Workshop on Clinical Trials Capacity in Low- and Middle...

Workshop on Clinical

Trials Capacity in Low- and

Middle-Income Countries:

Experiences, Lessons

Learned and Priorities for

Strengthening

MEETING REPORT

ALLEVIATING THE HEALTH CONSEQUENCES OF POVERTY BY ENHANCING PUBLIC-PRIVATE COLLABORATION

Workshop on Clinical Trials Capacity

in Low- and Middle-Income Countries:

Experiences, Lessons Learned

and Priorities for Strengthening

Report of a Meeting Organized by theInitiative on Public-Private Partnerships

for Health

Novotel Mount Meru Hotel

Arusha, Tanzania

15–16 November 2002

Workshop on Clinical Trials Capacity in Low- and Middle-Income Countries: Experiences, Lessons Learned and Priorities for Strengthening

© Initiative on Public-Private Partnerships for Health, Global Forum for Health ResearchPublished by The Initiative on Public-Private Partnerships for Health,Global Forum for Health Research, March 2004 ISBN 2-940286-17-5

The reproduction of this document is regulated in accordance with the provisions of Protocol 2 of theUniversal Copyright Convention. All rights are reserved by the Initiative on Public-Private Partnershipsfor Health, Global Forum for Health Research. The document may be freely reviewed and abstracted,with the usual acknowledgement of source, but not for sale or for use in conjunction with commercialpurposes. Requests for permission to reproduce or translate the report, in part or in full, should beaddressed to the Initiative on Public-Private Partnerships for Health where information on any transla-tions or reprints is centralized (see address below).

The named authors alone are responsible for the views expressed in this publication.

Some of the information contained in the paper may be based on interviews, studies, research, literaturereview, professional advice and/or opinion; some information is supplied by third party sources. Theauthor has used his/her best efforts to accurately interpret and report this information and to allow con-tributors to review/correct/add when possible but cannot guarantee that the original information as sup-plied by others is correct or complete, or that it was accurately portrayed. The author and IPPPH makeno representation regarding the completeness, accuracy, up-to-dateness, or adequacy of the informationor materials it contains.

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IPPPH SECRETARIAT

Roy Widdus, Project Manager

Armelle Armstrong, Communications Officer

Pamela Atiase, Administrative Assistant

Alessandra Botta, Information Research Specialist

Karin Holm, Senior Programme Officer

Contents

Acronyms and Abbreviations iv

1. Thematic Summary 11.1 Background 1

1.2 Overall ‘global’ planning to strengthen clinical trials capacity 1

1.3 Perspectives on clinical trials in East Africa 1

1.4 Clinical trials as a ‘gateway’ 2

1.5 Concerns regarding historical experience with clinical trials 2

1.6 Communications 2

1.7 Major needs in strengthening clinical trials capacity 3

1.8 Responsibilities of national governments 3

1.9 Responsibilities of research institutions 3

1.10 Sustainability of clinical trials capacity 3

1.11 Perspective of different ‘constituencies’ 4

1.12 Follow-up to the meeting 4

2. Meeting Report 5

2.1 Plenary session I 5

2.2 Plenary session II: Lessons learned 6

2.3 Plenary session III: Sustaining capacity 7

2.4 Plenary session IV: Conclusions of working groups 9

2.5 Plenary session V: Perspectives on coordinating support to

clinical trials capacity strengthening 9

2.6 Plenary Session VI: Next steps? 11

2.7 Closure of meeting 12

Annex 1 Agenda 13

Annex 2 List of participants 15

Annex 3 Building a platform for clinical trials in Africa (Summary) 20

Annex 4 Summary of survey of lessons learned 22

Annex 5 List of participants in working groups 23

Annex 6 Topics assigned to working groups 24

Annex 7a Report of the working group on overall management 25

Annex 7b Report of the working group on Good Clinical Practice (GCP)

and quality control 27

Annex 7c Report of the working group on community relations and

engagement 28

Annex 8 Criteria for assessing sites for clinical trials 30

Annex 9 Presentations and other documents 32

INITIATIVE ON PUBLIC-PRIVATE PARTNERSHIPS FOR HEALTH iv

AFHR African Forum for Health ResearchAMANET African Malaria Network TrustAMVTN African Malaria Vaccine Testing NetworkARV AntiretroviralsCRO Contract Research OrganizationEDCTP European and Developing Countries Clinical Trials Partnership (European Union)EMEA European Medicines Evaluation AgencyFDA Food and Drug Administration (USA)FIC Fogarty International Center, NIH (USA)GATBDD Global Alliance for Tuberculosis Drug DevelopmentGCP Good Clinical PracticeGLP Good Laboratory PracticeGMP Good Manufacturing PracticeGSK GlaxoSmithKlineHIV/AIDS Human Immunodeficiency Virus/Acquired Immunodeficiency SyndromeHIV/AVTN HIV/AIDS Vaccine Trial NetworkHRP Special Programme of Research, Development and Research Training in Human

Reproduction (WHO)IAVI International AIDS Vaccine InitiativeICAR International Centers for AIDS ResearchICDDR International Centre for Diarrhoeal Disease Research (Bangladesh) ICH International Conference on Harmonisation of Technical Requirements for

Registration of Pharmaceuticals for Human UseIEC Institutional Ethics CommitteeINCLEN International Clinical Epidemiology NetworkINDEPTH International Network of Field Sites with Continuous Demographic Evaluation of

Populations and Their Health in Developing CountriesIPM International Partnership for MicrobicidesIPPPH Initiative on Public-Private Partnerships for HealthIRB Institutional Review BoardIUATLD International Union Against Tuberculosis and Lung Diseases (France)IVI International Vaccine InstituteJCRC Joint Clinical Research Center (Uganda)KEMRI Kenya Medical Research Institute LMICs Low- and middle-income countriesMTCT Mother-to-child transmissionMMV Medicines for Malaria VentureMVI Malaria Vaccine InitiativeNGOs Nongovernmental organizationsNIAID National Institute of Allergy and Infectious Diseases (USA)NIH National Institutes of Health (USA)NIMR National Institute for Medical Research (Tanzania)NIPRD National Institute for Pharmaceutical Research (Nigeria)PATH Program for Appropriate TechnologyPAVE Preparation for AIDS/HIV Vaccine EvaluationsR&D Research and developmentSIDA/SAREC Swedish International Development Agency/Research BranchSOP Standard Operating ProcedureSTI Sexually transmitted infectionTB TuberculosisTDR Special Programme for Research and Training in Tropical Diseases (WHO)USAID United States Agency for International Development WHO World Health Organization

Acronyms and Abbreviations

1.1 Background

In November 2002, the Global Forum for HealthResearch held its sixth annual meeting, Forum 6,

in Arusha, Tanzania. During that meeting and inassociation with the Global Forum, the Initiativeon Public-Private Partnerships for Health (IPPPH)organized a workshop entitled Clinical trialscapacity in low- and middle-income countries:Experiences, lessons learned and priorities forstrengthening1 on 15–16 November 2002.IPPPH decided to hold the workshop because ofconcern that the current capacity to conductclinical trials of products for health problems inlow- and middle-income countries (LMICs) wouldbe insufficient over the next 10 to 20 years.Clinical trials for products to deal with the so-called neglected diseases cause particular concern,given the increased attention and new fundsdirected at them, and the advent of a number ofpublic-private partnerships to develop them.

The meeting brought together 77 individualsfrom 24 countries. The participants reflected thewide range of groups that associate to implementand support clinical trials: researchers from bothdeveloping and developed countries who areimplementing trials in LMICs; public healthpolicy-makers; community relations specialists;national health research institutes inindustrialized and developing countries; disease-oriented trials networks; pharmaceutical industryrepresentatives; foundations; public-privatepartnerships for product development; andbilateral agencies.

The meeting sought to identify and concentrateon cross-cutting needs and themes relevant to allclinical research and trials, whether for productsneeded in health interventions (drugs, vaccines,contraceptives, diagnostics, etc.) or for thedisease or health problems addressed.

This summary presents an overview ofdiscussions and conclusions, organized by theme.A more detailed record of discussions can befound in the meeting record, which is organizedby agenda session.

1.2 Overall ‘global’ planning tostrengthen clinical trials capacity

Participants first considered what is known aboutthe current capacity of certain LMICs to conductclinical trials and how this related to planning forfuture needs, with special emphasis on sub-Saharan Africa. It emerged that while isolatedefforts have been made to assess capacity andfuture demand (for example, by national healthinstitutes (NIH) in the United States and theInternational AIDS Vaccine Initiative (IAVI) onHIV/AIDS; the European and DevelopingCountries Clinical Trials Partnership (EDCTP)on HIV/AIDS, tuberculosis and malaria; and theAfrican Malaria Network Trust (AMANET),formerly known as the African Malaria VaccineTesting Network), there were no consistentcriteria for assessing current trials capacity orfuture needs and no organization that maintainedan overview on which to base coordinated effortsto strengthen capacities to match future needs.Participants cautioned that attempting to predictfuture needs was always subject to scientificuncertainty but that it could and should beattempted.

Given that strengthening sites for clinical trials isexpensive, it was suggested that investmentsshould focus on a limited number of sites, whichwould hopefully be ‘multifunctional’, acrossdiseases and product categories. This means,however, that not all aspiring institutions couldexpect major support.

1.3 Perspectives on clinical trials inEast Africa

Dr Ebi Kimanani reported on a survey ofattitudes towards, and capacities for involvement

1. Thematic Summary

WORKSHOP ON CLINICAL TRIALS CAPACITY IN LOW- AND MIDDLE-INCOME COUNTRIES 1

1 Such as IAVI, Medicines for Malaria Venture (MMV),Global Alliance for Tuberculosis Drug Development(GATBDD), Malaria Vaccine Initiative (MVI),International Partnership for Microbicides (IPM) andothers.

INITIATIVE ON PUBLIC-PRIVATE PARTNERSHIPS FOR HEALTH 2

in, clinical trials in East Africa. A number offactors constrained capacity, including access toequipment, understanding of Good ClinicalPractice (GCP), absence of ethical review capacity,and communications, especially in rural areas.However, the ‘good news’ was that despite somenegative experiences, there is still a strong desireto engage in clinical trials on locally relevantproducts, even where these had been developedoutside the region.

1.4 Clinical trials as a ‘gateway’

The concept of clinical trials (for efficacy) as a‘gateway’ between research and use of products inpublic health was widely recognized amongmeeting participants.

Clinical trials may be viewed as an exercise aroundwhich organizations from many different‘constituencies’ collaborate but to which theybring different motivations, contributions andlevels of resources (hence greater or less ‘power’)and have different aspirations and expectations.These constituencies include: researchers,clinicians and institutions in developing anddeveloped countries; public health ‘practitioners’;various funders, including national health researchagencies and foundations; development assistanceagencies; commercial pharmaceutical companies;members or representatives of the community inwhich the trial is undertaken; and the participantsin the trial themselves. Each constituency bringsits own ‘culture’ and expectations to thecollaboration. Problems arise, however, as oftennot enough care has been taken to reachagreement on widely acceptable outcomes. This,according to the meeting participants, may helpto explain difficulties, frustrations anddisappointments that often accompany clinicaltrials and strengthening of the capacity to conductthem.

1.5 Concerns regarding historical

experience with clinical trials

Problems that may occur in conducting clinicaltrials in LMICs can be grouped in threecategories although these may overlap andcompound:

• Difficulties arising from inadequateplanning, including insufficient input fromLMIC investigators into products orinterventions to be studied or into trialdesign; inadequate resources for pre-trial

site characterization; and inadequateengagement of local communities duringpreparations for trials.

• Frustrations in executing trials, includingunderestimation of the time needed toinstal equipment and train staff; lack ofclarity about essential GCP norms; absenceof local or national ethical reviewcommittees and/or the need for multipleInstitutional Review Board (IRB) ethicalclearances; defining the purpose and natureof informed consent; and inadequatetraining and involvement of LMICinvestigators in data management andstatistical analysis.

• Disappointments in post-trial outcomes,including lack of access to productssuccessfully tested; inadequate preparationfor retaining site capacities, e.g., throughpreparing ‘local’ investigators to competefor research funds on projects relating toregional or national health problems; lackof career structures for LMIC clinical trialsspecialists, necessitating part-time privatepractice or emigration.

1.6 Communications

The need for careful attention to the multipleaspects of communications around clinical trialswas a theme that arose repeatedly in theworkshop.

• For clinical trials to succeed, partners fromthe different constituencies need to trusteach other, understand the use ofterminology and have clear expectations.Building this trust and understanding maytake considerable time, and longer thatsome investigators from developedcountries anticipate.

• Discussing post-trial expectations (bydifferent constituencies) was generally feltto be a useful component of trial planning.

• Implementation of the trial itself may befacilitated by explicit written agreement onroles, responsibilities, milestones anddeadlines for all major players.

• Early and frequent communication with allrelevant regulatory authorities is essential.

• Frequent communications betweenimplementers and sponsor(s) of trials


(especially if the latter is a commercialpharmaceutical company) are also veryimportant.

• Investigators in rural areas need to be ableto communicate both with inwardtransmission of trial and patientinformation and feedback to the rest of thetrial team. New technologies offeredpossibilities in some of these areas.

1.7 Major needs in strengtheningclinical trials capacity

Major needs highlighted by the working groupsincluded:

• Overall management:

–— Leadership and management training.–— Training local researchers for principal

investigator positions. –— Strengthening financial accounting in

institutions in LMICs. –— Possible creation of specialized training

courses in academic institutions onclinical trials design and execution.

• Good Clinical Practice and qualitycontrol:

–— Define and create a broadunderstanding of the GCP componentsthat are essential for regulatory approvalof products subject to trials in LMICs.

–— More training in GCP adherence. –— Creation of functioning national and

institutional ethical review committeesand training for their members.

• Community relations and engagement:

–— Wider understanding that strategies toengage the community are an integralpart of the research and development(R&D) process.

–— Development of strategies that betterdefine the ‘community’, which willdiffer according to the phases of trialsbeing carried out.

–— Implementing ‘social contracts’ withcommunities, to define expectations and‘deliverables’.

–— Define and differentiate informedconsent and informed decision-making.

–— Inclusion of community ‘preparation’strategies as part of essentialexpenditures.

1.8 Responsibilities of nationalgovernments

LMIC national governments can create anenvironment conducive to strengthening clinicaltrials capacity by:

• Ensuring that national bioethical reviewcommittees are actually functioning in atimely fashion.

• Ensuring that national regulatory functionsfor pharmaceuticals are strengthened.

• Establishing national policies encouraginghealth research and contributing to themfinancially, even in modest amounts.

• Identifying national health researchpriorities.

1.9 Responsibilities of researchinstitutions

Research institutions can create an environmentthat encourages the strengthening of clinical trialscapacity by:

• Ensuring functioning institutionalbioethical review committees.

• Establishing adequate, audited financialmanagement capacities.

1.10 Sustainability of clinical trialscapacity

Participants repeatedly noted the waste ofresources and frustration caused by inadequateplanning for sustaining capacities developedduring trials. However, they recognized thatfunders would not support maintenance ofcapacity that was not being put to productiveends.

A number of approaches to sustaining capacitywere proposed:

• Support for trials could incorporatecomponents to train junior/LMICinvestigators in trial design and proposalwriting (including budget preparation andmanagement). This would help them tocompete for funds offered by externalsources such as the World HealthOrganization (WHO) Special Programmefor Research and Training in TropicalDiseases (TDR) and its Special Programmeof Research, Development and ResearchTraining in Human Reproduction (HRP).This was widely supported as a means to


strengthen local clinical research andclinical trials capacity and to encouragetesting of interventions identified asrelevant to local health problems.

• Exploring the possibility of establishingpharmaco-vigilance studies and systems,subsequent to efficacy trials. (Someparticipants stressed that such efforts wereethically necessary before wide applicationof successful products.)

• Encouraging even modest support fromLMIC governments for maintainingcapacity, possibly in the form of smallcompetitive grants on local healthproblems.

1.11 Perspective of different‘constituencies’

Participants from various ‘constituencies’represented at the meeting provided the generalperspectives of their institutions:

• Although participants recognized thatmuch needs to be done to strengthenclinical trials capacity in LMICs, the majorfunders have particular missions, mandatesor business goals. Therefore, while ageneralized strengthening effort might bedesirable and efficient, in practice it mightbe achievable in some areas, but would bedifficult across the whole array of needs.

• Planning and capacity strengtheningappeared to be most effective when builtaround discrete projects. Particularproducts passing through the clinicalresearch and clinical trials pipeline providedthe best opportunity for the design oftargeted activities.

• The challenge is how to match generalcontributions to strengthening clinical trialscapacity (e.g., general training in GCP,bioethics, management, data management,etc.) to the efforts needed on specificproducts or diseases. Some overarchingplanning seems feasible and desirable, butno institution appears at present to havethe full information (or inclination) neededto do this.

It was agreed that input should be sought from arepresentative sample of francophone countries,since their representation in the meeting wasnumerically low.

1.12 Follow-up to the meeting

In a brainstorming session at the close of themeeting, two principal suggestions emerged:

• In the course of the discussions, manyrelevant (but relatively unknown)information sources or discrete assessmentsrelating to clinical trials capacity in LMICshad been identified. An attempt should bemade to produce and disseminate acompendium of these sources with contactinformation.

• Preparation of a consensus document on‘Good Practices in the Sponsorship andImplementation of Clinical Trials in Low-and Middle-Income Countries’ should bediscussed among relevant, interestedparties.


2.1 Plenary session I

Chair: Dr Wenceslas KilamaCo-chair: Dr Roy Widdus

Drs Wenceslas Kilama and Roy Widduswelcomed the participants and explained that

the meeting aimed to identify areas of need andpotential collaboration for clinical trialinfrastructure in low- and middle-incomecountries.

In order to assess capacity, Dr Widdus proposedto use a matrix approach based on threedimensions:

• The ‘product pipeline’ and what trials willbe needed in the near future.

• The geographical locations and potentialsites.

• What strengthening is needed based oncurrent capacity?

The areas to focus on should also be clarified, byidentifying common needs among all clinicaltrials.

Dr Ebi Kimanani presented an assessment ofexisting clinical trial capacity, particularly in Africa,based on a survey she conducted in 28 sites in 16African countries, including university trainingcentres, medical practitioners and someresearchers. The most common specialistsinvolved in trials were public health andprevention professionals and paediatricians. Themost common subjects were HIV, tuberculosis(TB), malaria, paediatric diseases and nutrition.Some 38% of personnel have experience withPhases I to IV studies, and only 9% mentionedhaving preclinical experience.

The survey identified the following issues:• Medical professionals from rural areas are

often isolated.

• Investigation selection criteria are nottransparent.

• Facilities and transportation are inadequate.

• There is a lack of political will and lack offunding.

Dr Kimanani concluded that guidelines andreview boards need to be put in place and thatregulatory and ethics procedures need to beagreed upon and more widely understood.

Dr Rodney Hoff presented an overview ofinternational health programmes organized by theUnited States’ National Institute of Allergy andInfectious Diseases (NIAID) focusing on tropicaldiseases and HIV/AIDS (available on request, seeannex 9). The assessment of needs and clinicaltrial sites is disease burden-oriented. Theapproach used is testing interventions in aindividual site or using an existing diseasenetwork. A competitive peer review drives the siteselection based on trials requirements.

Dr Hoff provided an example of how this wasachieved in the past with HIV prevention: theUnited States’ National Institutes of Health(NIH) and International Centers for AIDSResearch (ICAR) began seroprevalence studies in1988; PAVE (Preparation for AIDS/HIV VaccineEvaluations) conducted cohort studies (1991);HIVNET (an NIH/NIAID trials network)carried out population-based laboratory studies(1993); and two networks for clinical trials wereset up in 1999. The network was established,investigators were requested to propose studies(sexually transmitted infections (STIs),antiretrovirals, microbicides, etc.) and second siteswere asked to demonstrate capacity to enrol andsubmit credentials.

Also presented was the concept of the Europeanand Developing Countries Clinical TrialsPartnership (EDCTP) as a platform for fundingtrials in sub-Saharan Africa (available on request,see annex 9). The programme aims at investing inthe long-term sustainability and rational use oftrial sites and anticipates ten trials in the next five

2. Meeting Report


years. The programme has classified fourcategories of trial sites:

• Those that are already capable ofconducting major studies and that complywith the regulatory requirements of theInternational Conference onHarmonisation of Technical Requirementsfor Registration of Pharmaceuticals forHuman Use (ICH).

• Those that could rapidly reach ICHrequirements.

• Those that need significant capacitybuilding to reach ICH requirements.

• Those that are unlikely to meet regulatorystandards in the foreseeable future.

EDCTP also plans to implement a programme onleadership training, to begin in 2003.

Discussion

Participants noted that trials should becategorized according to the nature of theirintervention, for example:

• Epidemiology and behaviour (interventionof education, advocacy, questionnaires).

• Clinical epidemiology (intervention basedon readouts from biological samples(blood) taken from participants).

• Vaccine trials (invasive administration of acandidate product to the participants andlong follow-up).

• Drug trials where more or less invasivetreatments are administered to the patientsand in general need relatively limited follow-up for efficacy, safety and adverse events.

During the discussion a number of issues andquestions were raised:

• Many researchers working part-time onclinical trials seem to be less effective thanfull-time staff. What can be done?

• Is the research agenda driven by externaldonors or by the indigenous nationalresearch community? Products developedin the ‘North’ are usually tested in the‘South’.

• How to raise standards?

• What could be the role of industry?

• Would larger investments in fewer projectsbe more effective?

2.2 Plenary session II: Lessons learned


Dr Lise Riopel presented the results of a survey oflessons that participants had learned from theirexperience with clinical trials in LMICs (see alsoannex 4). The issues identified were summarized as follows:

• Training in GCP and study management.

• Improving local communication withsponsors, particularly pharmaceuticalcompanies.

• Sustaining resources beyond the trialperiod.

• Underestimation of funding required forclinical trials.

• Improving ethics review which is often notunderstood.

• Improving communication among allparties in results analysis and publication.

Dr Osman Sankoh (INDEPTH) reported on acapacity-building meeting (May 2002). Themeeting discussed the EDCTP assessmentdocument which aimed at creating an enablingenvironment for clinical trials in developingcountries, e.g., strong rationale for trials, solidinfrastructure, qualified skilled personnel.However, the meeting concluded that there was:

• Insufficient medical research andequipment.

• Deficient clinical design.

• Low national interest and support.

• Lack of clear applicable guidelines.

• Lack of control and regulatoryharmonization.

• Little interaction with industry.

To improve capacity, activities should focus oncollaboration procedures, the assessment of trialsites and a greater participation of local scientists.Other issues discussed included:

• How to improve facilities, training (whoand how) and management.

• How to halt the ‘brain drain’.

• Factors influencing costs (number of trials,requirements, complementarity, etc.).


• Supporting local review systems andfollow-up in order to develop good,locally-originated studies.

Discussion

Participants agreed that, before beginning trials in acertain locality, the availability of products to thatcommunity once the trials have finished must beensured. Also, local manufacturing capacity or atleast supply and cost issues need to be consideredwhen discussing long-term sustainability of drugsand vaccine supply. Participants asked whethersome sponsors held product trials in countrieswhere they did not plan to register them, andpointed out that, ethically, the products should bemade available wherever successfully tested.

Participants also brought up the following issuesduring the discussion:

• In low-income countries, trials are usuallypublic-private partnerships. Negotiationsfor trials take account of local interests.Many neglected diseases have beenaddressed in this way.

• Although quality standards are universal,future product supply should be addressedon a case-by-case basis.

• Documentation, audits and issuesconcerning placebos should be taken intoaccount.

• Before each trial, the risk/benefit ratio forthe trial population has to be considered.

• Some investigators are overwhelmed andconfused by the multitude and variety ofguidelines. One solution would be to buildon existing guidelines to compile allrelevant major guidance. Simplification ispreferable to creating regional, local orspecific guidelines, which would be time-consuming and complex.

Dr Giorgio Roscigno added that it is veryimportant to have standard operating procedures(SOP) that are fully understood locally. GCP hasbeen implemented successfully in Africa indifferent trials (microbicides, HIV vaccines, etc.).However, few sites currently meet GCP standards.A continuous flow of resources is key to keepingtrial sites up to good standards but resources maylapse after trials are completed. Technologytransfer is a critical issue, and a challenge. Sitemaintenance needs to be considered. MaryNewton (Roche) mentioned that clinical trial

capacity compatible with international standardsneeds government involvement, and that there isnow good support in South Africa.

Dr Luis Jodar (IVI) mentioned that the productprofile should be considered together with localscientists and government, taking into accountlocal epidemiological, logistical and programmaticissues. So-called ‘learning by doing’ waschallenged in the discussion, as credibility needsto exist before funding is given. However,establishing credibility without prior experience ofactual trials is a challenge.

Working group sessions

Working groups were set up to enable participantsto feed maximum information into thedevelopment of priorities. The topics addressed byeach of the working groups were:

• Overall management

• Good Clinical Practice and quality control

• Community relations and engagement.

Participants to each working group and the topicsassigned to them are shown in annexes 5 and 6respectively.

Reports from the working groups are taken intoaccount in the thematic summary and areincluded as annexes 7a, 7b and 7c.

2.3 Plenary session III: Sustainingcapacity

Chair: Dr Wenceslas KilamaCo-chair: Dr Uford Inyang

Dr Wenceslas Kilama introduced the generalconcerns over sustaining capacity based onobservations in Africa, particularly in East Africanmalaria interventions. Personnel are assembled fora trial (particularly Phase III), investments intraining have been made, the community’sinterest is mobilized, but often there is nothought as to what will happen once a trial is over.An issue is long-term efficiency, i.e., not losingthe value of investments already made, rather thansustaining capacity as an end in itself.

The roles of institutional and government

policies in sustaining capacity

Dr Uford Inyang (Nigeria) identified additionalissues not only in sustaining capacity onceestablished but also in using existing capacityeffectively, based on his own institution’s


experience and that of others. In Nigeria, there aremany specialist teaching institutions in health andspecialist hospitals, plus a national drug regulatoryagency. Guidelines and – in theory – an ethicalreview committee exist. However, the system’soperations are not optimal as enforcement is weakand the ethical review committee has essentiallylapsed. Variations from recommended practice aregranted if sponsors insist on their own protocols orbypass usual procedures. Hence, monitoringcompliance with standards is as important as theexistence of policies. He emphasized theimportance of national governments andimplementing institutions being committed notonly to create policies to guide trials but also toensure that the mechanisms actually function.

Participants raised a number of issues:• By ‘sustaining capacity’, participants from

LMICs often meant creating the conditionswhere the personnel engaged in the trialwere able to continue investigating pertinenthealth problems. Simply sustaining capacityto await the next ‘big trial’ was unrealisticand not an end in itself.

• Mid- and junior-level researchers involvedin larger trials on externally developedproducts/interventions should beencouraged and empowered to identify andaddress research questions pertinent to‘local’ major health problems.

• To continue to apply research capacityassembled during a large trial to localproblems required building certaincomponents, largely directed towards mid-and junior-level investigators, into the initialtrial plan. These included provision for:

–— Training in study design, grant writing,and creation and management ofresearch budgets.

–— Training in leadership and managementskills, so that ‘local’ researchers canbecome the principal investigators onfuture new projects.

–— Giving mid- and junior-level researchersthe opportunity to travel and establishtheir own contacts for futurecollaborative projects.

• Budgetary provision in the initial trial forthese types of activities need not be largebut should be explicit. Such provisionscould be linked to information about

opportunities for initial/small grants.Other sources were also available, e.g.,TDR proposal writing workshops.

• It was acknowledged that, at present,funding for ‘developing country driven’research is meagre; development agenciesshould increase its availability and broadeneligibility (from known, senior LMICscientists to emerging ones).

• Few suggestions emerged, however,regarding creating career paths andmaintaining skills among nurses andcommunity health workers who wererecruited and trained for large trials.Shortage of funds for careers in healthresearch institutions was one of the maincauses of the ‘brain drain’.

Participants acknowledged that trial sites werechosen for a variety of reasons. Some were selectedor deliberately established for a long-term (20 yearsor more) research programme, others wereintended simply to test one product/intervention.However, in all cases, the sponsor could build inactivities that would help strengthen and sustain‘local’ capacity. Specifying desired outcomes at theoutset of the collaboration would also reducemisunderstanding, unmet expectations anddisappointments.

Sponsors (research funders, product developers,development agencies, health service providers,etc.) would be better able to target their supportinterventions if they discussed the trial’s desiredoutcomes in early negotiations.

Participants also identified good practice in largeintervention trials, which were less directly relatedto sustaining capacity, especially when they wereheld in developing countries but largely driven bysponsors from the industrialized world:

• Collaborators should agree in advance on aspecific plan for analysis and disseminationof results, including publication, authorshipand communication to the community.

• In long-term relationships, explicit plansshould be made to correct what are likelyto be initial disparities in capacity (and thusperceived power and rights of control).

• Linking research projects as far as possibleto ongoing provision of health services willultimately improve their reception andrelevance.


• Capacity-building aspects of large trials wererarely documented and various differentnational approaches to choosing trial sitesexist (e.g., China’s government certifies siteswhich sponsors must then use). Case studiesdocumenting and comparing approachesand experience were recommended.

• Many site assessment, technical andleadership training, and other capacity-strengthening operations exist, such asAMANET and African Forum for HealthResearch (AFHR). However, they are notalways linked or widely known. Aninformation resource is needed to avoidduplication of effort and to facilitate accessto the extensive work already done.

2.4 Plenary session IV: Conclusions ofworking groups

Chair: Dr Wenceslas KilamaCo-chair: Dr Gerald Keusch

Participants in the three working groups are listedin annex 5.

Reports from these groups are included asannexes 7a, 7b and 7c. Discussion of the workinggroups’ conclusions was incorporated into thefinal plenary session (V).

Conclusions from the working groups arereflected in the thematic summary.

2.5 Plenary session V: Perspectives oncoordinating support to clinicaltrials capacity strengthening

Chair: Dr Wenceslas KilamaCo-chair: Dr Gerald Keusch

The IPPPH Secretariat asked the followingquestions:

• Is more coordination and more financialsupport needed?

• In what ways could more coordination beachieved?

All participants contributed to the discussion, andgenerally acknowledged that the strengthening ofclinical trials capacity in LMICs (particularlyAfrica) had been a by-product of specific trials,not a primary goal at the outset.

Various participants, e.g., industry and NIAID(USA), indicated that they engaged in clinical trials

mainly as a result of their commercial or scientificresearch mission to develop new products. Theiranticipation of needs for trial sites was usually veryproduct specific. This product orientation drovethe preparation process for clinical trials, includingstrengthening where necessary. New engagementfrom NIH intramural programmes was allowingfor a longer-term relationship with sites indeveloping countries and hence possibly morestrengthening for conducting clinical trials.

Other participants indicated a broader missionrelated to clinical trials capacity (such as the USNIH Fogarty International Center (FIC), whichconducted training in various clinical trial-relateddisciplines) or overall research in healthproblems of developing countries (e.g.,Wellcome Trust, which supported researchcentres). The latter necessitated a substantialinvestment in community relations especially forpopulation-based research projects.

Participants’ comments illustrated the diversenature of actions and actors necessary for buildingboth clinical trial and general research capacity,particularly in Africa.

The Sequella Global Tuberculosis VaccineFoundation (now named the Aeras GlobalTuberculosis Vaccine Foundation) identifiedneeds and ensured that sites for TB vaccine trialswere prepared adequately (backgroundinformation is available, see annex 9). They areworking towards supporting developing groupsand funding actual candidate product testing.

The Global Alliance for Tuberculosis DrugDevelopment (GATBDD) had also identified acritical need for clinical testing (Phase III) of newdrugs. It created, in collaboration with theInternational Union Against Tuberculosis andLung Diseases (IUATLD), a research network inLMICs, organized from South Africa, to engageand strengthen potential clinical trials sites,especially in laboratory skills. This preparation wasnecessary as GATBDD aimed to have sevencandidates in some phase of clinical testing by2005. GATBDD representatives stressed theimportance of parallel efforts to strengthennational regulatory capacity.

The Program for Appropriate Technology’s(PATH) Malaria Vaccine Initiative was laying outexpectations for clinical trials of candidateproducts as a preliminary step to identifyingpotential trial sites. A challenge was striking abalance between the desirability of general clinical


trial capacity development and the needs for theirmore targeted goal of product development.

Other interventions included:• The recently-created African AIDS Vaccine

Initiative is assessing trial capacity andwould publish a report on its work (DrJosé Esparza, WHO).

• Some sites in Africa already hadconsiderable experience in therapeutic andpreventive intervention trials. Projects suchas NIAID’s HIVNET/AIDS Vaccine TrialNetwork (AVTN) could create newcapacity, train a new generation ofresearchers and strengthen bioethicalreview and community engagementapproaches (Dr Danstan Bagenda).

• A number of ‘donor’ groups could assistwith clinical trials capacity strengthening(Dr Gerald Keusch, NIH/FIC).

• Specific ventures, such as the EDCTP, mighthelp these groups to move forward in acohesive fashion (Dr Mike Hollingdale).

• Some bilateral aid donors, such as theresearch branch of the Swedish InternationalDevelopment Agency (SIDA/SAREC),pointed out that their support strategieswere more oriented towards long-termsupport of institutions, not earmarked tospecific projects like clinical trials.

• IAVI was committed to engaging developingcountry researchers in their productdevelopment ‘partnerships’ from the earlieststages. Nine Phase I trials were in progressincluding one in Uganda and Kenya and 16potential trial sites in seven countries hadbeen evaluated (Dr Nzeera Ketter).

• As a donor, USAID’s country support waschannelled through global funding (moreresearch oriented) and local countrymissions. Documenting successes wouldhelp demonstrate that research supporteddevelopment (Dr Ruth Frischer).

• The UK Medical Research Council Unit’sexperience in the Gambia showed thatbuilding capacity was a difficult and fragileprocess: specific individual trials would notnecessarily result in sustainable capacity.The concept of ‘passing the baton’between successive trials and strengtheningcare provision should be explored (Prof.Keith McAdam).

• Merck was moving more products intoclinical trials outside industrializedcountries as more products such as newHIV/AIDS drugs needed testing. Thecompany was conducting trials in 58countries (up from 27 countries a few yearsbefore). The increase mainly concernedcountries in Eastern Europe, Asia and LatinAmerica, although Merck felt a discussionof needs in Africa was useful, to establishcontacts for a network of local expertise. Inassessing trials sites, the company evaluatedinfrastructure and disease prevalence, butthe roles of clinical monitor/studycoordinator and principal investigator wereconsidered critical among personnel needs(Dr Jacobo Sabbaj).

Participants felt site strengthening was probablybest done on a case-by-case basis, but some cross-cutting needs were evident. These needs, whichcould be supported by governments andmultilateral institutions to raise capacity andstandards in general, included training, possiblywith industry collaboration, to extendunderstanding of and capacity to implement GCPfor trials, and to establish stronger capacity inregulatory structures.

In discussing this topic, a number of points wereraised:

• While industry in general would welcomepublic sector initiatives along these lines,care should be taken to avoid bureaucraticdelays. Industry, being sensitive totimelines, tended to avoid countries withcumbersome decision-making procedures(Dr Jacobo Sabbaj).

• Some companies have a large portfolio ofcandidate products for ‘neglected’ diseasesand testing in disease-endemic countrieswas the only feasible option.GlaxoSmithKline (GSK) was collaboratingwith a number of not-for-profit‘partnerships’ that facilitated testing andenabled the company to be more active inthese less lucrative fields where the needwas mostly in developing countries, e.g.,malaria and rotavirus vaccines (Dr JoachimHombach).

• At many potential sites, the capacity toconduct adequate ethical review should bestrengthened. Routine health-care servicesalso need to be strengthened and/orfunded, so that existing and emerging


products could be more fully utilized (DrJoachim Hombach).

• GSK was interested in trial sites in sub-Saharan Africa, but needed guidance onexisting and prospective sites and theircapabilities (Dr Opokua Ofori-Anyinam).

• Merck agreed that clinical trial capacity inAfrica should be addressed – not only therange of issues mentioned by Dr Sabbaj, butalso the question of availability of theproducts for general patient care after asuccessful clinical trial (Dr Henrietta Ukwu).

African participants noted some of their specificconcerns:

• Africa as a whole lacked a sufficient numberof centres of research excellence andfunding for specific activities needed to bepart of other broad-based activities (Prof.Bartholomew Akanmori).

• A longer-term dimension was needed,which AFHR might be able to provide (DrEbi Kimanani).

• The Central African region in particularwas in need of more institutionalstrengthening but was often neglected interms of targeted support from donors orprogrammes (Prof. Rose Leke).

• Action was needed on many fronts inNigeria for, although it had a number ofinstitutions with reasonable capabilities, theenvironment was difficult as the centralgovernment needed to fulfil certainresponsibilities (in regulation and ethicaloversight) (Dr Uford Inyang).

• Traditional links, often from colonialpowers, dominated patterns of collaborationand support for research and institutionaldevelopment. The pattern of French supportfor Senegal, German support forGabon/Cameroon, British support for EastAfrica and the Gambia, and US engagementwith South Africa supported this contention.In Africa, AMANET/AMVTN hadidentified 30 institutions with some researchcapacity; ten of them would perhapsconduct trials because of the links citedabove. Hence, about 20 institutions neededsupport and partnering to fulfil theirpromise (Dr Wenceslas Kilama).

• Establishing strong national researchcapacity was important as it played a major

role in driving national health policygenerally. However, francophoneinstitutions and networks were often notwell integrated in discussions on Africa’soverall needs in research and health. DrOumar Gaye and a number of otherparticipants emphasized the need toincorporate francophone input in activitiesfollowing the workshop.

Concern was expressed by a number of participantsfrom Africa that in both clinical trials and supportfor other research, the ‘local’ voice in setting healthresearch priorities was weak or non-existent. Onesuggestion for improving this situation was toinclude training in proposal writing and budgetdevelopment for junior and mid-level staff in trialsdesign, so that they could propose follow-upresearch on local priorities. Expansion of funds forsuch locally-initiated research, e.g., via WHO’sTDR and HRP, etc., would be essential. Someparticipants felt that institutions or governmentsshould decline approval for trials that did notaddress local health needs.

Matching support to priority needs

Some participants supported the need for bettercoordinating support from different donors atparticular sites and possibly doing this within alarger assessment of needs and opportunities.However, a majority of participants felt that thebest course of action was an approach based oncoordination of site strengthening aroundidentified needs for testing particular products.

Common ground existed to the extent that mostparticipants acknowledged that a wealth ofinformation existed on different facets of thetopics discussed, and that a useful and necessaryfirst step was to inventory this and make it morereadily accessible.

2.6 Plenary session VI: Next steps?


The IPPPH Secretariat asked what was desirablein the aftermath of the meeting (beyond ameeting report) and who should do it.Participants noted that the discussions hadcovered a wide range of topics and identifiedmany steps that would ameliorate some of theproblems. In almost every area where a need hadbeen identified, some information existed thatwould at least in part resolve the problem.


However, often many of those conducting trialsor strengthening capacity were unaware that suchresources existed and, given the lack ofmechanisms or clearing houses, could not find outhow to access them.

Selected examples of existing resources not widelyrecognized or accessible from a centralizedlocation included:

Conduct of clinical trials

• International Conference onHarmonization Guidelines on GoodClinical Practice (GCP).

• Guides to interpretation/implementationof GCP, from UNDP/World Bank/WHO(TDR) and the SCRIP Journal.

• Training courses in clinical trials conductand GCP implementation, e.g., TDR.

Assessment tools for clinical trials capacity

• AMANET checklist for site capacityassessment.

• EDCTP checklist for capacity assessment.

• African AIDS Vaccine Initiative assessmentof site capacity (in progress).

• Covance, a contract research organizationassessment tool for initial evaluation ofpotential trial sites (see annex 8).

Inventories of assessment sites

• AMANET assessment of sites for malariatrials in Africa.

• INDEPTH site assessments forepidemiological studies.

• IAVI site assessments for HIV vaccinetrials.

• NIAID/HIVNET site assessments for HIVprevention trials.

• IUATLD trials site network.

Ethical review processes

• A number of guides, other resources ortraining opportunities were mentioned,including those operated by NIH/FIC andWHO programmes.

• AFHR was in the process of analysingbioethical review systems and capacity inAfrica.

Participants generally acknowledged that a rangeof cross-cutting capacities, necessary forconducting all clinical trials, did exist. These

included, for example: management and financialexpertise, bioethical review and statistical analyses.However, comments revealed a wide diversity ofmandates and decision-making processes that ledto financial support for particular clinical trials.While participants agreed that donor support tothese capacities should be better coordinated, itwas clear from such comments that achieving amore cohesive approach would be neither easy toachieve nor a high priority for some funders giventheir mission constraints.

Participants did stress, however, the potentialusefulness of some efforts:

• To identify and create a comprehensivecompendium of existing resource materials.

• To consider a mechanism or centralizedsystem where interested parties couldaccess the existing information more easilythan at present.

• To try to overcome some of the problemsencountered in clinical trials, particularlydissatisfaction with outcomes on the part ofdeveloping country researchers, bypreparing a general document on ‘goodpractices’ for collaboration in clinical trialsin developing countries. This documentshould highlight certain issues that, ifproperly addressed, could maximizepositive outcomes while avoiding negativeones. Such good practices included:building in input from localcommunity/investigators into study designand results analysis; local capacity buildingthrough opportunities for training; andexplicit discussion of introducing productslocally if they proved effective in the trials.Several participants stressed the usefulnessof such a document, but it was left to theIPPPH Secretariat to consider how to setin motion a process for developingconsensus.

2.7 Closure of meeting

Dr Roy Widdus expressed sincere thanks to DrWenceslas Kilama, who chaired the meeting; theco-chairs, Dr Uford Inyang and Dr GeraldKeusch; and the working group chairs andrapporteurs for their contributions. He alsothanked all participants for their input to what hefelt had been a wide-ranging and frank exchangeon how to better work together to build strongerclinical trials capacity in LMICs, particularly inAfrica.


Friday, 15 November 2002 (Day One)

Plenary session I Chair: Dr Wenceslas Kilama ▲ Co-chair: Dr Roy Widdus

2.30 p.m. – 2.45 p.m. • Welcome and introductions• Aims of the meeting

2.45 p.m. – 3.00 p.m. • Overview: Existing assessments of current resources and future demands for clinical trials in low- and middle-income countries (LMICs) – What do we know?

• Dr Ebi Kimanani, Consultant, Rockefeller Foundation

3.00 p.m. – 3.30 p.m. • Discussion: How can we better assess current resources and future demands?

3.30 p.m. – 3.45 p.m. Break

Plenary session II Chair: Dr Wenceslas Kilama ▲ Co-chair: Dr Roy Widdus

3.45 p.m. – 5.30 p.m. • Key lessons from existing experience• Discussion, based upon synthesis of summaries of experience submitted

by LMIC participants and selected reviews

5.30 p.m. – 6.00 p.m. • Initial summary of key lessons

End of day one

Annex 1: Agenda

Chair

Dr Wenceslas Kilama, African Malaria Network Trust (AMANET), Tanzania

Co-chairs

Dr Uford Inyang, National Institute for Pharmaceutical Research and Development, NigeriaDr Gerald Keusch, National Institute of Health, United States of AmericaDr Roy Widdus, Initiative on Public-Private Partnerships for Health, Switzerland


Saturday, 16 November 2002 (Day two)

Working group sessions

8.30 a.m. – 10.30 a.m. • Discussion (in working groups): Priority needs for clinical trials capacity strengthening within and among cross-cutting areas:a) Overall managementb) Good clinical practice and quality controlc) Community relations and engagement

• Where, within and among these areas are more financial or human resources or more coordination most needed?

10.30 a.m. – 10.45 a.m. Break

Plenary session III Chair: Dr Wenceslas Kilama ▲ Co-chair: Dr Uford Inyang

10.45 a.m. – 12.00 noon • Sustaining capacity:a) The roles of institutional and government policiesb) Can pharmaco-vigilance/Phase IV studies play a role in sustaining capacity?

• Discussion

12.00 noon – 1.30 p.m. Lunch

Plenary session IV Chair: Dr Wenceslas Kilama ▲ Co-chair: Dr Gerald Keusch

1.30 p.m. – 2.00 p.m. • Conclusions of working groups(10 minutes each to report back; comments can be submitted in writing to the meeting rapporteur)

Plenary session V Chair: Dr Wenceslas Kilama ▲ Co-chair: Dr Gerald Keusch

2.00 p.m. – 3.30 p.m. • Perspectives on coordinating support to strengthening clinical trials capacity:(a) Selected funders, including industry and EDCTP(b) LMIC institutions(c) Product development partnerships

3.30 p.m. – 3.45 p.m. Break

Plenary session VI Chair: Dr Wenceslas Kilama ▲ Co-chair: Dr Roy Widdus

3.45 p.m. – 5.30 p.m. • Discussion: Next steps?(a) Beyond a meeting report,what is desirable and who should do it?

End of meeting


Dr Salim Abdulla, Ifakara Health Research andDevelopment Centre, Dar es Salaam Office –National Institute for Medical ResearchCompound, Sokoine/Luthuli Road, P.O. Box78373, Dar es Salaam, Tanzania.Tel.: 255 22 2132704; Fax: 255 22 2136687; E-mail: [email protected]

Ms Phumla Adesanya, International AIDSVaccine Initiative (IAVI), 110 William Street,New York, N.Y. 10038, USA.Tel.: 1 212 847 1076; Fax: 1 212 847 1112; E-mail: [email protected]

Prof. Bartholomew D. Akanmori, NoguchiMemorial Institute for Medical Research,University of Ghana, P.O. Box LG5681,Legon, Accra, Ghana.Tel.: 233 21 501178; Fax: 233 21 502182; E-mail: [email protected]

Dr Hannah Akuffo, SIDA/SAREC, SwedishInternational Cooperation Agency, 105 25Stockholm, Sweden.Tel.: 46 8 698 5263; Fax: 46 8 698 5656; E-mail: [email protected]

Dr Alwyn T. Andrew-Mziray, Huron ConsultingGroup – Healthcare, 550 W. Van Buren, 9th

Floor, Chicago, Il 60607, USA.Tel.: 1 312 880 3158; Fax: 1 312 583 8701; E-mail: [email protected]

Dr Danstan Bagenda, University ofWashington/Statistical Center for HIV/AIDSResearch and Prevention(SCHARP)/Makerere University-JohnsHopkins University Research Collaboration,6423 NE Radford Dr. No. 311, Seattle, WA98115, USA. Tel.: 1 206 229 9741; Fax: 1 206 667 4812/543 3286; E-mail: [email protected] –[email protected]

Ms Olamide Bandele, Nigeria Chapter, AfricanCouncil for Sustainable Health Development(ACOSHED), 20 Aare Avenue, New BodijaEstate, P.O. Box 21633, Ibadan, Oyo State,Nigeria.Tel.: 234 2 810 2401; Fax: 234 2 810 2405; E-mail: [email protected]

Dr Banson Barugahare, Joint Clinical ResearchCentre, Kampala, Plot 893 Ring RoadButikiro House – Mengo, P. O. Box 10005,Kampala, Uganda.Tel.: 256 41 270 622/256 77 430 206; Fax: 256 41 342 632; E-mail: [email protected] –[email protected]

Ms Sandra Botta, Initiative on Public-PrivatePartnerships for Health, Global Forum forHealth Research, ICC Building, 20 Route dePré-Bois, P.O. Box 1826, 1215 Geneva 15,Switzerland.Tel.: 41 22 799 4082; Fax: 41 22 41 22 4089; E-mail: [email protected]

Dr Sheick Oumar Coulibaly, LaboratoireNational de Santé Publique, Medical BiologyDepartment, 09 B.P. 24, Ouagadougou 09,Burkina Faso.Tel.: 226 37 31 31/37 32 32; Fax: 226 37 24 30; E-mail: [email protected]

Dr J. Carl Craft, Medicines for Malaria Venture(MMV), ICC Building, Block G, Third Floor,20 Route de Pre-Bois, P.O. Box 1826, 1215Geneva 15, Switzerland.Tel.: 41 22 799 4067; Fax: 41 22 799 4061; E-mail: [email protected]

Dr Rodolfo Dennis, INCLEN, Inc., PontificiaUniversidad Javeriana, Hospital San Ingnacio,Carrera 7a No 40-62 piso 2, Bogota, D.C.,Colombia.Tel.: 57 1 340 0486; Fax: 57 1 185 6981; E-mail: [email protected]

Annex 2: List of participants


Dr Jean-Pascal Ducret, Sanofi-Synthelabo/Impact Malaria, 82 AvenueRaspail, 94255 Gentilly, France.Tel.: 33 1 41 24 65 11; Fax: 33 1 41 24 61 24; E-mail: [email protected]

Dr Jose Esparza, WHO-UNAIDS HIV VaccineInitiative, World Health Organization, 20Avenue Appia, 1211 Geneva 27, Switzerland.Tel.: 41 22 791 4392; Fax: 41 22 791 4865; E-mail: [email protected]

Dr Ruth Frischer, Bureau for Global Health,USAID, 1300 Pennsylvania Avenue, N.W.,Ronald Reagan Building, Room 3.07-070,Third Floor, Washington, D.C. 20523, USA.Tel.: 1 202 712 0771; Fax: 1 202 216 3702; E-mail: [email protected]

Dr Janet Ann Frohlich, Southern Africa FogartyAIDS Training Programme, Nelson RMandela School of Medicine, University ofNatal, Private Bag 7, Congella 4013, SouthAfricaTel.: 27 31 2604277; Fax: 27 31 2604307; E-mail: [email protected]

Prof. Oumar Gaye, Faculty of Medicine,Université Cheik Anta DIOP de Dakar(UCAD), Dakar, Senegal.Tel.: 221 825 1998/637 5055; Fax: 221 825 36 68; E-mail: [email protected]

Dr Lawrence J. Geiter, Aeras Global TuberculosisVaccine Foundation, 9610 Medical CenterDrive, Suite 220, Rockville, MD 20850, USA.Tel.: 1 301 762 3100; Fax: 1 301 762 2122; E-mail: [email protected]

Dr Sam Gobin, Aids Fonds, Keizersgracht 390,1016 GH Amsterdam, The Netherlands.Tel.: 31 20 6262669; Fax: 31 20 6275221; E-mail: [email protected]

Dr Marian Griffiths, Medical, Safety andTherapeutics, Covance Inc., ClinicalDevelopment Services, 210 Carnegie Center,Princeton, NJ 08540-6233, USA.Tel.: 1 609 452 4706; Fax: 609 734 9208; E-mail: [email protected]

Dr Tony Hawkridge, Sequella/UCT BCG Trial,Child Health Unit, Department of Paediatricsand Child Health, University of Cape Town,46 Sawkins Road, Rondebosch 7700, CapeTown, South Africa.Tel.: 27 21 685 4103; Fax: 27 21 689 5403; E-mail: [email protected]

Ms Christina Heiler, INCLEN, Inc., 1420Walnut Street, Suite 411, Philadelphia, PA19102-4003, USA.Tel.: 1 215 222 7700; Fax: 1 215 222 7741; E-mail: [email protected]

Dr Carole A. Heilman, National Institutes forHealth, NIAID/DMID, 6700B RockledgeDrive, Room 3142, MSC 7630, Bethesda,MD 20892-7630, USA.Tel.: 1 301 496 1884; Fax: 1 301 480 4528; E-mail: [email protected]

Dr Rodney Hoff, National Institute of Allergyand Infectious Disease, National Institute forHealth, Bethesda, MD 20892-7628, USATel.: 1 301 496 6179; Fax: 1 301 402 3684; E-mail: [email protected]

Prof. Michael Hollingdale, London School ofHygiene and Tropical Medicine, Gates MalariaProgram, 50 Bedford Square, London WC1B3DP, United Kingdom.Tel.: 44 207 299 4714; Fax: 44 207 2994720; E-mail: [email protected]

Dr Andreas Holtel, European Commission,Office SDNE 7/36, Rue de la Loi 200, 1049Brussels, Belgium.Tel.: 32 2 295 3716; Fax: 32 2 295 5365; E-mail: [email protected]

Dr Joachim Hombach, Government Affairs,GlaxoSmithKline Biologicals, 89 Rue del’Institut, 1330 Rixensart, Belgium.Tel.: 32 2 656 70 80; Fax: 32 2 656 81 45; E-mail: [email protected]

Dr Akira Homma, Bio-Manguinhos, FundacaoOswaldo Cruz, Av. Brasil 4365, Manguinhos21045-900, Rio de Janeiro, RJ, Brazil.Tel.: 55 21 3882 9305; Fax: 55 21 22604727; E-mail: [email protected]


Dr Uford Inyang, National Institute forPharmaceutical Research and Development(NIPRD), Idu Industrial Area, P.M.B. 21,Garki, Abuja, Nigeria.Tel.: 234 9 5239089/234 9 6700834; Fax:234 9 5231043/0804 418 0278; E-mail: [email protected]

Dr Rajiv Kumar Jain, Infectious DiseasesChapter, Indian Academy of Pediatrics, 480Sector 37, Faridabad–121003, Haryana, India.Tel.: 91 11 3002256; Fax: 91 11 3387556; E-mail: [email protected]

Dr Soren Jepsen, European Malaria VaccineInitiative (EMVI), c/o Statens Serum Institut,5 Artillerivg, 2300 S Copenhagen, Denmark.Tel.: 45 3268 3188; Fax: 45 3268 3228; E-mail: [email protected]

Dr Amina Jindani, International Union AgainstTuberculosis and Lung Disease, 68 BoulevardSaint-Michel, 75006 Paris, France.Tel.: 33 1 44 32 03 66; Fax: 33 1 43 29 90 87; E-mail: [email protected]

Dr Luis Jodar, International Vaccine Institute,Shillim-dong, San 56-1, Kawnak-ku, SeoulNational University Campus, Seoul, Republicof Korea.Tel.: 82 2 872 2801; Fax: 82 2 872 2803; E-mail: [email protected]

Dr Saidi H. Kapiga, Harvard School of PublicHealth, 665 Huntington Avenue, Bldg 1Room 1105, Boston, MA 02115, USA.Tel.: 1 617 432 1237; Fax: 1 617 566 0365; E-mail: [email protected]

Mr Andrew Kennedy, Department of ResearchPolicy and Cooperation, World HealthOrganization, 20 Avenue Appia, 1211 Geneva27, Switzerland.E-mail: [email protected]

Dr Nzeera Ketter, International AIDS VaccineInitiative (IAVI), 110 William Street, NewYork, N.Y. 10038, USA.Tel.: 1 650 854 9806; Fax: 1 650 854 1076; E-mail: [email protected]

Dr Gerald Keusch, Fogarty International Center,National Institutes of Health, 31 CenterDrive, Bethesda, MD 20892-2220, USA.Tel.: 1 301 496 1415; Fax: 1 301 402 2056; E-mail: [email protected]

Dr Marie-Paule Kieny, Initiative for VaccineResearch, Vaccines and Biologicals, HealthTechnology and Pharmaceuticals, WorldHealth Organization, 20 Avenue Appia, 1211Geneva 27, Switzerland.Tel.: 41 22 791 3591; Fax: 41 22 791 4860; E-mail: [email protected]

Dr Wenceslas L. Kilama, African MalariaNetwork Trust (AMANET), C26/27Tanzania Commission for Science andTechnology Building, P. O. Box 33207, Dar esSalaam, Tanzania.Tel.: 255 22 270 0018; Fax: 255 22 2700380; E-mail: [email protected] (Chair)

Dr Ebi Kimanani, Ebitendo Statistics Inc.,Beaconsfield, QC H9W 5B6, Canada.Tel.: 1 514 697 5902; Fax: 1 514 697 6597; E-mail: [email protected]

Dr Ivana Knezevic, Quality Assurance and SafetyBiologicals, Vaccines and BiologicalsDepartment, World Health Organization, 20Avenue Appia, 1211 Geneva 27, Switzerland.Tel.: 41 22 791 31 36; Fax: 41 22 791 49 71; E-mail: [email protected]

Mr Gunnar Kvale, Centre for InternationalHealth, Armauer Hansen Building, Universityof Bergen, 5021 Bergen, Norway.E-mail: [email protected]

Dr Richard Lane, The Wellcome Trust, 183Euston Road, London NW1 2BE, UnitedKingdom.Tel.: 44 207 611 7230; Fax: 44 207 6110681; E-mail: [email protected]

Dr Valerie Lameyre, Sanofi-Synthelabo/ImpactMalaria, 82 Avenue Raspail, 94255 Gentilly,France.Tel.: 33 1 41 24 63 64; Fax: 33 1 41 24 61 24; E-mail: valé[email protected]

Dr Juntra Laothavorn, Product Research andDevelopment, Special Programme forResearch and Training in Tropical Diseases,World Health Organization, 20 Avenue Appia,1211 Geneva 27, Switzerland.Tel.: 41 22 791 3867; Fax: 41 22 791 4854; E-mail: [email protected]


Dr Janis K. Lazdins-Helds, Product Researchand Development, Special Programme forResearch and Training in Tropical Diseases,World Health Organization, 20 Avenue Appia,1211 Geneva 27, Switzerland.Tel.: 41 22 791 3818/3817; E-mail: [email protected]

Prof. Rose Leke, Faculty of Medicine andBiomedical Sciences, University of Yaounde 1,Yaounde, Cameroon.Tel.: 237 223 7429/237 222 5955; Fax: 237223 7429; E-mail: [email protected] –[email protected]

Dr William Macharia, INCLEN, Inc.,University of Nairobi, Clinical Epidemiology,P.O. Box 19676, Nairobi, Kenya.Tel.: 254 2 713 462; Fax: 254 2 710 164; E-mail: [email protected]

Dr Isaac Malonza, Department of ReproductiveHealth and Research, World HealthOrganization, 20 Avenue Appia, 1211 Geneva27, Switzerland.Tel.: 41 22 791 3641; Fax: 41 22 791 4171; E-mail: [email protected]

Prof. Keith P.W.J. McAdam, Medical ResearchCouncil Laboratories, P. O. Box 273, Banjul,Gambia.Tel.: 220 496 715; Fax: 220 496 513; E-mail: [email protected]

Dr Martin Meremikwu, Department ofPaediatrics, University of Calabar, G.P.O. Box1211, Calabar, Nigeria.Tel.: 234 8777 6512; Fax: 234 8721 0403; E-mail: [email protected] –[email protected] –[email protected]

Dr Mark Miller, Division of InternationalEpidemiology & Population Studies, NationalInstitutes of Health, Fogarty InternationalCenter, 16 Center Drive MSC 6705,Bethesda, MD 20892-6705, USA.Tel.: 301 496 0815; Fax: 301 496 8496, E-mail: [email protected]

Ms Jessica B. Milman, Malaria Vaccine Initiative,PATH, 6290 Montrose Road, Suite 1000,Rockville, MD 20852, USA.Tel.: 301 770 5377; Fax: 301 770 5322; E-mail: [email protected]

Dr Declan Mulkeen, Medical Research Council,20 Park Crescent, London W1B 1AL, UnitedKingdom.Tel.: 44 207 636 5422; Fax: 44 207 74365229; E-mail:[email protected]

Dr Mary Newton, Medical PharmaceuticalDivision, Roche Products (Pty) Ltd., P.O. Box129 Isando 1600, 4 Brewery Street, Isando,South Africa.Tel.: 27 11 928 8870; Fax: 27 11 392 4144; E-mail: [email protected]

Dr Andrew Nunn, Clinical Trials Unit, MedicalResearch Council, 222 Euston Road, LondonNW1 2DA, United Kingdom.Tel.: 44 207 670 4703; Fax: 44 207 6704815; E-mail: [email protected]

Dr Opokua Ofori-Anyinam, GlaxoSmithKlineBiologicals, Rue de l’Institut 89, 1330Rixensart, Belgium.Tel.: 32 2 656 9863; Fax: 32 2 656 6160; E-mail: [email protected]

Dr Sonia R. Pagliusi, Vaccines and Biologicials,Health Technology and Pharmaceuticals,World Health Organization, 20 Avenue Appia,1211 Geneva 27, Switzerland.Tel.: 41 22 791 4265; Fax: 41 22 791 4860; E-mail: [email protected]

Prof. K. J. Pallangyo, Faculty of Medicine,Muhimbili University College of HealthSciences, P.O. Box 65001, Dar es Salaam,Tanzania.Tel.: 255 22 2151680; E-mail:[email protected]

Dr Bernard Pecoul, Médecins sans FrontièresCampaign for Access to Essential Medicines,12 Rue du Lac, 1207 Geneva, SwitzerlandTel.: 41 22 849 8405; Fax: 41 22 849 8404; E-mail: [email protected] –[email protected]

Ms Beth Peterman, Bill and Melinda GatesFoundation, P.O. Box 23350, Seattle, WA98102, USA.Tel.: 1 206 709 3293; Fax: 1 206 709 3170; E-mail: [email protected] –[email protected]


Dr Regina Rabinovich, Malaria VaccineInitiative, PATH, 6290 Montrose Road, Suite1000, Rockville, MD 20852, USA.Tel.: 1 301 770 5377; Fax: 1 301 770 5322; E-mail: [email protected]

Dr Rolf Reed, University of Bergen, HaraldHarfagresgate 1, 5009 Bergen, Norway.Tel.: 47 5558 6389; Fax: 47 5558 6230; E-mail: [email protected]

Dr Rob Ridley, Product Research andDevelopment, Special Programme forResearch and Training in Tropical Diseases,World Health Organization, 20 Avenue Appia,1211 Geneva 27, Switzerland.Tel.: 41 22 791 3767; E-mail: [email protected]

Dr Lise Riopel, Medicines for Malaria Venture(MMV), ICC Building, Block G, Third Floor,20 Route de Pre-Bois, P.O. Box 1826, 1215Geneva 15, Switzerland.Tel.: 41 22 799 4070; Fax: 41 22 799 4061; E-mail: [email protected]

Dr Anita Rønn, Department of InternationalHealth/University of Copenhagen,Blegdamsvej 3B, The Panum Institute, 2200-Copenhagen N, Denmark.Tel.: 45 35 32 78 35; Fax: 45 35 32 78 35; E-mail: [email protected]

Dr Giorgio Roscigno, Strategic Development,The Global Alliance for TB DrugDevelopment, 27 Boulevard Bischoffsheim,1000 Brussels, Belgium.Tel.: 32 2 210 0220; Fax: 32 2 223 6928; E-mail: [email protected]

Dr Jacobo Sabbaj, Merck & Company, Inc., 126East Lincoln Avenue, Maildrop: RY 34-A100,Rahway, NJ 07065, USA.Tel.: 1 732 594 5520; 1 732 594 6580; E-mail: [email protected]

Dr Osman A. Sankoh, Indepth Network, 9Adenkum Loop, P.O. Box KD 213, Kanda,Accra, Ghana.Tel.: 233 21 254752; Fax: 233 21 254752; E-mail: [email protected]

Dr Abha Saxena, Department of Research Policyand Cooperation, World Health Organization,20 Avenue Appia, 1211 Geneva 27, Switzerland.Tel.: 41 22 791 2406; Fax: 41 22 791 4169; E-mail: [email protected]

Dr Sally Stansfield, Bill and Melinda GatesFoundation, P.O. Box 23350, Seattle, WA98102, USA.Tel.: 1 206 709 3293; 1 206 709 3170; E-mail: [email protected] –[email protected]

Dr Coumba Toure Kane, Laboratoire deBacteriologie-Virologie, CHU Aristide LeDantec, B.P. 7325, Dakar, Senegal.Tel.: 221 8216420/8225919/6372266; Fax: 221 8216442; E-mail: [email protected]

Prof. Thorkild Tylleskar, Centre for InternationalHealth, Armauer Hansen Building, Universityof Bergen, 5021 Bergen, Norway.Tel.: 47 55 97 49 75; Fax: 47 55 97 49 79; E-mail: [email protected]

Dr Henrietta Ukwu, Merck ResearchLaboratories, P.O. Box 4, BLB-22, WestPoint, PA, USA.Tel.: 1 484 344 7176; Fax: 1 484 344 3602; E-mail: [email protected]

Dr Lut Van Damme, Contraceptive Research andDevelopment Program (CONRAD), 1611North Kent Street, Suite 806, Arlington, VA22209, USA.Tel.: 1 703 276 4020; Fax: 1 703 524 4770; E-mail: [email protected]

Dr Remko Van Leeuwen, Business Development,International Antiviral Therapy EvaluationCentre (IATEC), University of Amsterdam,Academic Medical Centre, P.O. Box 22700,1100 DE Amsterdam, The Netherlands.Tel.: 31 20 566 7158; Fax: 1 240 757 7091; E-mail: [email protected]

Dr Roy Widdus, Initiative on Public-PrivatePartnerships for Health, Global Forum forHealth Research, ICC Building, 20 Route dePré-Bois, P.O. Box 1826, 1215 Geneva 15,Switzerland.Tel.: 41 22 799 4088/4086; Fax: 41 22 41 22 4089; E-mail: [email protected]


Summary

Assessment of clinical trials capacities in

Africa

Amajor hindrance to clinical trials in Africa is ageneral lack of knowledge of its scope and

potential including the existence of trainedinvestigators and the level of governmentregulations in the continent. This issue was thepurpose of a baseline survey conducted in EastAfrica by Ebitendo Statistics and funded by theRockefeller Foundation in 2001 to map thecurrent status of clinical research with specialemphasis on clinical trials in the region.

The survey’s results were (or will be) published in:• Kimanani, E. (2002) “Current status of

clinical trials in Kenya”, Drug InformationJournal, 36.1: 1–39 (http://www.dia.org).

• Kimanani, E. (2001) “Good ClinicalPractice: A call for regional harmonizationof the GCP guideline”, East AfricanMedical Journal, Nov.

• Kimanani, E. “A database of investigatorsand clinical trials in East Africa”, DrugInformation Journal (under preparation).

They are also presented in the form of a databaseof investigators and investigative sites, available onthe Internet (http:www.ebitendo.com/members)for easy access by potential sponsors. The databaseis only a first component to a site managementorganization that is being built by EbitendoStatistics.

Based on this survey, the following observations,results and recommendations are made:

• The potential for clinical trials exists.This is evidenced by a critical mass ofindividuals with solid academic training inthe clinical sciences. A framework forperforming academic types of research alsoexists. However, there is still muchregulatory work to do to build a framework

for clinical trials that meets globalstandards. At present, much of the conductof clinical trials is sporadic and left to thediscretion of the principal investigatorand/or the sponsor.

• Political will towards clinical trials existsbut is distracted. Governments in theregion have shown some initiative inpromoting clinical research by setting upresearch institutions with the generalmandate to carry out medical research forinnovation and especially to influencepublic policy. Examples of these institutionsare the National Institute for MedicalResearch (NIMR), in Tanzania, the JointClinical Research Center (JCRC) inUganda, the Kenya Medical ResearchInstitute (KEMRI) in Kenya, and theNational Institute for PharmaceuticalResearch (NIPRD) in Nigeria. Theseinstitutions have been responsible forraising the general public’s awareness of theadvantages of clinical research, providingvenues for local scientists to pursue clinicalresearch investigations and, to some extent,influencing public policy.

• Medical practitioners in remote areaswho have the potential to be clinicalinvestigators feel isolated from the coreof clinical research, facilities, fundingand decision-making. According to thesepeople, almost all clinical studies in theircountries take place in one or twoinstitutions usually located close to thecapital city. This is unfortunate given thatremote areas tend to have patientpopulations with little or no access to careand attention. In addition, the patientswould be suitable for clinical studiesbecause they are drug-free. In some sitesjust 30 km from the cities, the survey wasthe first time that anyone had shown aninterest in them.

Annex 3: Building a platform for clinical trials

in Africa


• Facilities for handling and managingclinical trial data are minimal at best,especially compared to global standards.Subject-screening tools and facilities andbiological sample-handling laboratories arelimited to the research institutions (~1 percountry), medical training institutionshospitals (~1–3 per country) and nationalhospitals (~1 per country). Data processingand reporting are largely left to individuals.

• Logistics involved in conducting clinicaltrials in several sites in the region arechallenging but can be overcome.Transportation and communication issuesremain challenging in this region as in mostdeveloping areas. Air travel between themajor cities generally exists, although airlinks within each country is not assured.Most of the remote areas can be reached byroad with a reliable vehicle.Communication in most areas is possibleby cell phones.

• Cultural factors are significant issues tobe taken into consideration whenplanning and conducting clinical trialsin this region and in Africa in general.As long as a study is seen to be from the‘outside’, acceptance and cooperation maynot be as forthcoming as they may seem.

• Current methods of sponsoring studiesdo not deliberately foster self-sufficiencyand capacity building. The reasons aremulti-factorial but may be largely due tothe lack of indigenous drug development,lack of financial resources, insufficientpolitical support and questionable motivesof the sponsors.


Dr Lise Riopel, Medicines for Malaria Venture (MMV), Geneva, Switzerland

A survey questionnaire on lessons from prior experiences of conducting clinical trials in LMICs was sentto invitees who had either worked in or were from these countries.

Reponses were received from the following:

Name Affiliation

Dr Osman Sankoh INDEPTH Network, GhanaProf. Dicky Akanmori Noguchi Memorial Institute for Medical Research, GhanaProf. Oumar Gaye Faculty of Medicine, Université Cheik Anta DIOP de Dakar

(UCAD), SenegalDr Coumba Toure Kane Laboratoire de Bactériologie-Virologie, Dakar, SenegalDr Roberto Badaro Federal University of Bahia, BrazilDr Harriet Mayanja-Kizza Department of Medicine, Makerere University Medical School,

UgandaDr Danstan Bagenda (Uganda) University of Washington/Statistical Center for HIV/AIDS

Research and Prevention (SCHARP)/Makerere University-JohnsHopkins University Research Collaboration

Dr Demissie Habte Former Director, International Centre for Diarrhoeal DiseaseResearch (ICDDR), Bangladesh

Dr Tony Hawkridge Child Health Unit, University of Cape Town, South AfricaDr Wenceslas L. Kilama Managing Trustee, African Malaria Network Trust (AMANET)Dr John Clemens International Vaccine Institute, Seoul, Republic of KoreaProf. Keith McAdam Director, Medical Research Council Laboratories, GambiaMs Christina Heiler INCLEN, Inc., Philadelphia, USA

The issues most often raised in responses to the survey included:• The need for more training in GCP and study management, including the possible addition of

clinical research to academic curricula.

• The role of the trial sponsor in GCP training.

• The need for experienced study coordinators, how to increase their availability and ensure thesustainability of this resource.

• Ethical review: the need for further definition; at present, understanding of procedures andprocesses often takes too long.

• Communication difficulties, particularly in rural settings.

Annex 4: Summary of survey of lessons learned


1. Overall 2. Good clinical 3. Community

management practice (GCP) and relations and

quality control engagement

Dr Mary Newton Dr Danstan Bagenda Prof. Keith McAdamMr Andrew Kennedy Dr Isaac Malonza Dr Coumba Touré-KaneDr Andreas Holtel Dr Andrew Nunn Prof. Rose LekeDr Nzeera Ketter Dr Martin Meremikwu Dr Amina JindaniDr Alwyn Andrew-Mziray Dr Joachim Hombach Dr Richard LaneDr Ruth Frischer Ms Phumla Adesanya Dr José EsparzaMs Christina Heiler Dr Tony Hawkridge Dr Janet FrohlichDr Salim Abdulla Dr Rob Ridley Dr Gerard KeuschDr Regina Rabinovich Dr Ivana Knezevic Dr Rod HoffDr Carole Heilman Dr Hannah Akuffo Dr Ebi KimananiDr Luis Jordar Dr Marian Griffiths Ms Olamide BandeleDr Uford Inyang Dr Henrietta Ukwu Dr Osman SankohDr Remko Van Leeuwen Dr Banson Barugahare Ms Sandra BottaDr Sam Gobin Dr Giorgio RoscignoProf. Bartholomew Akanmori Dr Rodolfo DennisDr Lise Riopel Prof. Michael HollingdaleDr Rajiv Kumar Jain Dr Lut Van DammeMs Jessica Milman Dr Anita RønnDr Opokua Ofori-Anyinam Prof. Oumar GayeDr Jacobo Sabbaj Dr Larry Geiter

Annex 5: List of participants in working groups


1. Overall 2. Good Clinical 3. Communitymanagement Practice (GCP) and relations and

quality control engagement

• Site characterization • Ethical review • Ethical reviewand baseline studies • Training • Social and behavioural

• Projects start-up/operations • Project start-up/operation aspects of clinical • Financial management • GCP adherence research/clinical trial• Management community • Regulatory requirements • Size characterization

relations • Data records management • Informed consent• Data records management • Statistical and data analysis • Unexpected problems• Coordination with partners • Unexpected problems• Training• Staffing• Communication• Ethical review committee

management• Unexpected problems

Co-chairs: Co-chair: Co-chairs:Prof. Bartholomew Akanmori Prof. Oumar Gaye Dr José EsparzaDr Lise Riopel Dr Osman Sankoh

Rapporteur: Rapporteur: Rapporteur:Dr. Gina Rabinovich Dr Lawrence Geiter Dr Janet Frohlich

Annex 6: Topics assigned to working groups


Major issues identified

Trial-specific issues

• Characterization: certain corecharacteristics need to be identified, such aspolitical will; in addition, a baselinesurveillance system that will definedemographics and baseline incidence ofdisease is needed. How are patient orvolunteer populations identified? –— Disease-specific issues: it could be

important to involve groups that accessprogrammes for retroviral care.

• It is useful to do observational studies thatenable a new site to develop training andcapacities.

• Good laboratory practice (GLP) andtraining for staff: these usually come afterepidemiology and surveillance asinvestigators know less about what therequirements are. This is balanced by theincreased need for central laboratories. –— Everything needs to be done – but it is

important to prioritize. WHO’s TDRtalks about ‘GCP laboratory’. GLP isvery expensive and is something thatlaboratories should aspire to.

• The standard of medical care in thepopulation needs to be raised.

• A long timescale: it takes years to set theinfrastructure up and then prepare for thestudies.

Cross-disease, cross-site management

issues

• Management of expectations as to when asite is ready (and for what?).

• There should be a body/organizationcharged with continuous education onaspects of GLP and GCP.

• What is a site? It can vary enormously: is itan institution that has already started work?

Hospitals? Given existing infrastructure,what needs to be added to make a site?What is the relationship between a ‘site’and an institution? –— The European Union’s EDCTP can be

useful in classifying sites. But it shouldnot be forgotten that in order toenhance capacity, it first needs to beassessed.

• Accreditation for laboratories is required.But should accreditation be under theauspices of the government or the privatesector? In most African countries, thereference laboratory system is part ofgovernment. Should this be independent toavoid potential corruption?

• Key management issues include the factthat, in a few sites, multiple sponsors arefunding the trial and each has their ownstandard for financial reporting. There is aneed for adequate control measures andtransparency. It would be useful to have aset of broad principles for use in differentsites. How to charge some costs acrossdifferent trials? Procedures should beacceptable both in a given country and todonors, and should be audited. Corruptioncan be organized , widespread and ‘subtle’.A clear understanding of what is culturallyexpected and acceptable to funders istherefore necessary.

• Data management: –— Issues of varying standards also affect

different standards to which datamanagement needs to be held – is it fora pivotal trial for granting a license? Towhose regulatory standard?

–— South Africa has developed datamanagement capacity, which is locallydriven when it is a local priority.

• It is important to establish trials thatundertake several types of studies, i.e.,

Annex 7a: Report of the working group on overall

management


vaccines and microbicides. However, themanagement of multi-site and multi-diseasesites needs to be discussed further.

• Sustainability of clinical trial sites: historicalexperience already exists and gives an ideaof what may happen after a key trial hasended. What would increase the likelihoodof extension and growth of sites? How toprevent languishing of sites that havealready been established?

• Communication between funders and sites:it is important to designate leaders/leadorganization, not just with donor(s), butalso with the community. Coordinationrequires not only access to e-mail or fax,but an awareness that everyone can bringup issues. –— A study coordinator and study monitor

are needed. Face-to-facecommunication is best for many issues,but there needs to be a commmitmentfrom all players to make this happen.

• Ethical review management: Many donors,etc., are coming into countries and tryingto help with workshops, etc. How to getthe various groups together? Whilestandards are the same, SOPs in manycountries may vary. There is little thoughtof age and gender balance in manycountries. The International ClinicalEpidemiology Network (INCLEN) inIndia has set up its own review board.

In general, the group suggested that manyproblems arose from what it terms a ‘hit-and-run’historical approach to trials in Africa.



Ethical review

• Institutional Review Boards (IRBs) doexist. They approve or disapprove newtrials.

• IRB review of ongoing trials is, however,weak.

• Data and safety monitoring committees:–— Their capacity is weak to non-existent. –— Their roles are poorly understood.–— Independent experts are lacking.

Ethical review/Regulatory authority

• Very weak and underfunded.

• Some countries have national GCPguidelines.

• “The FDA [Food and DrugAdministration] is your friend.” Consultearly and often to avoid problems

General training

• Start early, in academic and pre-trialprogrammes.

• Create a baseline understanding andculture of clinical research, e.g., P>.05 is afailed/negative trial.

Training

• “Knowledge is power”.

• Trial-specific training starts with protocoldevelopment.

• Early training at all levels is important.

• Training should be continuous, and flowsfrom monitoring.

• Multiple courses already exist.

• Regional networks could catalogue andidentify gaps.

• Some trainees should fail.

• Certification/compensation/profession.

Trials and monitoring

• Strict adherence needed for registration.

• Could it be relaxed for Phase IV trials?

• Early involvement of local investigatorshelps avoid problems (e.g., lab results in 24hours).

• Protocol and SOP are the basis for audits.

• Monitor early and often, and train on thebasis of audit results.

Guidelines of best practices of clinical trial

sponsorship

• Industry.

• Governmental and internationalorganizations.

• Alliances, forums, foundations.

Annex 7b: Report of the working group on Good

Clinical Practice (GCP) and quality control



Emerging issues

• Community participation and preparation.

• Establish social contract with community.

• Ethics at a community level.

• Social and behavioural aspects of clinicalresearch.

• ‘Informed consent’.

Overriding principles

• Community preparation and participationbenefit both community and science, anddefine the outcome of the research.

• Ethics and community preparation areintegral to scientifically sound research.

Community participation and preparation

• Define ‘community’:–— Two levels:

◆ Higher/macro◆ Community/micro

–— Pool of people from which the studypopulation is drawn.

–— Popular-opinion leaders and decision-makers including health serviceproviders.

• Define community in context of research:–— Phase I and II trials versus Phase III and

IV trials.–— Type of research impacts of stigma and

discrimination at both individual andcommunity level.

• Mechanisms to engage community:–— Need for a clear strategy:

◆ Integral part of R&D process.◆ Investment begins prior to trial.◆ Not a process for damage control.

–— First need national-level support forresearch agenda.

–— Parallel process of negotiation andconsultation at levels of:◆ Authority and government.◆ Civil society/local

government/nongovernmentalorganizations (NGOs).

◆ Community.

• Community concerns: –— Strengthen and build on existing

community structures anddevelopment.

–— Transparent communication, interactivedecision-making and regular informationdissemination help build trust.

–— Identify community understanding andexpectations.

–— Financial investment – who pays forcommunity preparation strategies?

Establish social contract with community

• Empowerment and enablement training;build knowledge and understanding ofresearch process.

• Research relevant to community.

• Communities face multiple choices in themerging international research agenda:mother-to-child transmission (MTCT);microbicides; vaccines, tuberculosis (TB)and antiretrovirals (ARV).

• Understanding of benefits during and aftertrials.

• Recognition of community and individualaltruistic responses. Communities desireand choose to contribute to their ownbenefit.

• Shift from conducting research on peopleto with people from research subjects toresearch participants/volunteers.

• Explore immediate benefits versus long-term benefits with community.

• Gain community support.

Annex 7c: Report of the working group on

community relations and engagement


Ethics at community level

• Issues to be addressed:

–— What does ‘equivalent protection’mean?

–— Do the available guidelines adequatelyaddress the notion of ‘communityconfidentiality’?

–— Avoid ethical imperialism: How toestablish a mechanism to hear the voiceof vulnerable populations?

• Good guidelines are available. Helpcommunities to be able to interpret theseguidelines. Need for virtual guidelines.

• Need for external advisory body to guideethical decision-making:–— Local needs to be supported through

training and resources.–— Expand existing case books to capture

local context.

• Critical issue in international research:–— Multiple trial sites need a mechanism to

establish communications between theIRBs that set up common assuranceprocesses.

• Who should provide support and buildcapacity of ethical review committees andIRBs? Should funding be a direct cost fordoing research?

Social/behavioural/ethnographic aspects of

clinical research

• Should be part of community preparationstrategy.

• Explore understanding, perceptions andexperiences of research.

• Determine decision-making mechanisms.• Understanding of autonomy.

‘Informed consent’ versus ‘informed

decision-making’ versus ‘genuine consent’

• Consent cannot be ‘informed’ asparticipants do not have access to allinformation pertaining to the study tomake a truly ‘informed choice’.

• Seek consent when assured person has beenprovided with adequate information tounderstand critical aspects of the study.

• ‘Informed decision-making’ is a processand includes involving the community,opinion leaders and individuals indevelopment of ‘genuine consent’ tool.

• Do not assume that illiterate and vulnerablepopulations cannot make a choice andprovide ‘genuine’ consent.

Where, within and among these areas, are

more financial or human resources or more

coordination most needed?

The working group emphasized the need forfinancial investment in a clearly definedcommunity education and preparatoryprogramme that addresses the five key emergingissues and that is an integral part of the scientificagenda.


Assessment tool of Covance Inc.

Provided by Dr. Marian Griffiths, Covance Inc.,Princeton, NJ, USA.

Investigator

• Therapeutic area/specialty training andexperience (with respect to both thetherapeutic area and participating in clinicaltrials).

• Appropriate medical (or dental, if relevant)qualifications, current registration topractise, specialist training if applicable, andexperience in conducting studies. A recentCV (within the past two years) is checked,and licensing is verified with the applicablelicensing board. The investigator mustshow affiliation with the investigator sitebeing considered (e.g., hospital admittingprivileges or affiliation with a clinic).

• Preference is generally given toinvestigators who have assisted withfeasibility or protocol development, or whohave worked successfully with Covance orthe sponsor in the past, or who areconsidered experts in their field.

• Restricted and/or debarred investigatorsare excluded (this is checked withapplicable regulatory authorities).

• Review of any previous regulatory auditfindings to see if any findings would lead toexclusion.

• Interest in participating in the study;competing studies (which might siphon offotherwise eligible patients).

• Appropriate and available patient populationfor the required recruitment rate.

Other staff at investigator site

• Degree of delegation to other staff andhow other staff will be supervised.

Qualifications; licensing and/or specialtytraining of staff (as applicable), includingsub-investigators.

• Experience of study coordinator(s).

• Experience and qualifications ofadministrative support staff.

• Degree of staff turnover especially forcrucial positions such as co-investigatorsand site coordinator(s).

• Flexibility of coverage (e.g., for a hospital-based emergency type indication, will staffbe available 24 hours a day?).

Source documentation practices

• Adequacy of source documentationpractices; assurance that monitors, auditorsand regulatory authorities will have directaccess to source documents.

• Suitable storage facilities which can assurelong-term storage of trial documents in asecure environment, protecting patientconfidentiality.

Laboratory and specialized diagnostic

equipment

• Availability of any required specialdiagnostic tools and/or laboratoryfacilities.

• Laboratory appropriately licensed oraccredited; lab equipment should becalibrated regularly – good laboratorypractices followed.

• Familiarity with specific questionnaires(e.g., psychometric testing) that may berequired by the protocol (this is not usuallynecessary as training on testing instrumentsis conducted prior to study start-up).

• Availability of suitable ancillary personnel(for example, independent psychometricassessor if required, etc.).

Annex 8: Criteria for assessing sites for clinical trials


The facility

• Suitable facility (exam rooms or wards,etc.).

• Suitable storage for study medication (e.g.,freezer or refrigerator if required;controlled-temperature room withthermometer and temperature log).

• Available space for storage of records,archiving records (for two to five years) –adequate space; secure; restricted access;respects patient confidentiality.

• Suitable space for monitor to review sourcedocumentation.

Ethics requirements

• IRB or IEC including list of members andtheir qualifications, the meeting scheduleand the timelines for meeting, review andresponse.

• Adequacy of Informed Consent proceduresand documentation of informed consent.The subject must be given information onall reasonably foreseeable potential risks andinconveniences and potential benefitsassociated with the study, alternate availabletreatments and the purpose(s) of the study,and must be given an adequate opportunityto ask questions. Consent must be fullyvoluntary with no coercion; the consentprocedure must be conducted in thesubject’s language; and the adequacy of theconsent procedure must be documented byan impartial witness.

• A Standard Operating Procedure shoulddocument the process of giving andreceiving informed consent.

Requirements based on GCP and/or past

experience

• Familiarity of site staff with Good ClinicalPractice (GCP), Declaration of Helsinkiand other applicable regulations.

• Familiarity with requirements andprocedures for maintaining blinding.

• Familiarity with protocol deviationprocedures (requirement fordocumentation of approval and for keepingdeviations to an absolute minimum).

• Understanding of the particular protocoland its requirements.

• Agreement to ongoing training of studypersonnel on study protocol and GCP (thiswill be provided by sponsor or contractresearch organization (CRO)).

• Agreement to provide access for periodicmonitoring and auditing of study sites toassure compliance and adequate recordkeeping.

• Familiarity with adverse event reporting,including serious adverse eventdocumentation and reporting tosponsor/CRO within 24 hours; alsofamiliarity with endpoint reporting ifapplicable.

Study drug requirements

• Reliable method of receiving and storinglab kits; reliable means of processing,labelling, storing and sending samples (e.g.,blood samples).

• Who will maintain drug? Storage andcontrol of study drug; maintenance ofrecords for administering drug; control ofdrug in secure environmentally-controlledfacility, with monitoring of temperatureand/or humidity if required; trackedmethod of controlling temperature, etc. Isthe storage capacity adequate? Is it secure(drug cannot be removed for otherpurposes)?

• Method of tracking receipt, preparation,dispensation, inventory and return of studydrug (and other supplies).

• Awareness that study drug may not be usedfor any other purposes and must berepresented as investigational only.


These materials are available on request from the Initiative on Public-Private Partnerships for HealthE-mail: [email protected]

Presentations

Clinical Trials in Low-Income Countries (Powerpoint slides)Clinical Trial Capacity in Low- and Middle-Income Countries (LMIC): Current, Potential and FutureNeeds (Word document)Dr Ebi Kimanani, Ebitendo Statistics Inc., Beaconsfield, Canada.

Good Clinical Practice (GCP): Why So Critical to Industry? (Powerpoint slides)Dr Henrietta Ukwu, Merck Research Laboratories, West Point, PA, USA.

European and Developing Countries Clinical Trials Partnership (Powerpoint slides) Professor Michael Hollingdale, London School of Hygiene and Tropical Medicine, Gates MalariaProgram, London, United Kingdom.

Major NIAID Programs in International Health (Powerpoint slides)Dr Rodney Hoff, National Institute of Allergy and Infectious Disease, National Institute for Health,Bethesda, MD, USA.

Issues Most Often Raised in The Questionnaire of Experiences and Lessons Learned (Powerpoint slides);responses available.Dr Lise Riopel, Medicines for Malaria Venture (MMV), Geneva, Switzerland.

Workshop on Clinical Trials Capacity in Low- and Middle-Income Countries: Experiences, Lessons Learnedand Priorities for Strengthening (Powerpoint slides)Dr Roy Widdus, Initiative on Public-Private Partnerships for Health, Global Forum for HealthResearch, Geneva, Switzerland.

Other documents

Clinical Research Training Project Description (Word document)Sequella Global TB Foundation Projects in the Western Cape Province of South Africa (Word document)Dr Lewellys Barker, Sequella Global Tuberculosis Foundation (now Areas Global TB VaccineFoundation), Rockville, MD, USA.

Annex 9: Presentations and other documents

The aim of the Initiative on Public-Private Partnerships for Health

is to increase the ef fec tive ness of public-pri vate col lab o ra tion,

particularly by helping those seeking to develop health products,

or to improve access to such products needed to fi ght neglected

dis eas es and other health prob lems in developing coun tries.

Created in 2000 in Geneva, Switzerland, the Initiative on Public-

Pri vate Part ner ships for Health is spon sored by the Bill and

Melinda Gates Foundation, the Rockefeller Foun da tion and the

World Bank. It operates under the aegis of the Global Forum

for Health Re search, an in de pend ent in ter na tion al foun da tion

help ing to correct the 10/90 gap in health research, from which

it also receives sup port (www.globalforumhealth.org).

Initiative on Public-Private Part ner ships for Health

International Center Cointrin · Block G

3rd Floor · 20, route de Pré-Bois

Case Postale 1826

1215 Geneva · Switzerland

Tel: (+41 22) 799 4086 / 4088

Fax: (+41 22) 799 4089

E-mail: [email protected]

www.ippph.org

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