Correspondence
2
3
4
5
6
7
8
See Online for appendix
Roberts I, Ker K. How systematic reviews cause research waste. Lancet 2015; 386: 1536. Schulz KF, Grimes DA. Sample size calculations in randomised trials: mandatory and mystical. Lancet 2005; 365: 1348–53. Chalmers I, Nylenna M. A new network to promote evidence-based research. Lancet 2014; 384: 1903–04. Clarke M, Hopewell S, Chalmers I. Clinical trials should begin and end with systematic reviews of relevant evidence: 12 years and waiting. Lancet 2010; 376: 20–21. Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. Lancet 2009; 374: 86–89. Robinson KA, Goodman SN. A systematic examination of the citation of prior research in reports of randomized, controlled trials. Ann Intern Med 2011; 154: 50–55. Nüesch E, Jüni P. Commentary: Which meta-analyses are conclusive? Int J Epidemiol 2009; 38: 298–303.
In their letter, 1 Ian Roberts and Katharine Ker made three assumptions: that small clinical trials are all of poor quality; that all large, multicentre, well funded trials are of exemplary quality; and that meta-analysis cannot ameliorate the low power of small trials. None of these assumptions are documented. Although many clinical trials do have methodological flaws, many do not, and this issue is addressed in systematic reviews with sensitivity analysis. Certainly, the aims of meta-analysis are to achieve increased statistical power and better quality assessment and to obtain a summary statistic. An excellent example of the not infrequent shortcomings of large, well funded trials is the breast cancer screening study 2 published in The Lancet, in which 75% of randomised trials were excluded from meta-analysis because of considerable quality issues. I declare no competing interests.
Richard L Nelson [email protected] School of Public Health, University of Illinois at Chicago, Chicago, IL 60612, USA 1 2
124
Roberts I, Ker K. How systematic reviews cause research waste. Lancet 2015; 386: 1536. Gøtzsche PC, Olsen O. Is screening for breast cancer with mammography justifiable? Lancet 2000; 355: 129–34.
Oseltamivir for influenza Previously1 we called on Joanna Dobson and colleagues2 to make public the protocol for their meta-analysis of randomised controlled trials of oseltamivir. This document could easily be uploaded to a repository such as Dryad, and linked to their research paper. We are alarmed that they neither did this nor explained their reasons for not doing so.3 We are taking this opportunity to reiterate our request. For their work to be taken seriously, there is an imperative to furnish the scientific community with a protocol that pre-dates their analysis. Numerous decisions, from selection of dose for examination, to prespecified and exploratory analysis conducted, definitions of outcomes examined, and statistical methods chosen, cannot be understood and critically assessed without access to the protocol. The Lancet REWARD initiative underscores how important such documents are to sound science.4,5 Furthermore, the Roche-funded Multi-party Group for Advice on Science (MUGAS), which funded Dobson and colleagues’ analysis, held a one day meeting in June 2013 “to develop a statistical analysis plan on Oseltamivir data, both from randomized controlled trials and from observational trials.” The MUGAS press release stated: “This plan will serve as a basis for the post-meeting in depth statistical analysis, eventually to be carried out by MUGAS and MUGAS invited partners”. We call on the authors to release all of these pre-trial documents, and we call on The Lancet to join us in this demand and consider the ramifications of the documents continuing to remain secret. In addition, the conflict of interest disclosure statements for Dobson and colleagues’ original article2 and letter3 are incomplete and need to be corrected. Dobson and Stuart Pocock
declare “no competing interests”, but Dobson’s salary was supported by Roche during the analysis and Pocock told a journalist that he received research funds from Gilead and Genentech.6 Also, Richard Whitley does not inform readers that Gilead Sciences is the patent holder for oseltamivir so readers can evaluate the implications. According to ProPublica and OpenPaymentsData.CMS.gov, Arnold Monto and Whitley also both received money in recent years from companies not listed in The Lancet articles. Finally, despite the fact that all authors are financially linked to the manufacturer or patent holder of oseltamivir, the linked editorial by Heath Kelly and Benjamin Cowling7 inaccurately describes Dobson and colleagues as an “independent research group”. The above inaccuracies all need to be addressed, and we call on The Lancet to help ensure that the record is corrected. See appendix for declaration of interests
*Peter Doshi, Carl Heneghan, Tom Jefferson [email protected] Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, MD, USA (PD); Centre for Evidence-Based Medicine, University of Oxford, UK (CH); and Cochrane Acute Respiratory Infections Group, 00187, Roma, Italy (TJ) 1 2
3
4
5
6
7
Doshi P, Heneghan C, Jefferson T. Oseltamivir for influenza. Lancet 2015; 386: 1134–35. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet 2015; 385: 1729–37. Monto AS, Dobson J, Pocock S, Whitley RJ. Oseltamivir for influenza—Authors’ reply. Lancet 2015; 386: 1135–36. Chan A-W, Song F, Vickers A, et al. Increasing value and reducing waste: addressing inaccessible research. Lancet 2014; 383: 257–66. Ioannidis JPA, Greenland S, Hlatky MA, et al. Increasing value and reducing waste in research design, conduct, and analysis. Lancet 2014; 383: 166–75. Lenzer J. Why aren’t the US Centers for Disease Control and Food and Drug Administration speaking with one voice on flu? BMJ 2015; 350: h658. Kelly H, Cowling BJ. Influenza: the rational use of oseltamivir. Lancet 2015; 385: 1700–02.
www.thelancet.com Vol 387 January 9, 2016
2
3
4
5
6
7
8
See Online for appendix
Roberts I, Ker K. How systematic reviews cause research waste. Lancet 2015; 386: 1536. Schulz KF, Grimes DA. Sample size calculations in randomised trials: mandatory and mystical. Lancet 2005; 365: 1348–53. Chalmers I, Nylenna M. A new network to promote evidence-based research. Lancet 2014; 384: 1903–04. Clarke M, Hopewell S, Chalmers I. Clinical trials should begin and end with systematic reviews of relevant evidence: 12 years and waiting. Lancet 2010; 376: 20–21. Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. Lancet 2009; 374: 86–89. Robinson KA, Goodman SN. A systematic examination of the citation of prior research in reports of randomized, controlled trials. Ann Intern Med 2011; 154: 50–55. Nüesch E, Jüni P. Commentary: Which meta-analyses are conclusive? Int J Epidemiol 2009; 38: 298–303.
In their letter, 1 Ian Roberts and Katharine Ker made three assumptions: that small clinical trials are all of poor quality; that all large, multicentre, well funded trials are of exemplary quality; and that meta-analysis cannot ameliorate the low power of small trials. None of these assumptions are documented. Although many clinical trials do have methodological flaws, many do not, and this issue is addressed in systematic reviews with sensitivity analysis. Certainly, the aims of meta-analysis are to achieve increased statistical power and better quality assessment and to obtain a summary statistic. An excellent example of the not infrequent shortcomings of large, well funded trials is the breast cancer screening study 2 published in The Lancet, in which 75% of randomised trials were excluded from meta-analysis because of considerable quality issues. I declare no competing interests.
Richard L Nelson [email protected] School of Public Health, University of Illinois at Chicago, Chicago, IL 60612, USA 1 2
124
Roberts I, Ker K. How systematic reviews cause research waste. Lancet 2015; 386: 1536. Gøtzsche PC, Olsen O. Is screening for breast cancer with mammography justifiable? Lancet 2000; 355: 129–34.
Oseltamivir for influenza Previously1 we called on Joanna Dobson and colleagues2 to make public the protocol for their meta-analysis of randomised controlled trials of oseltamivir. This document could easily be uploaded to a repository such as Dryad, and linked to their research paper. We are alarmed that they neither did this nor explained their reasons for not doing so.3 We are taking this opportunity to reiterate our request. For their work to be taken seriously, there is an imperative to furnish the scientific community with a protocol that pre-dates their analysis. Numerous decisions, from selection of dose for examination, to prespecified and exploratory analysis conducted, definitions of outcomes examined, and statistical methods chosen, cannot be understood and critically assessed without access to the protocol. The Lancet REWARD initiative underscores how important such documents are to sound science.4,5 Furthermore, the Roche-funded Multi-party Group for Advice on Science (MUGAS), which funded Dobson and colleagues’ analysis, held a one day meeting in June 2013 “to develop a statistical analysis plan on Oseltamivir data, both from randomized controlled trials and from observational trials.” The MUGAS press release stated: “This plan will serve as a basis for the post-meeting in depth statistical analysis, eventually to be carried out by MUGAS and MUGAS invited partners”. We call on the authors to release all of these pre-trial documents, and we call on The Lancet to join us in this demand and consider the ramifications of the documents continuing to remain secret. In addition, the conflict of interest disclosure statements for Dobson and colleagues’ original article2 and letter3 are incomplete and need to be corrected. Dobson and Stuart Pocock
declare “no competing interests”, but Dobson’s salary was supported by Roche during the analysis and Pocock told a journalist that he received research funds from Gilead and Genentech.6 Also, Richard Whitley does not inform readers that Gilead Sciences is the patent holder for oseltamivir so readers can evaluate the implications. According to ProPublica and OpenPaymentsData.CMS.gov, Arnold Monto and Whitley also both received money in recent years from companies not listed in The Lancet articles. Finally, despite the fact that all authors are financially linked to the manufacturer or patent holder of oseltamivir, the linked editorial by Heath Kelly and Benjamin Cowling7 inaccurately describes Dobson and colleagues as an “independent research group”. The above inaccuracies all need to be addressed, and we call on The Lancet to help ensure that the record is corrected. See appendix for declaration of interests
*Peter Doshi, Carl Heneghan, Tom Jefferson [email protected] Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, MD, USA (PD); Centre for Evidence-Based Medicine, University of Oxford, UK (CH); and Cochrane Acute Respiratory Infections Group, 00187, Roma, Italy (TJ) 1 2
3
4
5
6
7
Doshi P, Heneghan C, Jefferson T. Oseltamivir for influenza. Lancet 2015; 386: 1134–35. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet 2015; 385: 1729–37. Monto AS, Dobson J, Pocock S, Whitley RJ. Oseltamivir for influenza—Authors’ reply. Lancet 2015; 386: 1135–36. Chan A-W, Song F, Vickers A, et al. Increasing value and reducing waste: addressing inaccessible research. Lancet 2014; 383: 257–66. Ioannidis JPA, Greenland S, Hlatky MA, et al. Increasing value and reducing waste in research design, conduct, and analysis. Lancet 2014; 383: 166–75. Lenzer J. Why aren’t the US Centers for Disease Control and Food and Drug Administration speaking with one voice on flu? BMJ 2015; 350: h658. Kelly H, Cowling BJ. Influenza: the rational use of oseltamivir. Lancet 2015; 385: 1700–02.
www.thelancet.com Vol 387 January 9, 2016
