Correspondence
antipsychotic drugs are quite different in their receptor binding profiles, it seems obvious that they must differ in efficacy, the question is only how much. We reiterate our interpretation that most efficacy differences are small and usually gradual rather than discrete. The differences in side-effects are overall larger. SL has received honoraria for lectures from Abbvie, AstraZeneca, Bristol-Myers Squibb, ICON, Eli Lilly, Janssen, Johnson & Johnson, Roche, Sanofi-Aventis Lundbeck, and Pfizer; and for consulting or advisory boards from Roche, Eli Lilly, Medavante, BristolMyers Squibb, Alkermes, Janssen, Johnson & Johnson, and Lundbeck. Eli Lilly has provided medication for a study with SL as the primary investigator. JRG was expert witness for Dr Reddys Laboratories and is Chief Investigator on the CEQUEL trial to which GlaxoSmithKline have contributed and supplied investigational drugs. The other authors declare that they have no conflicts of interest.
*Stefan Leucht, Andrea Cipriani, John R Geddes, Georgia Salanti, John M Davis [email protected] Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, 81675 Munich, Germany (SL); Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK (SL, AC, JRG); Department of Medicine and Public Health, Section of Psychiatry, University of Verona, Verona, Italy (AC); Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus Ioannina, Ioannina, Greece (GS); Psychiatric Institute, University of Illinois at Chicago, Chicago, IL, USA (JMD); and Maryland Psychiatric Research Center, Baltimore, MD, USA (JMD) 1
2
3
4
5
6
Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382: 951–62. Mills EJ, Ioannidis JP, Thorlund K, Schunemann HJ, Puhan MA, Guyatt GH. How to use an article reporting a multiple treatment comparison meta-analysis. JAMA 2012; 308: 1246–53. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 2009; 373: 31–41. Davis JM, Chen N, Glick ID. A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry 2003; 60: 553–64. Khin NA, Chen YF, Yang Y, Yang P, Laughren TP. Exploratory analyses of efficacy data from schizophrenia trials in support of new drug applications submitted to the US Food and Drug Administration. J Clin Psychiatry 2012; 73: 856–64. Klein DF, Davis JM. Diagnosis and drug treatment of psychiatric disorders. Baltimore, MD: Williams and Wilkins, 1969.
www.thelancet.com Vol 382 December 7, 2013
Surgical clinical trials— need for international collaboration
New Zealand
Australia Canada
International collaboration in research provides multiple benefits including improving methodological quality, generalisation of the results, and specifically in surgery, greater ease in the recruitment of patients.1 However, collaborations do not seem to be reflected in scientific publications. Between 2007 and 2013, 6957 surgical clinical trials were published in journals indexed in the Web of Science; however, only 1241 (17·8%) were done by international collaborations, although authors were affiliated in 90 different countries. Moreover, collaborative research was done mostly by investigators in Europe and North America (figure). In disciplines other than surgical clinical trials, there appears to be more international collaboration; more than 30% of the publications were done by authors affiliated in at least two countries.2 We note that international collaboration between authors from at least two continents or regions is low with 755 papers (10·9%), and even fewer papers (93 [1·3%]), involved at least three continents. The scarcity of collaboration between North America and Europe and countries in Asia, Oceania, Central or South America, or Africa is concerning, in view of the dependence of these regions on international collaboration for scientific production. For example, North America published 14 papers with countries in Africa; this accounted for 1·1% of the total international collaboration but was 20·9% of the total production of the African countries. There are multiple barriers to collaboration, from technological barriers to institutional policies. Among the strategies for increasing
Austria
Switzerland Japan
UK Sweden
China USA
Brazil
Germany Spain
France
Italy 49* 27*
Netherlands
Belgium
Figure: International collaboration network in surgical clinical trials Only interactions involving more than 19 published studies are shown. *Lines are proportional to 27 and 49 papers in collaboration, respectively.
international collaboration, it is crucial for young researchers to participate in research and publication1,3 to gain experience to boost research and future contacts for the establishment of new research centres in their countries of origin. In South America, this strategy led to the training of highly educated staff which has widened the collaborative networks and had a positive effect on research; experience that could be transferred in the surgical setting. We declare that we have no conflicts of interest.
Charles Huamaní, *Gregorio González-Alcaide [email protected] University of Valencia, Valencia 46020, Spain (GG-A); and Instituto Nacional de Salud, Lima, Peru (CH) 1
Søreide K, Alderson D, Bergenfelz A, et al. Strategies to improve clinical research in surgery through international collaboration. Lancet 2013; 382: 1140–51.
1875
Correspondence
2
3
Huamani C, Gonzalez AG, Curioso WH, Pacheco-Romero J. Scientific production in clinical medicine and international collaboration networks in South American countries. Rev Med Chil 2012; 140: 466–75. Bhangu A, Kolias AG, Pinkney T, Hall NJ, Fitzgerald JE. Surgical research collaboratives in the UK. Lancet 2013; 382: 1091–92.
With a growing burden of surgical procedures and very large numbers of patients, Chinese surgeons should have an important role in seeking consensus on global strategies through participation in international collaboration. 1 However, many obstacles are hindering their enthusiasm for joint studies, including considerable extra workload in clinical research besides a heavy clinical burden, difficulties in participant enrolment due to the deteriorated doctor– patient relationship, language barriers, and limited opportunities to communicate and cooperate with international colleagues. We appeal to health administrators in China for an increased awareness of the importance of collaborative research and for supportive policies. For instance, appropriate assessment of the achievement of these research collaborations is an important issue. The present academic evaluation system in China recognises and rewards the position of first and corresponding authors for published studies, and the contributions of other participants tend to be neglected. Hence, how to encourage the active participation of more surgeons in future international research collaboration is an issue worthy of discussion for health policy makers in China and worldwide. We declare that we have no conflict of interest.
Han Zhang, *Tian Yang, Meng-Chao Wu [email protected] Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China 1
1876
Soreide K, Alderson D, Bergenfelz A, et al. Strategies to improve clinical research in surgery through international collaboration. Lancet 2013; 382: 1140–51.
Surgical clinical trials— need for quantity and quality The implementation of a nationwide surgical trials programme in the UK was the response to the overall need for more clinical trials in surgery.1 Randomised controlled trials (RCTs) represent the gold standard in evaluating effectiveness of novel interventions, hence establishing such a programme is welcomed. However, increasing the number of trials evaluating surgical interventions is necessary but not sufficient. We argue that quality must also be a prerequisite. Indeed, surgical trials with poor methodological quality, principally scarce use of intention-to-treat analysis and allocation concealment, is an area of concern.2 Furthermore, surgical trials associated with poor reporting quality can generate bias when evaluating intervention effectiveness and subsequent suboptimal patient outcomes.3 Along with the challenges described by Becky McCall,1 surgical trials pose further difficulties with respect to blinding, intervention complexity, inconsistent expertise of care providers, and centres’ volume. 4 The Consolidated Standards of Reporting Trials checklist for nonpharmacological interventions (CONSORT NPT)4 was developed to aid reporting of these features, but it has not been enforced by journals. All journals enforcing the mandatory completion of a CONSORT NPT checklist for all RCTs submitted could improve trial reporting, in turn enhancing trial quality. Collaboration between the Royal College of Surgeons and clinical trial units aims to focus on trial methodology, hypothesis development, and mentorship for surgeons. 1 Encouraging education about CONSORT might foster a better trial reporting culture, which could improve trial quality, enabling authentication of best practice.
We declare that we have no conflicts of interest.
*Ankur Khajuria, Riaz Ahmed Agha [email protected] Imperial College London, London SW7 2AZ, UK (AK); and Department of Plastic Surgery, Stoke Mandeville Hospital, Aylesbury, UK (RAA) 1 2
3
4
McCall B. UK implements national programme for surgical trials. Lancet 2013; 382: 1083–84. Agha RA, Camm CF, Edison E, Orgill DP. The methodological quality of randomized controlled trials in plastic surgery needs improvement: a systematic review. J Plast Reconstr Aesthet Surg 2013; 66: 447–52. Agha R, Cooper D, Muir G. The reporting quality of randomised controlled trials in surgery: a systematic review. Int J Surg 2007; 5: 413–22. Boutron I, Moher D, Altman DG, et al. Extending the CONSORT statement to randomized trials of non pharmacologic treatment: explanation and elaboration. Ann Intern Med 2008; 148: 295–309.
Care for patients with grave alcohol use disorders Ryan McCormack and colleagues (Sept 14, p 995)1 pledged that “laws governing involuntary commitment should consider disability associated with grave alcohol use disorders in the same way as other mental illnesses” and urged ”to develop and test innovative policies and practices”.1 This deserves a comment. First, the term “involuntary commitment for patients” seems a voluntary misleading understatement. In fact, involuntary treatment, or assisted treatment, refers to a forced medical treatment undertaken without a person’s consent. Second, this is not “innovative”, but inappropriate policy. Patients gravely disabled by alcohol use disorders reached this advanced state after many years of an evolution characterised by a lack of comprehensive community services and support (as evidenced by the association between forced admissions and poor economic conditions)2 and by inappropriate care. In the USA, among 30 acute and chronic conditions, alcohol dependence ranked the worst for quality of care, www.thelancet.com Vol 382 December 7, 2013
antipsychotic drugs are quite different in their receptor binding profiles, it seems obvious that they must differ in efficacy, the question is only how much. We reiterate our interpretation that most efficacy differences are small and usually gradual rather than discrete. The differences in side-effects are overall larger. SL has received honoraria for lectures from Abbvie, AstraZeneca, Bristol-Myers Squibb, ICON, Eli Lilly, Janssen, Johnson & Johnson, Roche, Sanofi-Aventis Lundbeck, and Pfizer; and for consulting or advisory boards from Roche, Eli Lilly, Medavante, BristolMyers Squibb, Alkermes, Janssen, Johnson & Johnson, and Lundbeck. Eli Lilly has provided medication for a study with SL as the primary investigator. JRG was expert witness for Dr Reddys Laboratories and is Chief Investigator on the CEQUEL trial to which GlaxoSmithKline have contributed and supplied investigational drugs. The other authors declare that they have no conflicts of interest.
*Stefan Leucht, Andrea Cipriani, John R Geddes, Georgia Salanti, John M Davis [email protected] Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, 81675 Munich, Germany (SL); Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK (SL, AC, JRG); Department of Medicine and Public Health, Section of Psychiatry, University of Verona, Verona, Italy (AC); Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus Ioannina, Ioannina, Greece (GS); Psychiatric Institute, University of Illinois at Chicago, Chicago, IL, USA (JMD); and Maryland Psychiatric Research Center, Baltimore, MD, USA (JMD) 1
2
3
4
5
6
Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382: 951–62. Mills EJ, Ioannidis JP, Thorlund K, Schunemann HJ, Puhan MA, Guyatt GH. How to use an article reporting a multiple treatment comparison meta-analysis. JAMA 2012; 308: 1246–53. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 2009; 373: 31–41. Davis JM, Chen N, Glick ID. A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry 2003; 60: 553–64. Khin NA, Chen YF, Yang Y, Yang P, Laughren TP. Exploratory analyses of efficacy data from schizophrenia trials in support of new drug applications submitted to the US Food and Drug Administration. J Clin Psychiatry 2012; 73: 856–64. Klein DF, Davis JM. Diagnosis and drug treatment of psychiatric disorders. Baltimore, MD: Williams and Wilkins, 1969.
www.thelancet.com Vol 382 December 7, 2013
Surgical clinical trials— need for international collaboration
New Zealand
Australia Canada
International collaboration in research provides multiple benefits including improving methodological quality, generalisation of the results, and specifically in surgery, greater ease in the recruitment of patients.1 However, collaborations do not seem to be reflected in scientific publications. Between 2007 and 2013, 6957 surgical clinical trials were published in journals indexed in the Web of Science; however, only 1241 (17·8%) were done by international collaborations, although authors were affiliated in 90 different countries. Moreover, collaborative research was done mostly by investigators in Europe and North America (figure). In disciplines other than surgical clinical trials, there appears to be more international collaboration; more than 30% of the publications were done by authors affiliated in at least two countries.2 We note that international collaboration between authors from at least two continents or regions is low with 755 papers (10·9%), and even fewer papers (93 [1·3%]), involved at least three continents. The scarcity of collaboration between North America and Europe and countries in Asia, Oceania, Central or South America, or Africa is concerning, in view of the dependence of these regions on international collaboration for scientific production. For example, North America published 14 papers with countries in Africa; this accounted for 1·1% of the total international collaboration but was 20·9% of the total production of the African countries. There are multiple barriers to collaboration, from technological barriers to institutional policies. Among the strategies for increasing
Austria
Switzerland Japan
UK Sweden
China USA
Brazil
Germany Spain
France
Italy 49* 27*
Netherlands
Belgium
Figure: International collaboration network in surgical clinical trials Only interactions involving more than 19 published studies are shown. *Lines are proportional to 27 and 49 papers in collaboration, respectively.
international collaboration, it is crucial for young researchers to participate in research and publication1,3 to gain experience to boost research and future contacts for the establishment of new research centres in their countries of origin. In South America, this strategy led to the training of highly educated staff which has widened the collaborative networks and had a positive effect on research; experience that could be transferred in the surgical setting. We declare that we have no conflicts of interest.
Charles Huamaní, *Gregorio González-Alcaide [email protected] University of Valencia, Valencia 46020, Spain (GG-A); and Instituto Nacional de Salud, Lima, Peru (CH) 1
Søreide K, Alderson D, Bergenfelz A, et al. Strategies to improve clinical research in surgery through international collaboration. Lancet 2013; 382: 1140–51.
1875
Correspondence
2
3
Huamani C, Gonzalez AG, Curioso WH, Pacheco-Romero J. Scientific production in clinical medicine and international collaboration networks in South American countries. Rev Med Chil 2012; 140: 466–75. Bhangu A, Kolias AG, Pinkney T, Hall NJ, Fitzgerald JE. Surgical research collaboratives in the UK. Lancet 2013; 382: 1091–92.
With a growing burden of surgical procedures and very large numbers of patients, Chinese surgeons should have an important role in seeking consensus on global strategies through participation in international collaboration. 1 However, many obstacles are hindering their enthusiasm for joint studies, including considerable extra workload in clinical research besides a heavy clinical burden, difficulties in participant enrolment due to the deteriorated doctor– patient relationship, language barriers, and limited opportunities to communicate and cooperate with international colleagues. We appeal to health administrators in China for an increased awareness of the importance of collaborative research and for supportive policies. For instance, appropriate assessment of the achievement of these research collaborations is an important issue. The present academic evaluation system in China recognises and rewards the position of first and corresponding authors for published studies, and the contributions of other participants tend to be neglected. Hence, how to encourage the active participation of more surgeons in future international research collaboration is an issue worthy of discussion for health policy makers in China and worldwide. We declare that we have no conflict of interest.
Han Zhang, *Tian Yang, Meng-Chao Wu [email protected] Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China 1
1876
Soreide K, Alderson D, Bergenfelz A, et al. Strategies to improve clinical research in surgery through international collaboration. Lancet 2013; 382: 1140–51.
Surgical clinical trials— need for quantity and quality The implementation of a nationwide surgical trials programme in the UK was the response to the overall need for more clinical trials in surgery.1 Randomised controlled trials (RCTs) represent the gold standard in evaluating effectiveness of novel interventions, hence establishing such a programme is welcomed. However, increasing the number of trials evaluating surgical interventions is necessary but not sufficient. We argue that quality must also be a prerequisite. Indeed, surgical trials with poor methodological quality, principally scarce use of intention-to-treat analysis and allocation concealment, is an area of concern.2 Furthermore, surgical trials associated with poor reporting quality can generate bias when evaluating intervention effectiveness and subsequent suboptimal patient outcomes.3 Along with the challenges described by Becky McCall,1 surgical trials pose further difficulties with respect to blinding, intervention complexity, inconsistent expertise of care providers, and centres’ volume. 4 The Consolidated Standards of Reporting Trials checklist for nonpharmacological interventions (CONSORT NPT)4 was developed to aid reporting of these features, but it has not been enforced by journals. All journals enforcing the mandatory completion of a CONSORT NPT checklist for all RCTs submitted could improve trial reporting, in turn enhancing trial quality. Collaboration between the Royal College of Surgeons and clinical trial units aims to focus on trial methodology, hypothesis development, and mentorship for surgeons. 1 Encouraging education about CONSORT might foster a better trial reporting culture, which could improve trial quality, enabling authentication of best practice.
We declare that we have no conflicts of interest.
*Ankur Khajuria, Riaz Ahmed Agha [email protected] Imperial College London, London SW7 2AZ, UK (AK); and Department of Plastic Surgery, Stoke Mandeville Hospital, Aylesbury, UK (RAA) 1 2
3
4
McCall B. UK implements national programme for surgical trials. Lancet 2013; 382: 1083–84. Agha RA, Camm CF, Edison E, Orgill DP. The methodological quality of randomized controlled trials in plastic surgery needs improvement: a systematic review. J Plast Reconstr Aesthet Surg 2013; 66: 447–52. Agha R, Cooper D, Muir G. The reporting quality of randomised controlled trials in surgery: a systematic review. Int J Surg 2007; 5: 413–22. Boutron I, Moher D, Altman DG, et al. Extending the CONSORT statement to randomized trials of non pharmacologic treatment: explanation and elaboration. Ann Intern Med 2008; 148: 295–309.
Care for patients with grave alcohol use disorders Ryan McCormack and colleagues (Sept 14, p 995)1 pledged that “laws governing involuntary commitment should consider disability associated with grave alcohol use disorders in the same way as other mental illnesses” and urged ”to develop and test innovative policies and practices”.1 This deserves a comment. First, the term “involuntary commitment for patients” seems a voluntary misleading understatement. In fact, involuntary treatment, or assisted treatment, refers to a forced medical treatment undertaken without a person’s consent. Second, this is not “innovative”, but inappropriate policy. Patients gravely disabled by alcohol use disorders reached this advanced state after many years of an evolution characterised by a lack of comprehensive community services and support (as evidenced by the association between forced admissions and poor economic conditions)2 and by inappropriate care. In the USA, among 30 acute and chronic conditions, alcohol dependence ranked the worst for quality of care, www.thelancet.com Vol 382 December 7, 2013
