- Email: [email protected]
Withholding access to research data – Authors' reply
Correspondence
Devon Brewer and colleagues are correct in pointing out that researchers fear that data they have generated might be manipulated by secondary analysts in ways that contradict their own conclusions. This is precisely why the draft code of conduct to which we refer commits secondary analysts to publish their own detailed methods, and any code used to transform, manipulate, analyse, or interpret datasets. We agree that this sort of transparency in science will increase public trust and reduce the deliberate manipulation of data to score political, financial, or ideological points. We cannot, however, currently agree with Brewer and colleagues’ assertion that only minimal effort is required to make data available to other researchers. To reiterate a central point of our Comment, data management is the weakest part of the research infrastructure in developing countries. This is especially true in large, population-based cohort studies where records are linked across time but for which the definition of variables, measurement standards, and diagnostic criteria might have changed. This situation is difficult even for analysts who know the data very well; the likelihood that incompletely documented data will be misinterpreted or analysed incorrectly by secondary users unfamiliar with such changes is high. If data are analysed inappropriately, the consequences for primary researchers who rely on maintaining the trust of the scientific community and the community in which they work can be dire. Another difficulty is that datasets, especially large longitudinal datasets, are often not fully anonymised. As long as that remains true, it becomes ethically impossible to share the data outside of a team of trusted primary investigators. It is precisely these limitations that we believe must be overcome. Indeed, some of the longitudinal cohort studies to which Brewer and colleagues refer have recently received grants that will be used to document and anonymise www.thelancet.com Vol 375 May 29, 2010
current and past datasets so that data can be made more widely available to bona fide scientists for responsible analysis. We believe strongly that more active sharing of data of public health importance is desirable. Greater investment in data management is key to making it possible. We declare that we have no conflicts of interest.
*Elizabeth Pisani, James Whitworth, Basia Zaba, Carla AbouZahr [email protected] 28 Smalley Close, London N16 7LE, UK (EP); Wellcome Trust, London, UK (JW); Centre for Population Studies, London School of Hygiene and Tropical Medicine, London, UK (BZ); and WHO, Geneva, Switzerland (CAZ)
Antimicrobial drugs for Buruli ulcer In their Article on antimicrobial therapy for early, limited Mycobacterium ulcerans infection in Ghana (Feb 20, p 664),1 Willemien Nienhuis and colleagues conclude that 4 weeks of streptomycin plus rifampicin followed by 4 weeks of rifampicin and clarithromycin has similar efficacy to 8 weeks of streptomycin and rifampicin. Some concerns about the use of clarithromycin in Buruli ulcer need discussing. Treatment failure was higher in the 4-week streptomycin plus 4-week clarithromycin group than in the 8-week streptomycin group. Mycobacterium spp carry many macrolide resistance traits in their chromosomes and can confer high resistance to clarithromycin after exposure to similar classes of drug.2 One study in a mouse model revealed that, when given at a daily dose of 100 mg/kg (equivalent to 1 g per day in human beings), clarithromycin had an obvious bacteriostatic activity: the growth of M ulcerans in mice treated with clarithromycin was significantly delayed compared with that in control mice.3 However, since the activity was not bactericidal, one may question the potential practical value of clarithro-
mycin in the treatment of M ulcerans infection in human beings. The high rate of treatment failure in the 4-week clarithromycin group in Nienhuis and colleagues’ study could reflect this limitation. Moreover, it is now generally accepted that a major protective antigen present in the Bacille Calmette-Guerin (BCG) vaccine is the so-called Ag85 complex which has 84% sequence identity and 91% similarity with M ulcerans Ag85A proteins.4 Logically, then, BCG-vaccinated patients should recover more quickly from Buruli ulcer than non-vaccinated individuals. I have been supported by the Canada Institute of Health Research. I declare that I have no conflicts of interest.
Dewan S Billal [email protected] Centre de Recherche en Infectiologie, RC709 CHUQ, Québec, QC G1V 4G2, Canada 1
2
3
4
Nienhuis WA, Stienstra Y, Thompson WA, et al. Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet 2010; 375: 664–72. Roberts MC. Update on macrolidelincosamide-streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol Lett 2008; 282: 147–59. Dega H, Robert J, Bonnafous P, Jarlier V, Grosset J. Activities of several antimicrobials against Mycobacterium ulcerans infection in mice. Antimicrob Agents Chemother 2000; 44: 2367–72. Tanghe A, Content J, Van Vooren JP, Portaels F, Huygen K. Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer. Infect Immun 2001; 69: 5403–11.
AFP/Getty Images
Authors’ reply
Authors’ reply We appreciate and to a large extent share the concern of Dewan Billal about the role of clarithromycin in the management of Buruli ulcer disease. Although patients who switched to oral treatment with rifampicin and clarithromycin had a statistically similar beneficial response to treatment, assessment of the added effect (if any) of clarithromycin is impossible. Indeed, presently the duration of therapy necessary to switch off mycolactone production and allow the immune system to recover and clear residual bacteria is unclear. Basically, we added clarithromycin to 1873
Devon Brewer and colleagues are correct in pointing out that researchers fear that data they have generated might be manipulated by secondary analysts in ways that contradict their own conclusions. This is precisely why the draft code of conduct to which we refer commits secondary analysts to publish their own detailed methods, and any code used to transform, manipulate, analyse, or interpret datasets. We agree that this sort of transparency in science will increase public trust and reduce the deliberate manipulation of data to score political, financial, or ideological points. We cannot, however, currently agree with Brewer and colleagues’ assertion that only minimal effort is required to make data available to other researchers. To reiterate a central point of our Comment, data management is the weakest part of the research infrastructure in developing countries. This is especially true in large, population-based cohort studies where records are linked across time but for which the definition of variables, measurement standards, and diagnostic criteria might have changed. This situation is difficult even for analysts who know the data very well; the likelihood that incompletely documented data will be misinterpreted or analysed incorrectly by secondary users unfamiliar with such changes is high. If data are analysed inappropriately, the consequences for primary researchers who rely on maintaining the trust of the scientific community and the community in which they work can be dire. Another difficulty is that datasets, especially large longitudinal datasets, are often not fully anonymised. As long as that remains true, it becomes ethically impossible to share the data outside of a team of trusted primary investigators. It is precisely these limitations that we believe must be overcome. Indeed, some of the longitudinal cohort studies to which Brewer and colleagues refer have recently received grants that will be used to document and anonymise www.thelancet.com Vol 375 May 29, 2010
current and past datasets so that data can be made more widely available to bona fide scientists for responsible analysis. We believe strongly that more active sharing of data of public health importance is desirable. Greater investment in data management is key to making it possible. We declare that we have no conflicts of interest.
*Elizabeth Pisani, James Whitworth, Basia Zaba, Carla AbouZahr [email protected] 28 Smalley Close, London N16 7LE, UK (EP); Wellcome Trust, London, UK (JW); Centre for Population Studies, London School of Hygiene and Tropical Medicine, London, UK (BZ); and WHO, Geneva, Switzerland (CAZ)
Antimicrobial drugs for Buruli ulcer In their Article on antimicrobial therapy for early, limited Mycobacterium ulcerans infection in Ghana (Feb 20, p 664),1 Willemien Nienhuis and colleagues conclude that 4 weeks of streptomycin plus rifampicin followed by 4 weeks of rifampicin and clarithromycin has similar efficacy to 8 weeks of streptomycin and rifampicin. Some concerns about the use of clarithromycin in Buruli ulcer need discussing. Treatment failure was higher in the 4-week streptomycin plus 4-week clarithromycin group than in the 8-week streptomycin group. Mycobacterium spp carry many macrolide resistance traits in their chromosomes and can confer high resistance to clarithromycin after exposure to similar classes of drug.2 One study in a mouse model revealed that, when given at a daily dose of 100 mg/kg (equivalent to 1 g per day in human beings), clarithromycin had an obvious bacteriostatic activity: the growth of M ulcerans in mice treated with clarithromycin was significantly delayed compared with that in control mice.3 However, since the activity was not bactericidal, one may question the potential practical value of clarithro-
mycin in the treatment of M ulcerans infection in human beings. The high rate of treatment failure in the 4-week clarithromycin group in Nienhuis and colleagues’ study could reflect this limitation. Moreover, it is now generally accepted that a major protective antigen present in the Bacille Calmette-Guerin (BCG) vaccine is the so-called Ag85 complex which has 84% sequence identity and 91% similarity with M ulcerans Ag85A proteins.4 Logically, then, BCG-vaccinated patients should recover more quickly from Buruli ulcer than non-vaccinated individuals. I have been supported by the Canada Institute of Health Research. I declare that I have no conflicts of interest.
Dewan S Billal [email protected] Centre de Recherche en Infectiologie, RC709 CHUQ, Québec, QC G1V 4G2, Canada 1
2
3
4
Nienhuis WA, Stienstra Y, Thompson WA, et al. Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet 2010; 375: 664–72. Roberts MC. Update on macrolidelincosamide-streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol Lett 2008; 282: 147–59. Dega H, Robert J, Bonnafous P, Jarlier V, Grosset J. Activities of several antimicrobials against Mycobacterium ulcerans infection in mice. Antimicrob Agents Chemother 2000; 44: 2367–72. Tanghe A, Content J, Van Vooren JP, Portaels F, Huygen K. Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer. Infect Immun 2001; 69: 5403–11.
AFP/Getty Images
Authors’ reply
Authors’ reply We appreciate and to a large extent share the concern of Dewan Billal about the role of clarithromycin in the management of Buruli ulcer disease. Although patients who switched to oral treatment with rifampicin and clarithromycin had a statistically similar beneficial response to treatment, assessment of the added effect (if any) of clarithromycin is impossible. Indeed, presently the duration of therapy necessary to switch off mycolactone production and allow the immune system to recover and clear residual bacteria is unclear. Basically, we added clarithromycin to 1873