Eligibility criteria and outcome measures adopted in clinical trials of treatments of cutaneous leishmaniasis: systematic literature review covering the period 1991–2015

Abstract

Abstractobjective To document the sources of heterogeneity in outcomes and shortcomings in trial designs reported by previous systematic reviews.methods Systematic review of clinical trials of CL treatments published since 1991, to assess and compare eligibility criteria and outcome measures in trials (any type of treatment) of CL (any form) reported before and after the publication of the CONSORT statement.results We identified 106 eligible trials published between 1991 and 2015, 74% after the 2001 CONSORT statement; 58% (n = 63) were on Old-World CL and 37% (n = 40) in New-World CL; overall, 11 531 patients enrolled in 243 treatment groups on 30 different treatments. Both requirements and definitions for eligibility and outcome criteria varied. Compliance with CONSORT requirements increased for studies published after the 2010 update. As for entry criteria, 94% of studies had a requirement for sex (74% of those enrolling also women excluded those who were pregnant or lactating), 69% for age (variable age ranges), 99% parasitological confirmation, 43% prior duration of illness (14% excluded cases with previous episodes), 46% defined the number, 28% the size and 13% the type of lesions (27% with restrictions as to their anatomical location). Follow-up ranged 1-24 months, with 14% and 91% of studies, respectively, having defined initial and final cure.conclusions This review documents changes in reporting before and after the publication of the CONSORT statement. Lack of standardisation, compounded with the small number of trials relative to the magnitude of the disease in its multiple forms, and with the range of treatments tested explains why evidence to inform treatment guidelines is generally weak for CL. Adopting standardised methodologies will improve the quality and consistency of clinical trials, and ultimately yield better treatments for CL.

Intradermal Synthetic DNA Vaccination Generates Leishmania -Specific T Cells in the Skin and Protection against Leishmania major

“…There are a number of barriers that bar access to the few treatments available for leishmaniasis, including high costs, quality control issues, low production capacities, and physical geography (14,15). However, evidence that people who recover from clinical disease are generally protected from future infection suggests that a vaccine approach is feasible, and there are currently a large number of potential vaccines being tested in both experimental animal models and clinical trials (16)(17)(18). However, none of these options are currently available for human leishmaniasis.…”

Patients’ preferences of cutaneous leishmaniasis treatment outcomes: Findings from an international qualitative study

“…These relate to their personal health and wellbeing as well as their social and socioeconomic context, and comprise the domains Lesion appearance, Side effects, Recurrence, Getting rid of the parasite, Scar formation, Daily activities, Pain and Sequelae. Many of the reported outcomes are generally not reflected in trials conducted to date, which focus mostly on outcomes looking at lesion and infection indicators (such as absence of an active lesion, complete re-epithelisation, parasitological cure, no appearance of new lesions and/or reversible hypopigmentation) [3][4][5][6][7][8].…”

“…At present, there is no treatment which is effective, safe and easy to administer against all clinical forms of the disease. This is largely due to the lack of investments in drug development for a disease that affects essentially impoverished populations, it is also contributed to by weaknesses in the design and conduct of clinical trials for CL interventions which render meta-analysis of results and evidence-based recommendations difficult [2][3][4][5][6][7][8][9].…”

“…TDR had the dual role of being the funder and having an active role in the planning, execution and interpretation of the research as well as in strengthening the researchers' capacity in qualitative research, in line with its mission to support research and capacity for research. parasitological endpoints, but rarely report outcomes affecting patients' quality of life (QoL), or factor in patients' needs in the design phase: A recent systematic review on outcomes included in trials for CL interventions [7] found that nearly all (100% and 86.35% of the studies which included initial and definitive cure, respectively) used complete re-epithelisation of the ulcer as the definition of 'cure'. Additional criteria that were variably present included: absence of active lesion, no relapse, negative parasitological test, clinical improvement, no appearance of new lesions, and/or reversible hypopigmentation.…”

Design, conduct, analysis, and reporting of therapeutic efficacy studies in Visceral Leishmaniasis: A systematic review of published reports, 2000-2021

“…A thorough review on methodological aspects of design, conduct, analysis, and reporting of VL clinical therapeutic efficacy studies is currently lacking. Such review has been carried out in the context of cutaneous leishmaniasis [4][5][6][7] , leading to preparation of a guidance document on optimal approaches for design, conduct, analysis and reporting of CL studies 7 .…”