Clinical Trials in Low Resource Settings Ian Magrath

Outline Propositions Questions Problems faced in developing countries Addressing the Problems: Role of Clinical Trials Infrastructure: knowledge transfer Who pays?: sponsorships INCTR Strategies Conclusions

Propositions -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 - 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 - 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 - 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 - 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 - 2 How can clinical research be promoted and the necessary infrastructure built in countries with limited resources?

The Problem: a Vicious Cycle Limited Resources Many Patients With Advanced Disease and Many Potential Patients LOW CAPACITY POOR ACCESS High Mortality Rate Unmet need for terminal care

Quantitative Limitations Limited numbers of cancer specialists (but some centers of excellence): number of patients overwhelming Limited numbers of cancer specialists (but some centers of excellence): number of patients overwhelming Few specialized facilities: limitations in drugs and equipment (availability, cost and maintenance) Few specialized facilities: limitations in drugs and equipment (availability, cost and maintenance) Public and academic salaries low : many seek some or full-time private practice, often out of necessity Public and academic salaries low : many seek some or full-time private practice, often out of necessity Bright students go or sent for training overseas: many are permanently lost Bright students go or sent for training overseas: many are permanently lost

Qualitative Limitations Cancer often not considered by primary health personnel, or fatalistic attitude inhibits referral Cancer often not considered by primary health personnel, or fatalistic attitude inhibits referral Training often of poor quality and ceases after medical school (little or no continuing education) Training often of poor quality and ceases after medical school (little or no continuing education) Medicine often eminence-based, not evidence-based Medicine often eminence-based, not evidence-based Minimal discipline in implementation of interventions since limited supervision and accountability; no incentive to follow up or record outcome Minimal discipline in implementation of interventions since limited supervision and accountability; no incentive to follow up or record outcome Nursing, pharmacy, blood banks etc. often inadequate and non-medical staff generally ineffectively utilized (no specialist nurses, for example) Nursing, pharmacy, blood banks etc. often inadequate and non-medical staff generally ineffectively utilized (no specialist nurses, for example)

Factors Limiting Access Poverty and ignorance delay seeking help Poverty and ignorance delay seeking help Primary (and secondary) care suboptimal: lack of focus and knowledge about cancer leads to misdiagnosis and misinformation Primary (and secondary) care suboptimal: lack of focus and knowledge about cancer leads to misdiagnosis and misinformation Few centers: average journey long (cost) Few centers: average journey long (cost) Result : late diagnosis; advanced disease Result : late diagnosis; advanced disease

Limitations in Resources for Cancer Therapy In Dec 2004, there were approximately 2500 radiotherapy centers and 3700 machines for cancer therapy (enough for 1.85 million patients per year compared to 3 million who need it. Maldistribution: >20 countries have none. (DIRAC) In Dec 2004, there were approximately 2500 radiotherapy centers and 3700 machines for cancer therapy (enough for 1.85 million patients per year compared to 3 million who need it. Maldistribution: >20 countries have none. (DIRAC) In 2000 the USA accounted for 60% of anti- cancer drug sales, Europe, 19% and Japan, 16%. The rest of the world, 5%. (IMS) In 2000 the USA accounted for 60% of anti- cancer drug sales, Europe, 19% and Japan, 16%. The rest of the world, 5%. (IMS)

Leakage of Talent to the USA All India Institute of Medical Science: 56% of medical graduates emigrated from , 49% in the 1990s 30% of Mexicans with PhDs 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 register from countries from which recruitment is banned (2004-5) South Africa 933 South Africa 933 Nigeria 466 Nigeria 466 West Indies 352 West Indies 352 Zimbabwe 311 Zimbabwe 311 Ghana 272 Ghana 272 Pakistan 205 Pakistan 205 Zambia 162 Zambia 162 Mauritius 102 Mauritius 102 Kenya 99 Kenya 99 Botswana 91 Botswana 91 Nepal 73 Nepal 73 Swaziland69 Swaziland69 Malawi52 Malawi52 Sri Lanka 47 Sri Lanka 47 Lesotho43 Lesotho43 Sierra Leone24 Sierra Leone24 Total 3301 Initial Registrants: 33,257; Overseas (non-EU): 11,477 India: 3,690; Philippines: 2,521; Nigeria: 466;

The Solution: Build Capacity 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 Building Improve quality of existing human, and to the extent possible, material resources Improve quality of existing human, and to the extent possible, material resources –This will require training, at least of the national and regional leaders in scientific medicine Expand by training more graduates in health related disciplines and creating centers for specialist training Expand by training more graduates in health related disciplines and creating centers for specialist training Lessen loss to academic medicine by improving professional and economic circumstances – outside assistance essential Lessen loss to academic medicine by improving professional and economic circumstances – outside assistance essential

Why do Clinical Trials in Low Resource Settings? 1. An ability to conduct research is essential to the development of a high quality, sustainable, health system 2. Scientifically trained physicians are more able to learn from existing sources of information – the literature, web-based information, meetings etc.

Why do Clinical Trials in Low Resource Settings? 3. To accumulate data that allows the efficacy and cost-benefit ratio (efficiency) of any feasible interventions in the natural history of a disease to be assessed 4. Because evidence is context sensitive – therefore, what applies in one population or environment does not necessarily apply in another

Why do Clinical Trials in Low Resource Settings? 5. The questions (hypotheses) that need to be addressed to improve care in low resource settings frequently differ from those that are given highest priority in high resource settings 6. More than half of all cancer is in developing countries – this represents a valuable, but largely untapped source of potentially unique knowledge of value to all

In Addition, Clinical Trials Can: Simultaneously provide effective prevention or treatment Simultaneously provide effective prevention or treatment Provide a focus for training and education Provide a focus for training and education Improve clinical care – quality assurance needs (monitoring and audits) detect problems, provide supervision; instill good practices Improve clinical care – quality assurance needs (monitoring and audits) detect problems, provide supervision; instill good practices Provide improved professional circumstances and new career opportunities – with added incentives to improve results Provide improved professional circumstances and new career opportunities – with added incentives to improve results

Phase II/III Clinical Trials can Improve Care Clinical research demands high standards of care and expertise in the disease in question: Clinical research demands high standards of care and expertise in the disease in question: –Accurate diagnosis –Appropriate treatment (or early detection) design –Discipline in adhering to protocol; good supportive care –Documentation of results (follow up essential) –Quality assurance – of care and data Studies must be designed with available resources and study populations in mind Studies must be designed with available resources and study populations in mind Performing clinical trials will help to identify infrastructural inadequacies, stimulate the search for solutions and increase precision and discipline Performing clinical trials will help to identify infrastructural inadequacies, stimulate the search for solutions and increase precision and discipline Ethical principles must be adhered to Ethical principles must be adhered to

Examples of Clinical Trials that Result in Improved Care Comparison of relative toxicity, cost or scheduling of standard regimens optimization studies Comparison of relative toxicity, cost or scheduling of standard regimens optimization studies Identification of risk factors in a local context, or characterization of disease or its epidemiology (generally one arm studies) Identification of risk factors in a local context, or characterization of disease or its epidemiology (generally one arm studies) Early detection studies, particularly using direct visualization techniques and simple treatment strategies of early lesions Early detection studies, particularly using direct visualization techniques and simple treatment strategies of early lesions

Value of Inter-Institutional Clinical Projects Improved access of patients and professionals to the local (few) and international experts: Improved access of patients and professionals to the local (few) and international experts: Increased communication and hence learning among all participants (community of practice) Increased communication and hence learning among all participants (community of practice) Greater acceptability of quality control potentially healthy competition among participating institutions Greater acceptability of quality control potentially healthy competition among participating institutions May identify problems that are specific to populations, regions or institutions May identify problems that are specific to populations, regions or institutions

High Priority Clinical Trials in Low Resource Settings Questions of national or local importance: Questions of national or local importance: –Treatment of high priority diseases; high incidence with a known effective intervention (may be uncommon in the affluent world (e.g. hepatoma, bilharzial bladder cancer) Preventable or curable Study of toxicity, efficacy and practicality of therapies developed in high income countries Study of toxicity, efficacy and practicality of therapies developed in high income countries Impact of resource sparing modifications (detection methods, e.g., VIA, VILI, altered drug regimens or X-ray fields, simpler surgery) Impact of resource sparing modifications (detection methods, e.g., VIA, VILI, altered drug regimens or X-ray fields, simpler surgery) Standard therapies associated with evaluation of risk factors, characterization or epidemiology Standard therapies associated with evaluation of risk factors, characterization or epidemiology

Developing Necessary Infrastructure Will nearly always require international collaboration – ideally, direct participation Will nearly always require international collaboration – ideally, direct participation –To provide the necessary propositional and procedural knowledge –To provide training and education –To monitor conformity to protocol, quality of data and confirm results of the intervention –To encourage inter-departmental and inter- institutional collaboration

Benefits to All Translational and clinical research will be more rapidly accomplished if a larger number of patients were accessible (applies particularly to uncommon cancers or stages of cancer) Translational and clinical research will be more rapidly accomplished if a larger number of patients were accessible (applies particularly to uncommon cancers or stages of cancer) Developing countries provide unique opportunities for understanding the epidemiology and pathogenesis of cancer and exploring the efficacy of low cost or resource sparing interventions Developing countries provide unique opportunities for understanding the epidemiology and pathogenesis of cancer and exploring the efficacy of low cost or resource sparing interventions Research in developing countries may be relevant to minority populations in affluent countries Research in developing countries may be relevant to minority populations in affluent countries

Obstacles to Research in Developing Countries Little or no research training of physicians; promotion generally based on seniority Little or no research training of physicians; promotion generally based on seniority Protocols often viewed as guidelines which can be modified at will Protocols often viewed as guidelines which can be modified at will Limited research infrastructure Limited research infrastructure –Concept of data quality rudimentary –Published data often unreliable Lack of professional or financial rewards: lack of incentive to perform research Lack of professional or financial rewards: lack of incentive to perform research Can be seen as limiting freedom Can be seen as limiting freedom Follow up often poor Follow up often poor

Knowledge Transfer: The Standard Model High level meetings in developing countries (with predominantly Western faculty) High level meetings in developing countries (with predominantly Western faculty) –Utility depends on content, but audience unselected and no outcome measures Training in Western institutions Training in Western institutions –Benefits the West more than low and middle income countries, although has created some excellent leaders in developing countries Provision of written guidelines Provision of written guidelines –Essential, assuming based on relevant evidence, but limited or no assessment of use or value

Communicating Information 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; Guidelines Many organizations develop best practice guidelines Many organizations develop best practice guidelines –May be created with minimal knowledge of local resources and populations (feasibility?) –Based on information derived, for the most part, from high income countries (applicability?) –Read only by a small fraction of practitioners and not necessarily used as written – (utility?) Usually no measures of use, performance or outcome (i.e. evidence of utility) Usually no measures of use, performance or outcome (i.e. evidence of utility) May be used by non-specialists with the potential for serious harm May be used by non-specialists with the potential for serious harm

Applicability of Guidelines The pattern of disease differs – incidence and stage distribution (different priorities re: cancers to be studied) The pattern of disease differs – incidence and stage distribution (different priorities re: cancers to be studied) Cancer biology may differ – e.g., bilharzial associated bladder cancer (different approaches to prevention or treatment), genetic lesions may differ Cancer biology may differ – e.g., bilharzial associated bladder cancer (different approaches to prevention or treatment), genetic lesions may differ Resources and facilities differ – differences in staff expertise, and availability or access to products Resources and facilities differ – differences in staff expertise, and availability or access to products Patients differ - illiteracy and poverty impact upon adherence to treatment, genetic and environmental factors (pharmacogenetics, comorbidities, malnutrition, hygiene) may change outcome Patients differ - illiteracy and poverty impact upon adherence to treatment, genetic and environmental factors (pharmacogenetics, comorbidities, malnutrition, hygiene) may change outcome

Clinical Trials Actively Build Capacity Training/continuing education can be accomplished in the context of clinical trials for health professionals Training/continuing education can be accomplished in the context of clinical trials for health professionals Infrastructure is developed, with additional staff, improved use of IT etc. that should impact on non-research clinical care Infrastructure is developed, with additional staff, improved use of IT etc. that should impact on non-research clinical care Trials foster collaboration and communication, both nationally and internationally Trials foster collaboration and communication, both nationally and internationally Quality assurance provides an assessment of effectiveness of educational methods Quality assurance provides an assessment of effectiveness of educational methods

Comparison of Guidelines and Clinical Trials Designed for a specific population in the context of available resource Designed for a specific population in the context of available resource Usually entails collaboration and mutual learning Usually entails collaboration and mutual learning Associated with quality assurance and ethical review Associated with quality assurance and ethical review Identifies deficiencies Identifies deficiencies Associated with outcome measures Associated with outcome measures Generates new information Generates new information Based on available evidence – usually from a high resource context Based on available evidence – usually from a high resource context Rarely entails collaboration or learning Rarely entails collaboration or learning Rarely any quality control and no ethical review Rarely any quality control and no ethical review No identification of deficiencies No identification of deficiencies No outcome measures No outcome measures No new information No new information ResearchGuidelines

Dialogue; the Importance of Mutual Understanding 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 Opportunities re: Cooperative Trials in LRS Improved access of patients and professionals to the limited number of experts involved in conduct of the trial Improved access of patients and professionals to the limited number of experts involved in conduct of the trial Increased communication and hence learning among all participants Increased communication and hence learning among all participants Instills good habits of clinical care, and a research perspective in junior staff that extends beyond the trial in question Instills good habits of clinical care, and a research perspective in junior staff that extends beyond the trial in question Provides a local data base that can be built upon – a step towards sustainability Provides a local data base that can be built upon – a step towards sustainability

Cooperative Groups in Low Resource Settings - Foreign Can join existing groups based in affluent countries but… Can join existing groups based in affluent countries but… –Trials will not address locally important problems –Patients may not be comparable to those entered in a western setting –Limited opportunities to play a role in identifying or designing studies –Resources provided to group members in the wealthy country may not be available –Regulatory issues can create problems

Cooperative Groups in Low Resource Settings - Local Can develop own groups but… Can develop own groups but… –May lack appropriate leadership –Inter-institutional rivalries may exist –Entrenched views of senior members of institutions (lack of academic mindset) may limit studies that can be done –Will usually have limited infrastructure and ability to monitor quality –Therefore: will usually require outside assistance

Cooperative Groups in Low Resource Settings Most cooperative groups in developing countries are in more advanced countries such as Latin America Most cooperative groups in developing countries are in more advanced countries such as Latin America –GATLA, GATHEM for hematological neoplasms Some relationships between US or European Groups have been established Some relationships between US or European Groups have been established Collaboration with external organizations or institutions who support the development of local groups increasing (e.g., INCTR) Collaboration with external organizations or institutions who support the development of local groups increasing (e.g., INCTR)

Who Pays for Research? The consumer – especially when combined with appropriate therapy The consumer – especially when combined with appropriate therapy –Out-of-pocket expenses, private or national insurance The institution – where research is supported by grants, and/or institution is academic (education) The institution – where research is supported by grants, and/or institution is academic (education) Charitable organizations/NGOs – which provide funds for disciplined patient treatment, professional education or research (not for individuals) Charitable organizations/NGOs – which provide funds for disciplined patient treatment, professional education or research (not for individuals) Government or Governmental Organizations – particularly when health/economic (closely linked) or international political benefit may result from the research or training Government or Governmental Organizations – particularly when health/economic (closely linked) or international political benefit may result from the research or training The Pharmaceutical industry – drug development The Pharmaceutical industry – drug development

Pharma Sponsored Trials If international pharmaceutical sponsor, ultimately directed to increased drug sales (initial incentives, e.g., donations of drugs or funds may be valuable) If international pharmaceutical sponsor, ultimately directed to increased drug sales (initial incentives, e.g., donations of drugs or funds may be valuable) Post-trial local price and availability are issues that should be addressed in drug development trials Post-trial local price and availability are issues that should be addressed in drug development trials –Is it sufficient for only high income patients in the country to benefit? –Need to avoid charges of exploitation – esp. phase I Can help to improve infrastructure and provide additional revenue for hospitals Can help to improve infrastructure and provide additional revenue for hospitals Patients can benefit if trials address important local problems as well as special ethical considerations Patients can benefit if trials address important local problems as well as special ethical considerations

Local Pharma Industry Local pharmaceutical industries are growing Local pharmaceutical industries are growing Local drugs much less expensive – Indian drugs now used widely in Asia and Africa; government subsidies Local drugs much less expensive – Indian drugs now used widely in Asia and Africa; government subsidies Increasing local development pipe-line with increased local needs for clinical trials, including phase I studies Increasing local development pipe-line with increased local needs for clinical trials, including phase I studies May push international pharmaceutical companies out of the huge market in developing countries (at least for generics) – 55% or so of all cancer and climbing May push international pharmaceutical companies out of the huge market in developing countries (at least for generics) – 55% or so of all cancer and climbing

Sponsorship by NGOs Most cancer societies not involved in patient care, but may support salaries or provide grants Most cancer societies not involved in patient care, but may support salaries or provide grants Some professional societies may sponsor studies Some professional societies may sponsor studies –SIOP; Wilms, hepatoblastoma INCTR dedicated to cancer in developing countries: support; NCI, grants, Pharma INCTR dedicated to cancer in developing countries: support; NCI, grants, Pharma –Clinical trials used to both immediately improve patient care and as a focus for capacity building

INCTRs Network Offices and BranchesCollaborating Units

Tenets of the Network Focused on small number of centers in countries interested in clinical research and training programs Focused on small number of centers in countries interested in clinical research and training programs Includes active participation in identification and design of projects Includes active participation in identification and design of projects Works with other organizations with overlapping interests Works with other organizations with overlapping interests Once studies running effectively, add additional centers: use participating centers to provide training for others in the country or region Once studies running effectively, add additional centers: use participating centers to provide training for others in the country or region Modern capabilities re: IT for training, consultation, review of diagnostic images etc. gradually being enhanced Modern capabilities re: IT for training, consultation, review of diagnostic images etc. gradually being enhanced

Active Clinical Projects Reasons for late presentation of retinoblastoma – 16 centers in 11 countries Reasons for late presentation of retinoblastoma – 16 centers 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 sites Cx Cancer screening (with IARC) – 2 countries, 4 sites Treatment of advanced cervical cancer (with Eli Lilly) – 10 centers in 10 countries (accrual complete) Treatment of advanced cervical cancer (with Eli Lilly) – 10 centers in 10 countries (accrual complete) Treatment and study of ALL in India - 4 Indian centers Treatment and study of ALL in India - 4 Indian centers Treatment and study of Burkitts Lymphoma in Africa - 4 centers in 3 countries (expanded access in Tanzania) Treatment and study of Burkitts Lymphoma in Africa - 4 centers in 3 countries (expanded access in Tanzania) Palliative care; provision and training – 4 countries Palliative care; provision and training – 4 countries Expansion of care for leukemia (Philippines) Expansion of care for leukemia (Philippines)

Projects in Planning Phase Treatment of locally advanced retinoblastoma (Philippines, Turkey) Treatment of locally advanced retinoblastoma (Philippines, Turkey) Treatment of breast cancer (with IAEA) Treatment of breast cancer (with IAEA) Cervical cancer screening and treatment Cervical cancer screening and treatment Palliative care in Nicaragua (PACT) Palliative care in Nicaragua (PACT) Cancer control in Cameroon Cancer control in Cameroon Cancer control in Uzbekistan Cancer control in Uzbekistan

DELHI CHENNAI (168) o DELHI (232) MUMBAI (652) Acute Lymphoblastic Leukemia ALL study: 1048 Patients

Improvement over time with MCP 841 at TMH

Research Projects PROJECTS INCTR Programs, Branches, Associate Members, Partners Disease Specific Strategy Groups Scientific Review Ethical Review Implementation

Strategy 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 Workshops Provide basic information on clinical trials in cancer prevention and treatment Provide basic information on clinical trials in cancer prevention and treatment Associated with training of data managers Associated with training of data managers Supported by pharmaceutical industry Supported by pharmaceutical industry Held in China and Brazil to date Held in China and Brazil to date

Educational Meetings Workshops and training courses Jordan, Iraqi Ped Onc Workshop, April 2004 Nurses Oncology Training, Cairo, October 2003 Includes courses in GCP

Expert 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

Strategies Will need to develop training courses in both clinical science (oncology) and infrastructure required for trials management, including CTOs Will need to develop training courses in both clinical science (oncology) and infrastructure required for trials management, including CTOs Accreditation of individuals and institutions would be valuable Accreditation of individuals and institutions would be valuable Continuing education essential Continuing education essential A system of monitoring will need to be put in place A system of monitoring will need to be put in place

Expanding Access Create centers in appropriate institutions that can participate in projects that encompass research, service provision and the simultaneous provision of training and education to provide a FOCUS Create centers in appropriate institutions that can participate in projects that encompass research, service provision and the simultaneous provision of training and education to provide a FOCUS Develop a plan for creating satellite centers such that KSD and research are expanded within the country in a coordinated fashion Develop a plan for creating satellite centers such that KSD and research are expanded within the country in a coordinated fashion Maximize in-country training; utilize where necessary training in established centers in other developing countries of similar SES Maximize in-country training; utilize where necessary training in established centers in other developing countries of similar SES

Maximizing IT Telesynergy or internet-based lectures, focused meetings and training courses Telesynergy or internet-based lectures, focused meetings and training courses Use of PORTAL for Staff Workspaces Use of PORTAL for Staff Workspaces Use of PORTAL for discussions, surveys & free contributions Use of PORTAL for discussions, surveys & free contributions

Communication Tools Newsletter: NETWORKNETWORK WorkspaceAdmin. Workspace Education SiteMembers ForumAnnual Meet. Workspace

Strategy for Sustainability In country training with hands-on experience: long term collaborative research projects with immediate benefits to patients In country training with hands-on experience: long term collaborative research projects with immediate benefits to patients –Clinical trials of locally relevant approaches to screening and treatment provide improved care as well as professional education –Development of training centers that will expand the workforce and increase access to care in the country or region Education and training built around projects Education and training built around projects –Training in scientific methodology: enhanced professional experience; independence Information collected provides a foundation on which to build future endeavors Information collected provides a foundation on which to build future endeavors

Evidence Based Cancer Control – Multiple Benefits INCTR is working with Cochrane Cancer Network and other partners to: INCTR is working with Cochrane Cancer Network and other partners to: –Catalogue available evidence from developing countries –Develop a training program for secondary review (and therefore, disease experts) –Create a data base of secondary reviews –Identify gaps in knowledge and promote clinical trials to fill them

Secondary Research Knowledge of existing literature is essential in order to decide which questions are worth answering (the art of science) Knowledge of existing literature is essential in order to decide which questions are worth answering (the art of science) Training in the evaluation of published research provides an understanding of the scientific method in a clinical context Training in the evaluation of published research provides an understanding of the scientific method in a clinical context Thus, an important part of education in the conduct of clinical trials and sustainability Thus, an important part of education in the conduct of clinical trials and sustainability

Summary and Conclusions Clinical trials essential in developing countries: Clinical trials essential in developing countries: –Outcomes of interventions may differ from those in affluent populations – new evidence base required –Best interventions may differ from rich countries because of toxicity, cost or limited access (expertise, materials) –Clinical trials can be a focus for building capacity, and can lead to immediate patient benefits while building a foundation of data on which to make further progress Collaboration between governments, corporations and NGOs (including academia) should be mutually beneficial and benefit patients everywhere Collaboration between governments, corporations and NGOs (including academia) should be mutually beneficial and benefit patients everywhere Scientific training is best done via hands-on training in both primary and secondary research Scientific training is best done via hands-on training in both primary and secondary research