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Developing country trials present a number of distinct challenges compared with trials in well resourced industrialised settings. They are carried out in vulnerable populations, often in children, often involve infectious diseases and commonly have severe endpoints. Trial capacity lags behind that in developed countries and catching up needs now to be led from the perspective of these sites so recommendations are operational and appropriate. Product development trials are important to register new treatments and vaccines but often do not leave sites with the skills to run their own trials as protocol design, operational planning and data management are conducted by the sponsor. There is also a need for more disease management trials to improve local health outcomes but there is a lack of skills.
Developing countries need to establish a strong platform to lead independent trial programmes; and drive this process. A key difference in wealthier countries is the existence of recognised career paths and training opportunities for those working on trials. Another limitation is the overwhelming number of regulations and guidelines. Researchers consistently say these are confusing and make trials too daunting. More straightforward locally tested and derived interpretations of guidelines, new operational tools as well as untangled regulations could encourage research. There are many initiatives to support researchers in trial conduct yet none specific for developing countries. Skills are needed and they would apply to all diseases, to drug development and disease management trials as well as wider types of clinical research. These skills ensure high ethical standards and quality data. To design and implement trials sites need access to training and resources. All this could be developed, made available and continuously improved through a highly interactive and research led resource.
In 2006 I joined the KEMRI-Wellcome trust programme in Kilifi, Kenya to take up the newly created post of Head of Clinical Trials. The programme had expanded greatly over the previous years and had over 20 trials in operation. These trials varied from small local investigator led studies, to Wellcome Fellowship trials and major projects with partners like the Malaria Vaccine Initiative and the International Aids Vaccine Initiative. I found that there was little overlap between trial teams, a large variance in quality and standards and no system for learning trial skills or career development for trialists. There was a need for sharing best practice, standardising quality systems in terms of ethical conduct and data quality and perhaps above all setting in place systems that enabled all the different types of people working on trials ( nurses, lab technicians, data managers and clinicians etc.) to learn how to be trialists and have career development options. The Malaria Clinical Trials Alliance (part of the INDEPTH group) awarded a 3 year grant that allow us to establish the clinical trial facility (CTF) in Kilifi. The idea was to bring all those working on trials work together as a team and learn from each other.
The experience of setting up the CTF crystallized what I have learnt through working on trials in many different developing countries. What was happening in Kilifi is the reflected in most sites working in resource poor settings with vulnerable populations, in that they lag behind the US and Europe in terms of having trained trialist and real ability to lead and manage trials programme at a site level. I now aim to see if this inequity can be addressed through the Tropical Medicine Clinical Trial Programme by enabling those engaged in research in developing countries at all levels to be instrumental in catching up with the west.
1. Lang TA, Kokwaro GO. Malaria drug and vaccine trials in Africa: obstacles and opportunities. Trans R Soc Trop Med Hyg2008 Jan;102(1):7-10.
2. Lang T, Thuo N, Akech S. Accidental paraffin poisoning in Kenyan children. Trop Med Int Health2008 Jun;13(6):845-7.
3. Lang T, Chilengi R, Noor RA, Ogutu B, Todd JE, Kilama WL, Targett GA. Data safety and monitoring boards for African clinical trials. Trans R Soc Trop Med Hyg2008 Dec;102(12):1189-94.
4. Hawkridge T, Scriba TJ, Gelderbloem S, Smit E, Tameris M, Moyo S, Lang T, Veldsman A, Hatherill M, Merwe L, Fletcher HA, Mahomed H, Hill AV, Hanekom WA, Hussey GD, McShane H. Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. J Infect Dis2008 Aug 15;198(4):544-52.
5. Fegan GW, Lang TA. Could an open-source clinical trial data-management system be what we have all been looking for? PLoS Med2008 Mar 4;5(3):e6.
6. Bejon P, Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Mshamu S, Lang T, Gould J, Dubois MC, Demoitie MA, Stallaert JF, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, von Seidlein L. Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med2008 Dec 11;359(24):2521-32.
7. Imoukhuede EB, Andrews L, Milligan P, Berthoud T, Bojang K, Nwakanma D, Ismaili J, Buckee C, Njie F, Keita S, Sowe M, Lang T, Gilbert SC, Greenwood BM, Hill AV. Low-level malaria infections detected by a sensitive polymerase chain reaction assay and use of this technique in the evaluation of malaria vaccines in an endemic area. Am J Trop Med Hyg2007 Mar;76(3):486-93.
8. Bejon P, Ogada E, Mwangi T, Milligan P, Lang T, Fegan G, Gilbert SC, Peshu N, Marsh K, Hill AV. Extended follow-up following a phase 2b randomized trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya. PLoS ONE2007;2(1):e707.
9. Bejon P, Mwacharo J, Kai O, Todryk S, Keating S, Lowe B, Lang T, Mwangi TW, Gilbert SC, Peshu N, Marsh K, Hill AV. The induction and persistence of T cell IFN-gamma responses after vaccination or natural exposure is suppressed by Plasmodium falciparum.J Immunol2007 Sep 15;179(6):4193-201.
10. Lang T, Hughes D, Kanyok T, Kengeya-Kayondo J, Marsh V, Haaland A, Pirmohamed M, Winstanley P. Beyond registration--measuring the public-health potential of new treatments for malaria in Africa. Lancet Infect Dis2006 Jan;6(1):46-52.
11. Imoukhuede EB, Berthoud T, Milligan P, Bojang K, Ismaili J, Keating S, Nwakanma D, Keita S, Njie F, Sowe M, Todryk S, Laidlaw SM, Skinner MA, Lang T, Gilbert S, Greenwood BM, Hill AV. Safety and immunogenicity of the malaria candidate vaccines FP9 CS and MVA CS in adult Gambian men. Vaccine2006 Oct 30;24(42-43):6526-33.
12. Bejon P, Peshu N, Gilbert SC, Lowe BS, Molyneux CS, Forsdyke J, Lang T, Hill AV, Marsh K. Safety profile of the viral vectors of attenuated fowlpox strain FP9 and modified vaccinia virus Ankara recombinant for either of 2 preerythrocytic malaria antigens, ME-TRAP or the circumsporozoite protein, in children and adults in Kenya. Clin Infect Dis2006 Apr 15;42(8):1102-10.
13. Bejon P, Mwacharo J, Kai OK, Todryk S, Keating S, Lang T, Gilbert SC, Peshu N, Marsh K, Hill AV. Immunogenicity of the candidate malaria vaccines FP9 and modified vaccinia virus Ankara encoding the pre-erythrocytic antigen ME-TRAP in 1-6 year old children in a malaria endemic area. Vaccine2006 May 29;24(22):4709-15.
14. Bejon P, Mwacharo J, Kai O, Mwangi T, Milligan P, Todryk S, Keating S, Lang T, Lowe B, Gikonyo C, Molyneux C, Fegan G, Gilbert SC, Peshu N, Marsh K, Hill AV. A phase 2b randomised trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya. PLoS Clin Trials2006;1(6):e29.
15. Bejon P, Keating S, Mwacharo J, Kai OK, Dunachie S, Walther M, Berthoud T, Lang T, Epstein J, Carucci D, Moris P, Cohen J, Gilbert SC, Peshu N, Marsh K, Hill AV. Early gamma interferon and interleukin-2 responses to vaccination predict the late resting memory in malaria-naive and malaria-exposed individuals. Infect Immun2006 Nov;74(11):6331-8.
16. Bejon P, Kai OK, Mwacharo J, Keating S, Lang T, Gilbert SC, Peshu N, Marsh K, Hill AV. Alternating vector immunizations encoding pre-erythrocytic malaria antigens enhance memory responses in a malaria endemic area. Eur J Immunol2006 Aug;36(8):2264-72.
17. Lang T, Hill AV, McShane H, Shah R, Towse A, Pritchard C, Garau M. New TB vaccine granted orphan drug status. BMJ2005 Dec 17;331(7530):1476.
18. Alloueche A, Bailey W, Barton S, Bwika J, Chimpeni P, Falade CO, Fehintola FA, Horton J, Jaffar S, Kanyok T, Kremsner PG, Kublin JG, Lang T, Missinou MA, Mkandala C, Oduola AM, Premji Z, Robertson L, Sowunmi A, Ward SA, Winstanley PA. Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial. Lancet2004 Jun 5;363(9424):1843-8.
19 Lang T, Greenwood B. The development of Lapdap, an affordable new treatment for malaria. Lancet Infect Dis2003 Mar;3(3):162-8.