clinical trials in low resource settings ian magrath
TRANSCRIPT
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