Eur J Clin Pharmacol (2014) 70:313–318 DOI 10.1007/s00228-013-1612-7
PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
Checklist for standardized reporting of drug–drug interaction management guidelines Annemieke Floor-Schreudering & Arjen F. J. Geerts & Jeffrey K. Aronson & Marcel L. Bouvy & Robin E. Ferner & Peter A. G. M. De Smet
Received: 15 July 2013 / Accepted: 6 November 2013 / Published online: 5 December 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Purpose Inconsistencies and omissions in drug–drug interaction (DDI) management guidelines may lead to harm and suboptimal therapy. The purpose of this study was to define a checklist for DDI management guidelines to help developers produce high-quality guidelines that will support healthcare providers in clinical practice. Methods We carried out a two-round Delphi process with an international panel of healthcare providers, most of whom are pharmacists involved in providing DDI information, in order to select those items that should be addressed in DDI
Electronic supplementary material The online version of this article (doi:10.1007/s00228-013-1612-7) contains supplementary material, which is available to authorized users. A. Floor-Schreudering (*) : M. L. Bouvy SIR Institute for Pharmacy Practice and Policy, Theda Mansholtstraat 5B, 2331 JE Leiden, The Netherlands e-mail: [email protected] A. Floor-Schreudering : P. A. G. M. De Smet Departments of Clinical Pharmacy and IQ Healthcare, University Medical Centre St Radboud, Nijmegen, The Netherlands A. F. J. Geerts : M. L. Bouvy Division Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands J. K. Aronson Department of Primary Care Health Sciences, University of Oxford, Oxford, UK R. E. Ferner West Midlands Centre for Adverse Drug Reactions City Hospital, Birmingham, UK P. A. G. M. De Smet Scientific Institute of Dutch Pharmacists (WINAp), The Hague, The Netherlands
management guidelines (including grading systems that could be used). Results Twenty-three panellists reached consensus on 19 items in two main domains. These were consolidated into a checklist of 15 elements for standardized reporting in management guidelines. For each element a description is provided to specify what information should be documented in that specific element. Conclusions It was possible to reach a broad consensus on which relevant items should be included in a checklist for the development of DDI management guidelines. Keywords Practice guidelines . Evidence-based medicine . drug–drug interactions . Checklist . Assessment . Management
Introduction The main purpose of clinical guidelines is to improve patient care, and these should therefore meet criteria that ensure good quality [1]. Several instruments have been developed to assess the quality of clinical practice guidelines, including checklists to specify the nature of information in guidelines [2], appraisal instruments to evaluate the quality of guidelines [3, 4] and systems for consistent rating of the quality of evidence and the strength of the recommendations [5]. Such instruments have occasionally been used to develop or evaluate guidelines for the management of drug–drug interactions (DDIs) [6–10]. However, a well-defined standard for guidelines on the practical management of (potential) drug–drug interactions is not yet available. There is no consensus in the literature about how evidence relating to the harm that DDIs may cause should be graded, and information on susceptibility factors is not yet systematically reviewed in DDI management guidelines [6, 10, 11]. Recommendations
314
on how to manage DDIs are not always sufficiently detailed (e.g. “monitor electrolytes” rather than the more precise “monitor potassium and sodium every 4–6 weeks”) [12] or supported by analyses of cost-effectiveness [10]. These inadequacies contribute to inconsistencies between information sources with respect to the inclusion of DDIs, the grading of their potential seriousness and the grading of the quality of the underlying evidence [13–17]. Consequently, management of DDIs will be inconsistent and may be guided by unclear or unsatisfactory advice, so that patients may sometimes be harmed by an avoidable DDI and may sometimes be denied therapeutic benefit by an overcautious approach [18]. The aim of our study was to define a checklist for developers of DDI management guidelines. Such a checklist should assist developers in producing high-quality drug–drug interaction management guidelines and support healthcare providers in the practical application of the guidelines.
Methods We carried out a two-round Delphi process with a large international panel of healthcare providers, most of whom are pharmacists involved in providing DDI information, in order to select the items that should be addressed in DDI management guidelines, including grading systems that could be used [9, 19, 20]. We identified and contacted potential panel members through contact information available in the literature and through our research network based on predetermined inclusion criteria: the potential panel members had published scientific papers in the field of DDIs and/or were involved in writing DDI information sources and had either a medical or a pharmaceutical background (general practitioners, medical specialists, clinical pharmacologists, community pharmacists, hospital pharmacists). Our aim was to approach a broad range of representatives from a variety of countries. From the 44 invited panellists who fulfilled these criteria, 32 agreed to participate. The main reason for non-participation was lack of time. The panellists were asked to express their views on the relevance and comprehensiveness of a set of potential items for DDI management guidelines and their preferences on proposed grading systems. We assembled an initial set of two main domains with 19 potential guideline items from validated general instruments to assess and improve the quality of clinical practice guidelines [2–5, 21–23], the systems for grading the levels of evidence and the strengths of recommendations [24] and the published instruments for developing or evaluating guidelines for the management of DDIs [see Electronic Supplementary Material (ESM) Appendix A]).
Eur J Clin Pharmacol (2014) 70:313–318
The panellists received a set of potential guideline items that included a detailed description of each item. They also received instructions on how to indicate their level of (dis)agreement on the relevance of each item in the management of DDIs (a nine-point scale, in which point 5 was neutral, according to the RAND appropriateness method [25]). Rating an item as 9 indicated strong agreement that it was relevant; rating an item as 1 indicated strong disagreement [25]. We used the pretested online survey tool NetQ (http://netq. co.uk/lang/EN/) to present the questionnaires to the panellists. Online rating permits accurate and efficient data capture and analysis [26]. In the first Delphi round the panellists were asked to score each item and to provide comments regarding their scores. They were also allowed to add, modify or reword items. The decision to include items in round 2 was based on an analysis of the scores for each of the items, the criteria for consensus on acceptance and rejection of items (see Analysis), the panellists’ comments or suggestions and the literature underpinning the initial set of items. All newly suggested items were discussed and classified as (1) suitable for inclusion in the proposed list of items, (2) of uncertain suitability for inclusion and (3) unsuitable for inclusion because, for example, an item was already covered by guideline items in the initial set. Suggestions classified as 1 and 2 were presented as new items to the panellists in the second round. All panellists received feedback on the decisions from the first Delphi round, including the level of agreement for each item, the panellist’s individual score, the level of consensus and a summary of the free text comments of the panellists. In the second Delphi round all those who participated in round 1 were sent the second questionnaire and asked to rate the items. Again, they were asked to provide reasons for their scores. The research team then decided which items were to be accepted, using the same criteria as in the first round. For some items minor textual changes were made for clarification. The results of the second round were presented to the panellists in a final report for information purposes only. Finally, closely related accepted items were consolidated into a checklist of elements for standardized reporting. Analysis In both rounds, the level of agreement with each item and the level of consensus among the panellists were calculated using the RAND method, which is based on the median value and the dispersion of the rating results. A median of 7–9 indicates that “the item is relevant”, a median of 4–6 indicates “uncertain whether the item is relevant” and a median of 1–3 indicates that “the item is not relevant”. For evaluation of the variation among the ratings, we used the Disagreement Index (DI). If the DI was
PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
Checklist for standardized reporting of drug–drug interaction management guidelines Annemieke Floor-Schreudering & Arjen F. J. Geerts & Jeffrey K. Aronson & Marcel L. Bouvy & Robin E. Ferner & Peter A. G. M. De Smet
Received: 15 July 2013 / Accepted: 6 November 2013 / Published online: 5 December 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Purpose Inconsistencies and omissions in drug–drug interaction (DDI) management guidelines may lead to harm and suboptimal therapy. The purpose of this study was to define a checklist for DDI management guidelines to help developers produce high-quality guidelines that will support healthcare providers in clinical practice. Methods We carried out a two-round Delphi process with an international panel of healthcare providers, most of whom are pharmacists involved in providing DDI information, in order to select those items that should be addressed in DDI
Electronic supplementary material The online version of this article (doi:10.1007/s00228-013-1612-7) contains supplementary material, which is available to authorized users. A. Floor-Schreudering (*) : M. L. Bouvy SIR Institute for Pharmacy Practice and Policy, Theda Mansholtstraat 5B, 2331 JE Leiden, The Netherlands e-mail: [email protected] A. Floor-Schreudering : P. A. G. M. De Smet Departments of Clinical Pharmacy and IQ Healthcare, University Medical Centre St Radboud, Nijmegen, The Netherlands A. F. J. Geerts : M. L. Bouvy Division Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands J. K. Aronson Department of Primary Care Health Sciences, University of Oxford, Oxford, UK R. E. Ferner West Midlands Centre for Adverse Drug Reactions City Hospital, Birmingham, UK P. A. G. M. De Smet Scientific Institute of Dutch Pharmacists (WINAp), The Hague, The Netherlands
management guidelines (including grading systems that could be used). Results Twenty-three panellists reached consensus on 19 items in two main domains. These were consolidated into a checklist of 15 elements for standardized reporting in management guidelines. For each element a description is provided to specify what information should be documented in that specific element. Conclusions It was possible to reach a broad consensus on which relevant items should be included in a checklist for the development of DDI management guidelines. Keywords Practice guidelines . Evidence-based medicine . drug–drug interactions . Checklist . Assessment . Management
Introduction The main purpose of clinical guidelines is to improve patient care, and these should therefore meet criteria that ensure good quality [1]. Several instruments have been developed to assess the quality of clinical practice guidelines, including checklists to specify the nature of information in guidelines [2], appraisal instruments to evaluate the quality of guidelines [3, 4] and systems for consistent rating of the quality of evidence and the strength of the recommendations [5]. Such instruments have occasionally been used to develop or evaluate guidelines for the management of drug–drug interactions (DDIs) [6–10]. However, a well-defined standard for guidelines on the practical management of (potential) drug–drug interactions is not yet available. There is no consensus in the literature about how evidence relating to the harm that DDIs may cause should be graded, and information on susceptibility factors is not yet systematically reviewed in DDI management guidelines [6, 10, 11]. Recommendations
314
on how to manage DDIs are not always sufficiently detailed (e.g. “monitor electrolytes” rather than the more precise “monitor potassium and sodium every 4–6 weeks”) [12] or supported by analyses of cost-effectiveness [10]. These inadequacies contribute to inconsistencies between information sources with respect to the inclusion of DDIs, the grading of their potential seriousness and the grading of the quality of the underlying evidence [13–17]. Consequently, management of DDIs will be inconsistent and may be guided by unclear or unsatisfactory advice, so that patients may sometimes be harmed by an avoidable DDI and may sometimes be denied therapeutic benefit by an overcautious approach [18]. The aim of our study was to define a checklist for developers of DDI management guidelines. Such a checklist should assist developers in producing high-quality drug–drug interaction management guidelines and support healthcare providers in the practical application of the guidelines.
Methods We carried out a two-round Delphi process with a large international panel of healthcare providers, most of whom are pharmacists involved in providing DDI information, in order to select the items that should be addressed in DDI management guidelines, including grading systems that could be used [9, 19, 20]. We identified and contacted potential panel members through contact information available in the literature and through our research network based on predetermined inclusion criteria: the potential panel members had published scientific papers in the field of DDIs and/or were involved in writing DDI information sources and had either a medical or a pharmaceutical background (general practitioners, medical specialists, clinical pharmacologists, community pharmacists, hospital pharmacists). Our aim was to approach a broad range of representatives from a variety of countries. From the 44 invited panellists who fulfilled these criteria, 32 agreed to participate. The main reason for non-participation was lack of time. The panellists were asked to express their views on the relevance and comprehensiveness of a set of potential items for DDI management guidelines and their preferences on proposed grading systems. We assembled an initial set of two main domains with 19 potential guideline items from validated general instruments to assess and improve the quality of clinical practice guidelines [2–5, 21–23], the systems for grading the levels of evidence and the strengths of recommendations [24] and the published instruments for developing or evaluating guidelines for the management of DDIs [see Electronic Supplementary Material (ESM) Appendix A]).
Eur J Clin Pharmacol (2014) 70:313–318
The panellists received a set of potential guideline items that included a detailed description of each item. They also received instructions on how to indicate their level of (dis)agreement on the relevance of each item in the management of DDIs (a nine-point scale, in which point 5 was neutral, according to the RAND appropriateness method [25]). Rating an item as 9 indicated strong agreement that it was relevant; rating an item as 1 indicated strong disagreement [25]. We used the pretested online survey tool NetQ (http://netq. co.uk/lang/EN/) to present the questionnaires to the panellists. Online rating permits accurate and efficient data capture and analysis [26]. In the first Delphi round the panellists were asked to score each item and to provide comments regarding their scores. They were also allowed to add, modify or reword items. The decision to include items in round 2 was based on an analysis of the scores for each of the items, the criteria for consensus on acceptance and rejection of items (see Analysis), the panellists’ comments or suggestions and the literature underpinning the initial set of items. All newly suggested items were discussed and classified as (1) suitable for inclusion in the proposed list of items, (2) of uncertain suitability for inclusion and (3) unsuitable for inclusion because, for example, an item was already covered by guideline items in the initial set. Suggestions classified as 1 and 2 were presented as new items to the panellists in the second round. All panellists received feedback on the decisions from the first Delphi round, including the level of agreement for each item, the panellist’s individual score, the level of consensus and a summary of the free text comments of the panellists. In the second Delphi round all those who participated in round 1 were sent the second questionnaire and asked to rate the items. Again, they were asked to provide reasons for their scores. The research team then decided which items were to be accepted, using the same criteria as in the first round. For some items minor textual changes were made for clarification. The results of the second round were presented to the panellists in a final report for information purposes only. Finally, closely related accepted items were consolidated into a checklist of elements for standardized reporting. Analysis In both rounds, the level of agreement with each item and the level of consensus among the panellists were calculated using the RAND method, which is based on the median value and the dispersion of the rating results. A median of 7–9 indicates that “the item is relevant”, a median of 4–6 indicates “uncertain whether the item is relevant” and a median of 1–3 indicates that “the item is not relevant”. For evaluation of the variation among the ratings, we used the Disagreement Index (DI). If the DI was
