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Review
. 2012 Oct 22:345:e6512.
doi: 10.1136/bmj.e6512.

Neglected tropical diseases: survey and geometry of randomised evidence

Shanthi Kappagoda  1 , John P A Ioannidis
Affiliations
Review

Neglected tropical diseases: survey and geometry of randomised evidence

Shanthi Kappagoda et al. BMJ. .

Abstract

Objective: To assess the quantity and distribution of evidence from randomised controlled trials for the treatment of the major neglected tropical diseases and to identify gaps in the evidence with network analysis.

Design: Systematic review and network analysis.

Data sources: Cochrane Central Register of Controlled Trials and PubMed from inception to 31 August 2011.

Study selection: Randomised controlled trials that examined treatment of 16 neglected tropical diseases or complications thereof published in English, French, Spanish, Portuguese, German, or Dutch.

Results: We identified 971 eligible randomised trials. Leishmaniasis (184 trials, 23,039 participants) and geohelminth infections; 160 trials, 46,887 participants) were the most studied, while dracunculiasis (nine trials, 798 participants) and Buruli ulcer (five trials, 337 participants) were least studied. Relative to its global burden of disease, lymphatic filariasis had the fewest trials and participants. Only 11% of trials were industry funded. Either a single trial or trials with fewer than 100 participants comprised the randomised evidence for first or second line treatments for Buruli ulcer, human African trypanosomiasis, American trypanosomiasis, cysticercosis, rabies, echinococcosis, New World cutaneous leishmaniasis, and each of the foodborne trematode infections. Among the 10 disease categories with more than 40 trials, five lacked sufficient head to head comparisons between first or second line treatments.

Conclusions: There is considerable variation in the amount of evidence from randomised controlled trials for each of the 16 major neglected tropical diseases. Even in diseases with substantial evidence, such as leishmaniasis and geohelminth infections, some recommended treatments have limited supporting data and lack head to head comparisons.

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Conflict of interest statement

Competing interests: Both authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Schematic of literature search
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Fig 2 Total sample size and number of clinical trials over time
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Fig 3 Network diagrams for diseases with more than 40 randomised controlled trials. Node size is proportional to total sample size and line thickness is proportional to number of comparisons. Scale of nodes is different between different networks; see appendix table 3 for exact information on number of participants on each regimen. ABLC=amphotericin B lipid complex; ACT=artesunate combination treatment (includes artesunate+sulfalene, artesunate+mefloquine, artesunate+sulfadoxine-pyrimethamine, artesunate+sulfamethoxypyrazine-pyrimethamine, artesunate-amodiaquine and artesunate+praziquantel); ALB=albendazole; AM=antigen marianum; Azithro=azithromycin; Clarithro=clarithromycin; CLO=clofazimine; DAP=dapsone; DEC=diethylcarbamazine; Doxy=doxycycline; FLUB=flubendazole; GM-CSF=granulocyte-macrophage colony-stimulating factor; IFN=interferon; INH=isoniazid; Itra=itraconazole; IVM=ivermectin; LEV=levamisole; MEB=mebendazole; Metro=metronidazole; MINO=minocycline; MVT=multivitamin; NIC=nicotinamide; NT=no treatment; OxPyrPam=oxantel-pyrantel pamoate; PAs=pentavalent antimonials; PIP=piperazine; PRO=prothionamide; PyrPam=pyrantel pamoate; PZA=pyrazinamide; PZQ=praziquantel; RIF=rifampin; RIF+CLO+DAP=rifampin, clofazimine, and dapsone; SDM=sulfadimethoxine; SMP=sulfamethoxypyridazine; SODM=sulforthodimethoxine; TCE=tetrachloroethylene; TAC=thiacetazone; Topical AG=topical aminoglycoside
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