international

collaboration – ideally, direct collaboration – ideally, direct participationparticipation– To provide the necessary propositional and To provide the necessary propositional and

procedural knowledgeprocedural knowledge– To provide training and education To provide training and education – To monitor conformity to protocol, quality To monitor conformity to protocol, quality

of data and confirm results of the of data and confirm results of the interventionintervention

– To encourage inter-departmental and To encourage inter-departmental and inter-institutional collaborationinter-institutional collaboration

Benefits to AllBenefits to All

Translational and clinical research will be more Translational and clinical research will be more rapidly accomplished if a larger number of rapidly accomplished if a larger number of patients were accessible (applies particularly patients were accessible (applies particularly to uncommon cancers or stages of cancer)to uncommon cancers or stages of cancer)

Developing countries provide unique Developing countries provide unique opportunities for understanding the opportunities for understanding the epidemiology and pathogenesis of cancer and epidemiology and pathogenesis of cancer and exploring the efficacy of low cost or resource exploring the efficacy of low cost or resource sparing interventions sparing interventions

Research in developing countries may be Research in developing countries may be relevant to minority populations in affluent relevant to minority populations in affluent countriescountries

Obstacles to Research Obstacles to Research in Developing in Developing CountriesCountries Little or no research training of Little or no research training of

physicians; promotion generally based physicians; promotion generally based on seniorityon seniority

Protocols often viewed as guidelines Protocols often viewed as guidelines which can be modified at will which can be modified at will

Limited research infrastructureLimited research infrastructure– Concept of data quality rudimentaryConcept of data quality rudimentary– Published data often unreliablePublished data often unreliable

Lack of professional or financial rewards: Lack of professional or financial rewards: lack of incentive to perform research lack of incentive to perform research

Can be seen as “limiting” freedom Can be seen as “limiting” freedom Follow up often poorFollow up often poor

Knowledge Transfer: Knowledge Transfer: The Standard ModelThe Standard Model High level meetings in developing High level meetings in developing

countries (with predominantly Western countries (with predominantly Western faculty)faculty)– Utility depends on content, but audience Utility depends on content, but audience

unselected and no outcome measures unselected and no outcome measures Training in Western institutionsTraining in Western institutions

– Benefits the West more than low and middle Benefits the West more than low and middle income countries, although has created some income countries, although has created some excellent leaders in developing countriesexcellent leaders in developing countries

Provision of written guidelinesProvision of written guidelines– Essential, assuming based on relevant Essential, assuming based on relevant

evidence, but limited or no assessment of use evidence, but limited or no assessment of use or valueor value

Communicating Communicating InformationInformation

Sender – information put in language that recipient understands

Recipient – must have sufficient experience for information to be meaningful

Information of no value unless acted upon

Standard Model; Standard Model; GuidelinesGuidelines Many organizations develop “best Many organizations develop “best

practice guidelines” practice guidelines” – May be created with minimal knowledge of May be created with minimal knowledge of

local resources and populations local resources and populations (feasibility?)(feasibility?)– Based on information derived, for the most Based on information derived, for the most

part, from high income countries part, from high income countries (applicability?)(applicability?)

– Read only by a small fraction of practitioners Read only by a small fraction of practitioners and not necessarily used as written – and not necessarily used as written – (utility?)(utility?)

Usually no measures of use, performance Usually no measures of use, performance or outcome (i.e. or outcome (i.e. evidenceevidence of utility) of utility)

May be used by non-specialists with the May be used by non-specialists with the potential for serious harmpotential for serious harm

Applicability of Applicability of Guidelines Guidelines The pattern of disease differsThe pattern of disease differs – incidence and – incidence and

stage distribution (different priorities re: cancers stage distribution (different priorities re: cancers to be studied) to be studied)

Cancer biology may differCancer biology may differ – e.g., bilharzial – e.g., bilharzial associated bladder cancer (different approaches associated bladder cancer (different approaches to prevention or treatment), genetic lesions may to prevention or treatment), genetic lesions may differdiffer

Resources and facilities differResources and facilities differ – differences in – differences in staff expertise, and availability or access to staff expertise, and availability or access to products products

Patients differPatients differ - illiteracy and poverty impact - illiteracy and poverty impact upon adherence to treatment, genetic and upon adherence to treatment, genetic and environmental factors (pharmacogenetics, environmental factors (pharmacogenetics, comorbidities, malnutrition, hygiene) may comorbidities, malnutrition, hygiene) may change outcomechange outcome

Clinical Trials Actively Clinical Trials Actively Build CapacityBuild Capacity

Training/continuing education can be Training/continuing education can be accomplished accomplished in the context of clinical in the context of clinical trialstrials for health professionals for health professionals

Infrastructure is developed, with Infrastructure is developed, with additional staff, improved use of IT etc. additional staff, improved use of IT etc. that should impact on non-research that should impact on non-research clinical careclinical care

Trials foster collaboration and Trials foster collaboration and communication, both nationally and communication, both nationally and internationallyinternationally

Quality assurance provides an assessment Quality assurance provides an assessment of effectiveness of educational methodsof effectiveness of educational methods

Comparison of Comparison of Guidelines and Clinical Guidelines and Clinical TrialsTrials

Designed for a specific Designed for a specific population in the context of population in the context of available resourceavailable resource

Usually entails collaboration Usually entails collaboration and mutual learningand mutual learning

Associated with quality Associated with quality assurance and ethical assurance and ethical reviewreview

Identifies deficienciesIdentifies deficiencies Associated with outcome Associated with outcome

measuresmeasures Generates new informationGenerates new information

Based on available Based on available evidence – usually from evidence – usually from a high resource context a high resource context

Rarely entails Rarely entails collaboration or learningcollaboration or learning

Rarely any quality control Rarely any quality control and no ethical reviewand no ethical review

No identification of No identification of deficienciesdeficiencies

No outcome measuresNo outcome measures No new information No new information

Research

Guidelines

Dialogue; the Dialogue; the Importance of Mutual Importance of Mutual UnderstandingUnderstanding

1. LISTEN: Chinese character includes those for heart, eye and ear

2. LEADS TO: deeper understanding and a sense of shared meaning

Dialogue: from Greek dia: across, logos: word,

The Sage, the person of wisdom, for whom knowledge is sacred is the fount of knowledge

Listen

Sage

Advantages and Advantages and Opportunities re: Opportunities re: Cooperative Trials in LRSCooperative Trials in LRS Improved access of patients and Improved access of patients and

professionals to the limited number of professionals to the limited number of experts involved in conduct of the trialexperts involved in conduct of the trial

Increased communication and hence Increased communication and hence learning among all participantslearning among all participants

Instills good habits of clinical care, and a Instills good habits of clinical care, and a research perspective in junior staff that research perspective in junior staff that extends beyond the trial in questionextends beyond the trial in question

Provides a local data base that can be Provides a local data base that can be built upon – a step towards sustainabilitybuilt upon – a step towards sustainability

Cooperative Groups in Cooperative Groups in Low Resource Settings - Low Resource Settings - ForeignForeign

Can join existing groups based in Can join existing groups based in affluent countries but…affluent countries but…– Trials will not address locally important Trials will not address locally important

problemsproblems– Patients may not be comparable to those Patients may not be comparable to those

entered in a “western” settingentered in a “western” setting– Limited opportunities to play a role in Limited opportunities to play a role in

identifying or designing studiesidentifying or designing studies– Resources provided to group members in Resources provided to group members in

the wealthy country may not be availablethe wealthy country may not be available– Regulatory issues can create problemsRegulatory issues can create problems

Cooperative Groups in Cooperative Groups in Low Resource Settings - Low Resource Settings - LocalLocal

Can develop own groups but…Can develop own groups but…– May lack appropriate leadershipMay lack appropriate leadership– Inter-institutional rivalries may existInter-institutional rivalries may exist– Entrenched views of senior members Entrenched views of senior members

of institutions (lack of academic of institutions (lack of academic mindset) may limit studies that can be mindset) may limit studies that can be donedone

– Will usually have limited infrastructure Will usually have limited infrastructure and ability to monitor qualityand ability to monitor quality

– Therefore: will usually require outside Therefore: will usually require outside assistanceassistance

Cooperative Groups in Cooperative Groups in Low Resource SettingsLow Resource Settings

Most cooperative groups in developing Most cooperative groups in developing countries are in more advanced countries countries are in more advanced countries such as Latin Americasuch as Latin America– GATLA, GATHEM for hematological neoplasmsGATLA, GATHEM for hematological neoplasms

Some relationships between US or Some relationships between US or European Groups have been establishedEuropean Groups have been established

Collaboration with external organizations Collaboration with external organizations or institutions who support the or institutions who support the development of local groups increasing development of local groups increasing (e.g., INCTR)(e.g., INCTR)

Who Pays for Who Pays for Research?Research? The consumerThe consumer – especially when combined with – especially when combined with

appropriate therapyappropriate therapy– Out-of-pocket expenses, private or national insuranceOut-of-pocket expenses, private or national insurance

The institutionThe institution – where research is supported by – where research is supported by grants, and/or institution is academic (education)grants, and/or institution is academic (education)

Charitable organizations/NGOsCharitable organizations/NGOs – which provide – which provide funds for disciplined patient treatment, funds for disciplined patient treatment, professional education or research (not for professional education or research (not for individuals)individuals)

Government or Governmental OrganizationsGovernment or Governmental Organizations – – particularly when health/economic (closely particularly when health/economic (closely linked) or international political benefit may linked) or international political benefit may result from the research or trainingresult from the research or training

The Pharmaceutical industryThe Pharmaceutical industry – drug development – drug development

Pharma Sponsored Pharma Sponsored TrialsTrials If international pharmaceutical sponsor, If international pharmaceutical sponsor,

ultimately directed to increased drug sales ultimately directed to increased drug sales (initial incentives, e.g., donations of drugs or (initial incentives, e.g., donations of drugs or funds may be valuable)funds may be valuable)

Post-trial local price and availability are issues Post-trial local price and availability are issues that should be addressed in drug development that should be addressed in drug development trialstrials– Is it sufficient for only high income patients in the Is it sufficient for only high income patients in the

country to benefit?country to benefit?– Need to avoid charges of exploitation – esp. phase I Need to avoid charges of exploitation – esp. phase I

Can help to improve infrastructure and provide Can help to improve infrastructure and provide additional revenue for hospitalsadditional revenue for hospitals

Patients can benefit if trials address important Patients can benefit if trials address important local problems as well as special ethical local problems as well as special ethical considerationsconsiderations

Local Pharma IndustryLocal Pharma Industry

Local pharmaceutical industries are Local pharmaceutical industries are growinggrowing

Local drugs much less expensive – Indian Local drugs much less expensive – Indian drugs now used widely in Asia and Africa; drugs now used widely in Asia and Africa; government subsidiesgovernment subsidies

Increasing local development pipe-line Increasing local development pipe-line with increased local needs for clinical with increased local needs for clinical trials, including phase I studiestrials, including phase I studies

May push international pharmaceutical May push international pharmaceutical companies out of the huge market in companies out of the huge market in developing countries (at least for generics) developing countries (at least for generics) – 55% or so of all cancer and climbing– 55% or so of all cancer and climbing

Sponsorship by NGOsSponsorship by NGOs

Most cancer societies not involved in Most cancer societies not involved in patient care, but may support salaries or patient care, but may support salaries or provide grantsprovide grants

Some professional societies may sponsor Some professional societies may sponsor studies studies – SIOP; Wilms’, hepatoblastomaSIOP; Wilms’, hepatoblastoma

INCTR dedicated to cancer in developing INCTR dedicated to cancer in developing countries: support; NCI, grants, Pharmacountries: support; NCI, grants, Pharma– Clinical trials used to both immediately Clinical trials used to both immediately

improve patient care and as a focus for improve patient care and as a focus for capacity buildingcapacity building

INCTR’s NetworkINCTR’s Network

Offices and Branches

Collaborating Units

Tenets of the NetworkTenets of the Network

Focused on small number of centers in Focused on small number of centers in countries interested in clinical research and countries interested in clinical research and training programstraining programs

Includes active participation in identification Includes active participation in identification and design of projectsand design of projects

Works with other organizations with Works with other organizations with overlapping interests overlapping interests

Once studies running effectively, add additional Once studies running effectively, add additional centers: use participating centers to provide centers: use participating centers to provide training for others in the country or regiontraining for others in the country or region

Modern capabilities re: IT for training, Modern capabilities re: IT for training, consultation, review of diagnostic images etc. consultation, review of diagnostic images etc. gradually being enhancedgradually being enhanced

Active Clinical ProjectsActive Clinical Projects

Reasons for late presentation of retinoblastoma – 16 Reasons for late presentation of retinoblastoma – 16 centers in 11 countriescenters in 11 countries

Survey of breast cancer management - 4 countries Survey of breast cancer management - 4 countries Cx Cancer screening (with IARC) – 2 countries, 4 sitesCx Cancer screening (with IARC) – 2 countries, 4 sites Treatment of advanced cervical cancer (with Eli Lilly) – Treatment of advanced cervical cancer (with Eli Lilly) –

10 centers in 10 countries (accrual complete)10 centers in 10 countries (accrual complete) Treatment and study of ALL in India - 4 Indian centersTreatment and study of ALL in India - 4 Indian centers Treatment and study of Burkitt’s Lymphoma in Africa - Treatment and study of Burkitt’s Lymphoma in Africa -

4 centers in 3 countries (expanded access in Tanzania)4 centers in 3 countries (expanded access in Tanzania) Palliative care; provision and training – 4 countriesPalliative care; provision and training – 4 countries Expansion of care for leukemia (Philippines)Expansion of care for leukemia (Philippines)

Projects in Planning Projects in Planning Phase Phase Treatment of locally advanced Treatment of locally advanced

retinoblastoma (Philippines, Turkey)retinoblastoma (Philippines, Turkey) Treatment of breast cancer (with Treatment of breast cancer (with

IAEA)IAEA) Cervical cancer screening and Cervical cancer screening and

treatment treatment Palliative care in Nicaragua (PACT)Palliative care in Nicaragua (PACT) Cancer control in CameroonCancer control in Cameroon Cancer control in UzbekistanCancer control in Uzbekistan

DELHI

CHENNAI (168)

o DELHI (232)

MUMBAI (652)

Acute Lymphoblastic Leukemia

ALL study: 1048 ALL study: 1048 PatientsPatients

Acute Lymphoblastic Leukemia (MCP 841)

OAS (1986-89)

Years

14121086420

Su

rviv

al

1.0

.9

.8

.7

.6

.5

.4

.3

.2

.1

0.0

OAS 43.2 %n=205

Acute Lymphoblastic Leukemia (MCP 841)

OAS (1990-94)

YEARS

121086420

Su

rviv

al

1.0

.9

.8

.7

.6

.5

.4

.3

.2

.1

0.0

OAS 58 %n=412

Acute Lymphoblstic Leukemia (MCP 841)

OAS (1986-98)

Years

14121086420

Su

rviv

al

1.0

.9

.8

.7

.6

.5

.4

.3

.2

.1

0.0

OAS 58.48%

Acute Lymphoblastic Leukemia (MCP 841)

OAS (1995-98)

OASYRS

76543210

Su

rviv

al

1.0

.9

.8

.7

.6

.5

.4

.3

.2

.1

0.0

OAS 72.57 %

Improvement over time with MCP 841 at TMH

Research ProjectsResearch Projects

PROJECTSINCTR Programs, Branches, Associate Members, Partners

Disease Specific Strategy Groups

Scientific Review

Ethical Review

Implementation

Strategy GroupsStrategy Groups

International groups identify and implement disease specific activities in prevention, treatment, education

Cx Cancer, August 2004

Implementation Meeting, African BL, Tanzania, August 2004

Clinical Trials Clinical Trials WorkshopsWorkshops Provide basic information on Provide basic information on

clinical trials in cancer prevention clinical trials in cancer prevention and treatmentand treatment

Associated with training of data Associated with training of data managers managers

Supported by pharmaceutical Supported by pharmaceutical industryindustry

Held in China and Brazil to dateHeld in China and Brazil to date

Educational MeetingsEducational Meetings

Workshops and training courses

Jordan, Iraqi Ped Onc Workshop, April 2004

Nurses Oncology Training, Cairo, October 2003

Includes courses in GCP

Expert VisitsExpert Visits

Experts spend time in centers to teach, learn, and in some cases help establish programs

Stuart Brown, Palliative Care, Nepal, August 2003

Can be supplemented by electives for trainees and long term stays where feasible – MERGES WITH TWINNING PROGRAMS

StrategiesStrategies

Will need to develop training courses Will need to develop training courses in both clinical science (oncology) and in both clinical science (oncology) and infrastructure required for trials infrastructure required for trials management, including CTO’smanagement, including CTO’s

Accreditation of individuals and Accreditation of individuals and institutions would be valuableinstitutions would be valuable

Continuing education essentialContinuing education essential A system of monitoring will need to be A system of monitoring will need to be

put in placeput in place

Expanding AccessExpanding Access

Create centers in appropriate institutions Create centers in appropriate institutions that can participate in projects that that can participate in projects that encompass research, service provision and encompass research, service provision and the simultaneous provision of training and the simultaneous provision of training and education to provide a FOCUSeducation to provide a FOCUS

Develop a plan for creating satellite centers Develop a plan for creating satellite centers such that KSD and research are expanded such that KSD and research are expanded within the country in a coordinated fashionwithin the country in a coordinated fashion

Maximize in-country training; utilize where Maximize in-country training; utilize where necessary training in established centers in necessary training in established centers in other developing countries of similar SESother developing countries of similar SES

Maximizing IT - 2006Maximizing IT - 2006

Telesynergy or Telesynergy or internet-based internet-based lectures, focused lectures, focused meetings and meetings and training coursestraining courses

Use of PORTAL for Use of PORTAL for Staff WorkspacesStaff Workspaces

Use of PORTAL for Use of PORTAL for discussions, discussions, surveys & free surveys & free contributionscontributions

Communication ToolsCommunication Tools

Newsletter: NETWORK

NETWORK Workspace

Admin. Workspace

Education Site Member’s Forum Annual Meet. Workspace

Strategy for Strategy for SustainabilitySustainability In country training with hands-on experience: In country training with hands-on experience:

long term collaborative research projectslong term collaborative research projects with with immediate benefits to patientsimmediate benefits to patients– Clinical trials of locally relevant approaches to Clinical trials of locally relevant approaches to

screening and treatment provide improved care as screening and treatment provide improved care as well as professional educationwell as professional education

– Development of training centers that will expand the Development of training centers that will expand the workforce and increase access to care in the country workforce and increase access to care in the country or regionor region

Education and training built around projectsEducation and training built around projects– Training in scientific methodology: enhanced Training in scientific methodology: enhanced

professional experience; independenceprofessional experience; independence Information collected provides a foundation on Information collected provides a foundation on

which to build future endeavorswhich to build future endeavors

Evidence Based Cancer Evidence Based Cancer Control – Multiple Control – Multiple BenefitsBenefits INCTR is working with Cochrane INCTR is working with Cochrane

Cancer Network and other partners to:Cancer Network and other partners to:– Catalogue available evidence from Catalogue available evidence from

developing countriesdeveloping countries– Develop a training program for secondary Develop a training program for secondary

review (and therefore, disease experts)review (and therefore, disease experts)– Create a data base of secondary reviewsCreate a data base of secondary reviews– Identify gaps in knowledge and promote Identify gaps in knowledge and promote

clinical trials to fill themclinical trials to fill them

““Secondary” ResearchSecondary” Research

Knowledge of existing literature is Knowledge of existing literature is essential in order to decide which essential in order to decide which questions are worth answering (the “art” questions are worth answering (the “art” of science)of science)

Training in the evaluation of published Training in the evaluation of published research provides an understanding of research provides an understanding of the scientific method in a clinical contextthe scientific method in a clinical context

Thus, an important part of education in Thus, an important part of education in the conduct of clinical trials and the conduct of clinical trials and sustainability sustainability

Summary and Summary and ConclusionsConclusions Clinical trials essential in developing countries: Clinical trials essential in developing countries:

– Outcomes of interventions may differ from those in Outcomes of interventions may differ from those in affluent populations – new evidence base requiredaffluent populations – new evidence base required

– Best interventions may differ from rich countries because Best interventions may differ from rich countries because of toxicity, cost or limited access (expertise, materials)of toxicity, cost or limited access (expertise, materials)

– Clinical trials can be a focus for building capacity, and can Clinical trials can be a focus for building capacity, and can lead to immediate patient benefits while building a lead to immediate patient benefits while building a foundation of data on which to make further progress foundation of data on which to make further progress

Collaboration between governments, corporations Collaboration between governments, corporations and NGOs (including academia) should be and NGOs (including academia) should be mutually beneficial and benefit patients mutually beneficial and benefit patients everywhereeverywhere

Scientific training is best done via “hands-on” Scientific training is best done via “hands-on” training in both primary and secondary researchtraining in both primary and secondary research