DOI: 10.1089/end.2015.1503 CROES COUNCIL Chairman Jean de la Rosette, M.D. Amsterdam (The Netherlands) Adrian Joyce, M.S. Leeds (UK)
JOIN THE PREMIER RESEARCH OFFICE IN THE FIELD OF ENDOUROLOGY
Stavros Gravas, M.D. Larissa (Greece) Jorge Gutierrez-Aceves, M.D. Winston Salem (USA) Dean Assimos, M.D. Birmingham (USA) Ying-Hao Sun, M.D. Shanghai (China) Tadashi Matsuda, M.D. Osaka ( Japan)
Take part in publications and presentations that offer exposure to your institution Become a member of the global research network of Endourologists Be recognized as a centre of excellence in the field of Endourology
TREASURER John Denstedt, M.D. London (Canada)
EXECUTIVE DIRECTOR Sonja van Rees Vellinga Amsterdam (The Netherlands) [email protected]
109
CLINICAL RESEARCH OFFICE OF THE ENDOUROLOGICAL SOCIETY GLOBAL REGISTRIES: A RELIABLE PLATFORM FOR ROBUST EVIDENCE IN ENDOUROLOGY Charalampos Mamoulakis Background The Clinical Research Office of the Endourological Society (CROES) has been facilitating global clinical research in endourology for more than 6 years. Fulfilling its objectives (promote/support international research, create a global network, provide adequate infrastructure to support/conduct studies, serve as a platform for technologic development in partnership with industry),1 CROES has coordinated several qualitative (survey-based) studies and a number of prospective quantitative (global registry-based) studies to date, including the Global Percutaneous Nephrolithotomy (PCNL) Study, the Global GreenLightÔ Laser Study, the Global Renal Mass Study, the Global Ureterorenoscopy Study, and the first randomized controlled trial (RCT), namely the Global Narrow Band Imaging (NBI) Study.2 Quality of CROES global patient registries Patient registry is an organized system that uses observational study methods to collect uniform data to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and serves one or more predetermined scientific/clinical purposes.3 The development of a high-quality patient registry is demanding, but the benefits of such a hard task have long been recognized. Such registries must include data on all consecutive cases, make use of standardized definitions of conditions/outcomes, ensure data completeness/accuracy, and include data on all known patient characteristics that may potentially affect the outcomes.1 Concretely, for the planning and creation of high quality registries, the following should apply3: (1) Data are collected in a naturalistic manner—that is, patient management is determined by caregivers and patients together and not by the registry protocol; (2) the registry is designed to fulfill specific purposes defined before data collection/analysis; (3) the registry captures data elements with specific/consistent definitions; (4) data are collected in a uniform manner for each patient; (5) data collected are derived from/reflect the clinical status of the patient; and (6) data are collected specifically for the purpose of the registry rather than inferred from sources created for another purpose (administrative, billing, pharmacy databases, etc.). CROES fully endorses these recommendations aiming to conduct studies according to highest standards of ethics and quality. Its structure facilitates the necessary conditions that guaranty reliable/ scientifically credible study conduction by focusing on particular steps that ensure highest quality of its patient registries. To safeguard that CROES registries are conducted within a reliable platform able to provide robust evidence in endourology, an audit committee is in place.4 This mechanism most of the time is absent from other retrospective multicenter data sets or even from prospective multicenter 110
studies being undertaken currently. Consequently, the CROES network can truly claim to be able to provide robust evidence from their global registries.
Registry-based studies vs RCTs In the era of evidence-based urology, the highest level of evidence (LoE) is demanded. Such evidence is typically derived from well-designed, conducted, and reported (international multicenter) RCTs and high-quality RCT-based meta-analyses. It is well recognized, though, that high-quality surgical RCTs are scarce in several fields, with a majority of urologic studies providing a low LoE not well suited to guiding clinical decisions because of barriers to high-quality surgical research inevitably jeopardizing the validity of many RCTs.5 This fact often leads to a compromise by accepting ‘‘the best available evidence’’ in many cases,5–7 and potential solutions have already started to be implemented.8 Registry-based studies and RCTs have important and complementary roles in evaluating patient outcomes.9 Ideally, registries consist of data collected in a comprehensive manner, potentially producing generalizable results to a wide range of patients; they evaluate actual care (not assigned, determined, or recommended by a protocol), reflecting better real-world practice; they offer the ability to evaluate outcomes when RCTs are difficult, impractical, or not ethically acceptable to conduct (such as often in surgery), or when very long-term outcomes are desired.3 Furthermore, registries can also facilitate the conduct of RCTs by retrospectively identifying very large numbers of potential subjects for eligibility screening and enrollment in RCTs. This matching can lead to more timely recruitment and help solve a major problem in conducting clinical trials.10 Registries observing real-world clinical practice may collect all the information to assess outcomes in a generalizable way, but interpretation necessitates analytic methodology geared to address potential bias sources that challenge observational studies, while data interpretation necessitates internal validity checks and sometimes uses of external data sources to validate key assumptions.3 Patient registries and RCTs should be considered tools for evidence development, each with its own advantages and limitations.11 A question that arises, however, is where to place registry-based studies within the evidence hierarchy. Even the most rigorously conducted registries, such as prospective observational studies, are traditionally placed below RCTs in some commonly used hierarchies, and at an equal position in others.12–14 Debate continues regarding traditional methods of grading LoE.11,15,16 Beyond evidence hierarchy debate, evidence users should comprehend the value of registries for providing complementary information that can extend the results of RCTs to populations not studied in those trials, for showing real-world effects of treatments outside of the research setting and potentially in large subsets of affected patients, and for providing long-term follow-up when such data are not available from clinical trials.3
Novel CROES global patient registries Consistent with its mission and vision, CROES has recently launched the coordination of two new projects: (1) Registry of irreversible electroporation for the ablation of prostate cancer with the use of Nanoknife (IRE Nanoknife) and (2) registry for treatment of upper-tract urothelial cancer (UTUC). IRE Nanoknife is a multicenter international registry (prospective observational study) to evaluate treatment of patients with prostate cancer in terms of recurrence and functional outcomes/safety. Data will be recorded for 5 years from consecutive patients undergoing treatment with IRE NanoknifeÒ (AngioDynamics) for ablating prostate cancer, with a 5-year follow-up. The aim is to assess recurrence after 1 and 5 years, to determine baseline patient characteristics, and to collect information on possible differences in IRE treatment among centers. UTUC is a multicenter international registry (prospective observational study) to evaluate the treatment of UTUC in terms of incidence, indications, treatment types, and outcomes. Data from consecutive patients undergoing treatment for UTUC will be recorded. Main study parameters/end 111
points are overall and cancer-specific survival at 1 year after diagnosis after different kinds of treatment. Follow-up will be as long as 5 years. References
1. de la Rosette J. A platform for global endourological research. J Endourol 2009;23:1551–1553. 2. Opondo D, de la Rosette J. CROES survey-based studies: The role of expert opinion in endourologic research. J Endourol 2013;27:118–119. 3. Gliklich R, Dreyer N, Leavy M, eds. Registries for Evaluating Patient Outcomes: A User’s Guide. 3rd ed. (Prepared by the Outcome DEcIDE Center [Outcome Sciences, Inc., a Quintiles company] under Contract No. 290 2005 00351 TO7.) AHRQ Publication No. 13(14)-EHC111. Rockville, MD: Agency for Healthcare Research and Quality. April 2014. Available at: http://www.effectivehealthcare.ahrq.gov/registries-guide-3.cfm Accessed: January 5, 2015. 4. Preminger GM, Alken P, Habuchi T, et al. The clinical research office of the endourological society audit committee. J Endourol 2011;25:1811–1813. 5. Mamoulakis C. A plea for higher-quality data for GreenLight laser technology in the context of surgical benign prostatic obstruction trials: The GOLIATH study—fact or fiction in the era of evidence-based urology? Eur Urol 2014;65:943–945. 6. Mamoulakis C, Ubbink DT, de la Rosette JJ. Bipolar versus monopolar transurethral resection of the prostate: A systematic review and meta-analysis of randomized controlled trials. Eur Urol 2009;56:798–809. 7. Mamoulakis C, Schulze M, Skolarikos A, et al. Reply from Authors re: Alexander Bachmann, Gordon H. Muir, Stephen F. Wyler, Malte Rieken. Surgical benign prostatic hyperplasia trials: The future is now! Eur Urol. 2013;63:677–679. Best available evidence in 2012 on bipolar versus monopolar transurethral resection of the prostate for benign prostatic obstruction: It’s about time to decide! Eur Urol. 2013;63:677–680. 8. Surgical research: The reality and the IDEAL. Lancet 2009;374:1037. 9. Dreyer NA, Garner S. Registries for robust evidence. JAMA 2009;302:790–791. 10. Tan MH, Thomas M, MacEachern MP. Using registries to recruit subjects for clinical trials. Contemp Clin Trials 2014. Epub ahead of print. Doi: 10.1016/j.cct.2014.12.012. 11. Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 2000;342:1887–1892. 12. Guyatt GH, Sackett DL, Sinclair JC, et al. Users’ guides to the medical literature. IX. A method for grading health care recommendations. Evidence- Based Medicine Working Group. JAMA 1995;274:1800–1804. 13. Agency for Healthcare Research and Quality. Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews. Version 1.0 [Draft posted Oct. 2007]. Rockville, MD. Available at: http:// effectivehealthcare.ahrq.gov/repFiles/ 2007_10Dra ftMethodsGuide.pdf Accessed: August 14, 2012. 14. Vandenbroucke JP. Observational research, randomised trials, and two views of medical science. PLoS Med 2008;5:e67. 15. Atkins D, Eccles M, Flottorp S, et al. Systems for grading the quality of evidence and the strength of recommendations I: Critical appraisal of existing approaches The GRADE Working Group. BMC Health Serv Res 2004;4:38. 16. Rawlins M. De Testimonio: On the evidence for decisions about the use of therapeutic interventions. Clin Med 2008;8: 579–588.
The Global Ureteroscopy Study, Global GreenLightÔ Laser Study, and the Global Renal Mass Study were closed in 2012. The first five papers on URS and the first one on the Renal Mass Study have been published. The first two articles of the Global GreenLightÔ Laser study are under review. The randomized study on Narrow Band Imaging vs White Light Imaging closed in 2013.The first results are being analyzed. Ongoing project: The Irreversible Electroporation Study study for focal therapy including a pilot study, a randomized controlled trial, and a Registry. New project: The randomized study on SPIES vs White Light Imaging. New project: The Global Upper Tract-Transitional-Cell Carcinoma Study. For further information please visit: www.croesoffice.org or contact the executive director of CROES, Mrs. Sonja van Rees Vellinga ([email protected]).
112
Copyright of Journal of Endourology is the property of Mary Ann Liebert, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
JOIN THE PREMIER RESEARCH OFFICE IN THE FIELD OF ENDOUROLOGY
Stavros Gravas, M.D. Larissa (Greece) Jorge Gutierrez-Aceves, M.D. Winston Salem (USA) Dean Assimos, M.D. Birmingham (USA) Ying-Hao Sun, M.D. Shanghai (China) Tadashi Matsuda, M.D. Osaka ( Japan)
Take part in publications and presentations that offer exposure to your institution Become a member of the global research network of Endourologists Be recognized as a centre of excellence in the field of Endourology
TREASURER John Denstedt, M.D. London (Canada)
EXECUTIVE DIRECTOR Sonja van Rees Vellinga Amsterdam (The Netherlands) [email protected]
109
CLINICAL RESEARCH OFFICE OF THE ENDOUROLOGICAL SOCIETY GLOBAL REGISTRIES: A RELIABLE PLATFORM FOR ROBUST EVIDENCE IN ENDOUROLOGY Charalampos Mamoulakis Background The Clinical Research Office of the Endourological Society (CROES) has been facilitating global clinical research in endourology for more than 6 years. Fulfilling its objectives (promote/support international research, create a global network, provide adequate infrastructure to support/conduct studies, serve as a platform for technologic development in partnership with industry),1 CROES has coordinated several qualitative (survey-based) studies and a number of prospective quantitative (global registry-based) studies to date, including the Global Percutaneous Nephrolithotomy (PCNL) Study, the Global GreenLightÔ Laser Study, the Global Renal Mass Study, the Global Ureterorenoscopy Study, and the first randomized controlled trial (RCT), namely the Global Narrow Band Imaging (NBI) Study.2 Quality of CROES global patient registries Patient registry is an organized system that uses observational study methods to collect uniform data to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and serves one or more predetermined scientific/clinical purposes.3 The development of a high-quality patient registry is demanding, but the benefits of such a hard task have long been recognized. Such registries must include data on all consecutive cases, make use of standardized definitions of conditions/outcomes, ensure data completeness/accuracy, and include data on all known patient characteristics that may potentially affect the outcomes.1 Concretely, for the planning and creation of high quality registries, the following should apply3: (1) Data are collected in a naturalistic manner—that is, patient management is determined by caregivers and patients together and not by the registry protocol; (2) the registry is designed to fulfill specific purposes defined before data collection/analysis; (3) the registry captures data elements with specific/consistent definitions; (4) data are collected in a uniform manner for each patient; (5) data collected are derived from/reflect the clinical status of the patient; and (6) data are collected specifically for the purpose of the registry rather than inferred from sources created for another purpose (administrative, billing, pharmacy databases, etc.). CROES fully endorses these recommendations aiming to conduct studies according to highest standards of ethics and quality. Its structure facilitates the necessary conditions that guaranty reliable/ scientifically credible study conduction by focusing on particular steps that ensure highest quality of its patient registries. To safeguard that CROES registries are conducted within a reliable platform able to provide robust evidence in endourology, an audit committee is in place.4 This mechanism most of the time is absent from other retrospective multicenter data sets or even from prospective multicenter 110
studies being undertaken currently. Consequently, the CROES network can truly claim to be able to provide robust evidence from their global registries.
Registry-based studies vs RCTs In the era of evidence-based urology, the highest level of evidence (LoE) is demanded. Such evidence is typically derived from well-designed, conducted, and reported (international multicenter) RCTs and high-quality RCT-based meta-analyses. It is well recognized, though, that high-quality surgical RCTs are scarce in several fields, with a majority of urologic studies providing a low LoE not well suited to guiding clinical decisions because of barriers to high-quality surgical research inevitably jeopardizing the validity of many RCTs.5 This fact often leads to a compromise by accepting ‘‘the best available evidence’’ in many cases,5–7 and potential solutions have already started to be implemented.8 Registry-based studies and RCTs have important and complementary roles in evaluating patient outcomes.9 Ideally, registries consist of data collected in a comprehensive manner, potentially producing generalizable results to a wide range of patients; they evaluate actual care (not assigned, determined, or recommended by a protocol), reflecting better real-world practice; they offer the ability to evaluate outcomes when RCTs are difficult, impractical, or not ethically acceptable to conduct (such as often in surgery), or when very long-term outcomes are desired.3 Furthermore, registries can also facilitate the conduct of RCTs by retrospectively identifying very large numbers of potential subjects for eligibility screening and enrollment in RCTs. This matching can lead to more timely recruitment and help solve a major problem in conducting clinical trials.10 Registries observing real-world clinical practice may collect all the information to assess outcomes in a generalizable way, but interpretation necessitates analytic methodology geared to address potential bias sources that challenge observational studies, while data interpretation necessitates internal validity checks and sometimes uses of external data sources to validate key assumptions.3 Patient registries and RCTs should be considered tools for evidence development, each with its own advantages and limitations.11 A question that arises, however, is where to place registry-based studies within the evidence hierarchy. Even the most rigorously conducted registries, such as prospective observational studies, are traditionally placed below RCTs in some commonly used hierarchies, and at an equal position in others.12–14 Debate continues regarding traditional methods of grading LoE.11,15,16 Beyond evidence hierarchy debate, evidence users should comprehend the value of registries for providing complementary information that can extend the results of RCTs to populations not studied in those trials, for showing real-world effects of treatments outside of the research setting and potentially in large subsets of affected patients, and for providing long-term follow-up when such data are not available from clinical trials.3
Novel CROES global patient registries Consistent with its mission and vision, CROES has recently launched the coordination of two new projects: (1) Registry of irreversible electroporation for the ablation of prostate cancer with the use of Nanoknife (IRE Nanoknife) and (2) registry for treatment of upper-tract urothelial cancer (UTUC). IRE Nanoknife is a multicenter international registry (prospective observational study) to evaluate treatment of patients with prostate cancer in terms of recurrence and functional outcomes/safety. Data will be recorded for 5 years from consecutive patients undergoing treatment with IRE NanoknifeÒ (AngioDynamics) for ablating prostate cancer, with a 5-year follow-up. The aim is to assess recurrence after 1 and 5 years, to determine baseline patient characteristics, and to collect information on possible differences in IRE treatment among centers. UTUC is a multicenter international registry (prospective observational study) to evaluate the treatment of UTUC in terms of incidence, indications, treatment types, and outcomes. Data from consecutive patients undergoing treatment for UTUC will be recorded. Main study parameters/end 111
points are overall and cancer-specific survival at 1 year after diagnosis after different kinds of treatment. Follow-up will be as long as 5 years. References
1. de la Rosette J. A platform for global endourological research. J Endourol 2009;23:1551–1553. 2. Opondo D, de la Rosette J. CROES survey-based studies: The role of expert opinion in endourologic research. J Endourol 2013;27:118–119. 3. Gliklich R, Dreyer N, Leavy M, eds. Registries for Evaluating Patient Outcomes: A User’s Guide. 3rd ed. (Prepared by the Outcome DEcIDE Center [Outcome Sciences, Inc., a Quintiles company] under Contract No. 290 2005 00351 TO7.) AHRQ Publication No. 13(14)-EHC111. Rockville, MD: Agency for Healthcare Research and Quality. April 2014. Available at: http://www.effectivehealthcare.ahrq.gov/registries-guide-3.cfm Accessed: January 5, 2015. 4. Preminger GM, Alken P, Habuchi T, et al. The clinical research office of the endourological society audit committee. J Endourol 2011;25:1811–1813. 5. Mamoulakis C. A plea for higher-quality data for GreenLight laser technology in the context of surgical benign prostatic obstruction trials: The GOLIATH study—fact or fiction in the era of evidence-based urology? Eur Urol 2014;65:943–945. 6. Mamoulakis C, Ubbink DT, de la Rosette JJ. Bipolar versus monopolar transurethral resection of the prostate: A systematic review and meta-analysis of randomized controlled trials. Eur Urol 2009;56:798–809. 7. Mamoulakis C, Schulze M, Skolarikos A, et al. Reply from Authors re: Alexander Bachmann, Gordon H. Muir, Stephen F. Wyler, Malte Rieken. Surgical benign prostatic hyperplasia trials: The future is now! Eur Urol. 2013;63:677–679. Best available evidence in 2012 on bipolar versus monopolar transurethral resection of the prostate for benign prostatic obstruction: It’s about time to decide! Eur Urol. 2013;63:677–680. 8. Surgical research: The reality and the IDEAL. Lancet 2009;374:1037. 9. Dreyer NA, Garner S. Registries for robust evidence. JAMA 2009;302:790–791. 10. Tan MH, Thomas M, MacEachern MP. Using registries to recruit subjects for clinical trials. Contemp Clin Trials 2014. Epub ahead of print. Doi: 10.1016/j.cct.2014.12.012. 11. Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 2000;342:1887–1892. 12. Guyatt GH, Sackett DL, Sinclair JC, et al. Users’ guides to the medical literature. IX. A method for grading health care recommendations. Evidence- Based Medicine Working Group. JAMA 1995;274:1800–1804. 13. Agency for Healthcare Research and Quality. Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews. Version 1.0 [Draft posted Oct. 2007]. Rockville, MD. Available at: http:// effectivehealthcare.ahrq.gov/repFiles/ 2007_10Dra ftMethodsGuide.pdf Accessed: August 14, 2012. 14. Vandenbroucke JP. Observational research, randomised trials, and two views of medical science. PLoS Med 2008;5:e67. 15. Atkins D, Eccles M, Flottorp S, et al. Systems for grading the quality of evidence and the strength of recommendations I: Critical appraisal of existing approaches The GRADE Working Group. BMC Health Serv Res 2004;4:38. 16. Rawlins M. De Testimonio: On the evidence for decisions about the use of therapeutic interventions. Clin Med 2008;8: 579–588.
The Global Ureteroscopy Study, Global GreenLightÔ Laser Study, and the Global Renal Mass Study were closed in 2012. The first five papers on URS and the first one on the Renal Mass Study have been published. The first two articles of the Global GreenLightÔ Laser study are under review. The randomized study on Narrow Band Imaging vs White Light Imaging closed in 2013.The first results are being analyzed. Ongoing project: The Irreversible Electroporation Study study for focal therapy including a pilot study, a randomized controlled trial, and a Registry. New project: The randomized study on SPIES vs White Light Imaging. New project: The Global Upper Tract-Transitional-Cell Carcinoma Study. For further information please visit: www.croesoffice.org or contact the executive director of CROES, Mrs. Sonja van Rees Vellinga ([email protected]).
112
Copyright of Journal of Endourology is the property of Mary Ann Liebert, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
