DOI: 10.1111/hir.12045
Dissertations into Practice
Abstract Pharmaceutical interventions have brought about many benefits to health, improving the population’s well-being and life expectancy. However, these interventions are not without potential harmful sideeffects and yet searching for the evidence on adverse effects is challenging. This article summarises a PhD whose main aim was to develop a better understanding of the implications of using different sources and approaches to identifying relevant data on adverse effects. The author is Su Golder, who has recently completed her PhD at the University of York and who has already published several articles on specific aspects of her research, including this journal. This article is the first in the Dissertations into Practice series to report on a PhD study, and it summarises her research in a way which emphasises the implications for practice. AM Keywords: EMBASE; information retrieval; MEDLINE; search strategies; searching
Optimising the retrieval of information on adverse drug effects Su Golder MRC Research Fellow Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK Dissertation context Pharmaceutical interventions have bought about many benefits to health, improving the population’s well-being and life expectancy. However, these interventions are not without potential harmful side-effects. Systematic reviews aim to identify, evaluate, and summarise the findings of all relevant individual studies to answer specific questions and are
generally regarded as the best evidence to inform decision-making.1 To help patients, clinicians and policy makers make balanced decisions and systematic reviews need to include both the intended benefits and unwanted adverse effects of an intervention.2 A fundamental step in any systematic review is to retrieve all the relevant studies. This requires the development of optimal search techniques. The retrieval of information on adverse effects poses particular challenges, and there are a number of factors contributing to this.3 Firstly, there is a diversity of study designs that might contain information of interest. Searching for observational studies, such as cohort studies, case–control studies, and case reports, can be problematic because of inconsistent terminology, variable indexing and a lack of research into appropriate search filters. Secondly, a wide range of data sources are available for retrieving information on adverse effects, yet little is known about their comparative value. In particular, there are many specialist databases for adverse effects, toxicity and drug information, as well as post-marketing surveillance data and tertiary sources (such as Meyler’s side-effects of drugs4 or Reactions Bulletin). Lastly, developing efficient search strategies (combinations of search terms) for use in databases (such as MEDLINE and EMBASE) which capture all the relevant literature on adverse effects is problematic. Specific difficulties arise when adverse effects terms are added to the search strategy.5 This is because adverse effects are poorly reported, inadequately indexed, inconsistently described, may not be limited to a particular condition, and specific named adverse effects may not be known at the time of searching. A better understanding of the implications of using different sources and approaches to identifying data on adverse effects is urgently required. Development of these search techniques was the primary aim of this PhD.
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
327
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Dissertations into Practice
Dissertation methods This programme of research sought to address three core research questions: • Which study designs, such as randomised control trials (RCTs) or cohort studies, provide the best evidence on adverse effects? • Which sources of information (such as MEDLINE or EMBASE) provide the most efficient yield of relevant data on adverse drug effects? • Which search strategies are most effective in retrieving relevant data on adverse drug effects from sources such as MEDLINE and EMBASE? To answer these research questions, a mixedmethod approach was adopted: • A literature review of existing methodological studies related to searching for adverse effects. • A survey of the retrieval methods used in 849 systematic reviews of adverse effects. • An evaluation of the included studies in a systematic review of adverse drug effects to assess: a the contribution of information on adverse drug effects from different sources; b the effectiveness of different search strategies for identifying information on adverse drug effects. • An evaluation of the effectiveness of different search strategies and search terms in a series of 26 systematic reviews of adverse drug effects. Literature review of existing methodological studies related to searching for adverse effects The first stage of this PhD was to identify and consolidate the existing research evidence in this area. A systematic review was undertaken, which summarised all aspects of the methodological literature to date on the retrieval of information on adverse effects. Studies were located by searching 10 databases (including MEDLINE and EMBASE) as well as reference checking, handsearching, checking conference proceedings, citation searching and discussion with experts.
Topic areas included were as follows: study design selection, such as RCTs versus cohort studies (51 included studies); the relative value of different sources of information, such as database and non-database sources (19 included studies); adverse effects database search filters (three included studies); the inclusion of unpublished material (10 included studies) and industry funded studies (six included studies); and potential bias by type of author (clinician or academic) (three included studies); year of publication (two included studies); journal impact factor (one included study); and country setting (one included study). Survey of the retrieval methods used in 849 systematic reviews of adverse effects The second stage of this programme of research aimed to summarise current practice in the retrieval of information in systematic reviews of adverse effects and to assess any apparent time trends in the methodologies employed between 1994 and 2011. The search methods used in the 849 systematic reviews of adverse effects were also compared with the methods used in other types of systematic reviews. An evaluation of the included studies in a systematic review of adverse drug effects to assess The contribution of information on adverse drug effects from different sources. Fifty-eight included papers from a systematic review of fractures associated with the diabetes drugs rosiglitazone and pioglitazone were used to assess the relative contribution of different information sources (including databases and non-database sources) in terms of identifying relevant references or studies. The effectiveness of different searching methods for identifying information on adverse drug effects. The original search strategy in this systematic review contained just two facets, the intervention: diabetes drugs (rosiglitazone and pioglitazone) and the outcome: fractures. No generic adverse effects terms (such as ‘safety’, ‘side-effect’ or ‘adverse event’) were included in the search
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
Dissertations into Practice
strategy. This meant that the effect of the addition of ‘adverse effect’ related search terms or filters could be assessed in MEDLINE and EMBASE, in terms of sensitivity and precision. An evaluation of the effectiveness of different searching methods using a series of systematic reviews of adverse drug effects Two hundred and forty-two included papers from 26 systematic reviews of adverse drug effects were used to assess the sensitivity of individual adverse effects search terms in MEDLINE, EMBASE and Science Citation Index (SCI), and the sensitivity of adverse effects search filters in MEDLINE and EMBASE. Discussion of results There are a number of important findings from this research. The literature review findings suggested that, on average, there is no difference in the results obtained from combining RCTs or combining observational studies.6 This suggests that including observational studies does not bias the results of systematic reviews of adverse effects. Furthermore, unpublished studies and data from drug manufacturers were found to provide additional data that is not covered in published studies.7,8 The highest yield of relevant studies in the systematic review of rosiglitazone and pioglitazone was obtained from searching Science Citation Index (SCI), followed by BIOSIS Previews, EMBASE and then MEDLINE.9 Similarly, previous research identified in the literature review also found that MEDLINE did not yield the highest number of relevant records.10 The results also indicated that a combination of sources is required to identify all of the data on adverse effects. It was found that adverse effects search terms are increasingly prevalent in the Title, Abstract and Indexing terms of records that contain adverse effects data. Whereas a search of both MEDLINE and EMBASE with adverse effects terms would have missed 23% of papers in 2001,5 this PhD indicates that the same search would now only miss 8% of papers.11 The most useful adverse effects search terms in both MEDLINE and
EMBASE were subheadings, such as ‘adverse effects’ in MEDLINE and ‘adverse drug reaction’ in EMBASE.12 Although a slight improvement in the reporting of search strategies in systematic reviews of adverse effects from 1994 to 2011 was identified, overall only 9% of such reviews report a reproducible search strategy. There was also some improvement in the search methodology adopted in systematic reviews of adverse effects. The number of databases searched appears to be increasing, and the proportion of reviews limiting their searches to MEDLINE or using date or language restrictions to be decreasing.13 Particular areas of concern in the methodology of systematic reviews of adverse effects are as follows: • the increase in the proportion of reviews limited to RCTs only between 1994 and 2011; • the lack of any attempt to identify unpublished data or data from pharmaceutical companies; • the potentially inappropriate selection of information sources. There were large discrepancies between the individual information sources contributing the most information on adverse effects, and those sources currently searched in systematic reviews of adverse effects. For instance, the highest number of relevant records was achieved by searching Science Citation Index (SCI) followed by BIOSIS Previews, yet only 5% and 8% of reviews of adverse effects, respectively, search this database. None of the 849 reviews of adverse effects searched Scirus, Derwent Drug File, British Library Direct, Thomson Reuters Integrity, and ADIS Clinical Trials Insight, yet these databases retrieved 29%, 28%, 26%, 22% and 21% of relevant references, respectively, in the systematic review on rosiglitazone and pioglitazone. Although MEDLINE is the most popular database and is often the only database searched, only a third of relevant references were retrieved with this database in the systematic review on rosiglitazone and pioglitazone. Implications for practice The findings from this thesis have several important implications for those conducting searches for
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
329
330
Dissertations into Practice
systematic reviews, which incorporate adverse effects. In particular, the results suggest that rather than limiting to certain study designs, it is better to try to identify a broad range of studies. This is particularly relevant in reviews in which there are few RCTs identified, or where the reporting of adverse effects in RCTs is poor. When few RCTs are identified that report harms, this can lead to a misconception that a given intervention is safe, when its safety is actually unknown. Evidence from this programme of research indicates that searches should be undertaken to retrieve unpublished studies and industry funded data. However, identifying industry funded studies and the unpublished literature is challenging.14 Searches might need to be extended beyond standard bibliographic databases to identify data from specialist websites, company and other study/trial registries, regulatory agencies [such as Health Canada and the US Food and Drug Administration (FDA)], conference abstracts, contacting experts and reference lists. Contacting industry for information is also notoriously slow and time consuming with a low response rate. The particular information sources that should be searched in any systematic review will vary depending on the topic area of the review, and it is difficult to generalise the findings from this research to all reviews. However, it is clear from this research that searchers should not rely solely on MEDLINE for information on adverse effects but attempt to identify data on adverse effects from multiple sources, and use additional techniques such as handsearching and reference checking. Previous research indicated that adverse effect search terms are not to be relied upon and that any search strategy, including adverse effects search terms, can miss a high volume of relevant references. Although caution still needs to be exercised, search strategies in MEDLINE and EMBASE can now include adverse effects terms or adverse effects search filters with reasonable sensitivity. If improvements continue, searchers will be able to use adverse effects search terms and search filters with more confidence. Authors of systematic reviews need to improve the reporting of search strategies for adverse effects and report more reproducible search strategies in order for readers to be convinced by the
methodology and for update searches to be undertaken. Ways in which authors could improve reporting include the following: involving an information professional, adhering to guidelines and using Web appendices and supplementary material options for journal articles. Conclusion Although there have been improvements in the search methods used in systematic reviews of adverse effects, there are still some major discrepancies between the methods advocated in the literature and current practice. These are particularly apparent in the selection of databases searched, the lack of searches for unpublished data and industry funded studies, and the increasing restriction of included studies to RCTs only. In addition, poor reporting of search strategies in systematic reviews of adverse effects remains a major obstacle to readers. The results of this PhD suggest that searches should be undertaken for industry funded data, unpublished data and all study types. In relation to where and how to search, it is apparent that a combination of sources is required to identify adverse drug effects data and that MEDLINE is unlikely to contribute the highest yield of relevant papers. Evidence also suggests that using adverse effects search filters for databases such as MEDLINE and EMBASE can be useful, and the success of adverse effects search terms and filters to capture relevant papers has improved. Lastly and most importantly, to redress the continuing overemphasis on benefits, the development and improvement of methods to quantify adverse effects should be made a key research priority. References 1 Centre for Reviews and Dissemination Systematic Reviews: CRD’s Guidance for Undertaking Reviews in Healthcare, 3rd edn. York: University of York, Centre for Reviews and Dissemination, 2009. 2 Keech, A. C., Wonders, S. M., Cook, D. I. & Gebski, V. J. Balancing the outcomes: Reporting adverse events. Medical Journal of Australia 2004, 181, 215–218.
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
Dissertations into Practice 3 Loke, Y. K., Price, D. & Herxheimer, A. Chapter 14: Adverse effects. In: Higgins, J. P. T. & Green, S.. (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (Updated March 2011): The Cochrane Collaboration, 2011. [WWW document]. www.cochrane-handbook. org. 4 Dukes, M. N. G. & Aronson, J. K. Meyler’s Side Effects of Drugs: An Encyclopedia of Adverse Reactions and Interactions, 15th edn. Oxford: Elsevier, 2006. 5 Derry, S., Loke, Y. K. & Aronson, J. K. Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials. BMC Medical Research Methodology 2001, 1, 7. 6 Golder, S., Loke, Y. K. & Bland, M.. Meta-analyses of adverse effects data derived from randomised controlled trials as compared to observational studies: methodological overview. PLOS Medicine 2011, 8 , e1001026. 7 Golder, S., Loke, Y. K. & Bland, M. Unpublished data can be of value in systematic reviews of adverse effects: methodological overview. Journal of Clinical Epidemiology 2010, 63, 1071–1081. 8 Golder, S. & Loke, Y. K. Is there evidence for biased reporting of published adverse effects data in pharmaceutical industry-funded studies? British Journal of Clinical Pharmacology 2008, 66, 767–773. 9 Golder, S. & Loke, Y. K. The contribution of different information sources for adverse effects data. International Journal of Technology Assessment in Health Care 2012, 28, 133–137. 10 Golder, S. & Loke, Y. K. Sources of information on adverse effects: a systematic review. Health Information & Libraries Journal 2010, 27, 176–190.
11 Golder, S. & Loke, Y. K. Failure or success of electronic search strategies to identify adverse effects data. Journal of the Medical Library Association 2012, 100, 130–134. 12 Golder, S. & Loke, Y. K. The performance of adverse effects search filters in MEDLINE and EMBASE. Health Information & Libraries Journal 2012, 29 , 141–151. 13 Golder, S., Loke, Y. K. & Zorzela, L. Some improvements are apparent in identifying adverse effects in systematic reviews from 1994 to 2011. Journal of Clinical Epidemiology 2013, 66, 253–260. 14 Chou, R., Aronson, N., Atkins, D., Ismaila, A. S., Santaguida, P., Smith, D. H., Whitlock, E., Wilt, T. J. & Moher, D. AHRQ Series Paper 4: assessing harms when comparing medical interventions: AHRQ and the Effective Health-Care Program. Journal of Clinical Epidemiology 2010, 63 , 502– 512. Received 19 August 2013; Accepted 30 August 2013
For details on how to contribute to this feature please contact: Audrey Marshall Watts Building, Lewes Road Brighton BN2 4GJ, UK Tel: 01273 642420 E-mail: [email protected]
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
331
Dissertations into Practice
Abstract Pharmaceutical interventions have brought about many benefits to health, improving the population’s well-being and life expectancy. However, these interventions are not without potential harmful sideeffects and yet searching for the evidence on adverse effects is challenging. This article summarises a PhD whose main aim was to develop a better understanding of the implications of using different sources and approaches to identifying relevant data on adverse effects. The author is Su Golder, who has recently completed her PhD at the University of York and who has already published several articles on specific aspects of her research, including this journal. This article is the first in the Dissertations into Practice series to report on a PhD study, and it summarises her research in a way which emphasises the implications for practice. AM Keywords: EMBASE; information retrieval; MEDLINE; search strategies; searching
Optimising the retrieval of information on adverse drug effects Su Golder MRC Research Fellow Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK Dissertation context Pharmaceutical interventions have bought about many benefits to health, improving the population’s well-being and life expectancy. However, these interventions are not without potential harmful side-effects. Systematic reviews aim to identify, evaluate, and summarise the findings of all relevant individual studies to answer specific questions and are
generally regarded as the best evidence to inform decision-making.1 To help patients, clinicians and policy makers make balanced decisions and systematic reviews need to include both the intended benefits and unwanted adverse effects of an intervention.2 A fundamental step in any systematic review is to retrieve all the relevant studies. This requires the development of optimal search techniques. The retrieval of information on adverse effects poses particular challenges, and there are a number of factors contributing to this.3 Firstly, there is a diversity of study designs that might contain information of interest. Searching for observational studies, such as cohort studies, case–control studies, and case reports, can be problematic because of inconsistent terminology, variable indexing and a lack of research into appropriate search filters. Secondly, a wide range of data sources are available for retrieving information on adverse effects, yet little is known about their comparative value. In particular, there are many specialist databases for adverse effects, toxicity and drug information, as well as post-marketing surveillance data and tertiary sources (such as Meyler’s side-effects of drugs4 or Reactions Bulletin). Lastly, developing efficient search strategies (combinations of search terms) for use in databases (such as MEDLINE and EMBASE) which capture all the relevant literature on adverse effects is problematic. Specific difficulties arise when adverse effects terms are added to the search strategy.5 This is because adverse effects are poorly reported, inadequately indexed, inconsistently described, may not be limited to a particular condition, and specific named adverse effects may not be known at the time of searching. A better understanding of the implications of using different sources and approaches to identifying data on adverse effects is urgently required. Development of these search techniques was the primary aim of this PhD.
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
327
328
Dissertations into Practice
Dissertation methods This programme of research sought to address three core research questions: • Which study designs, such as randomised control trials (RCTs) or cohort studies, provide the best evidence on adverse effects? • Which sources of information (such as MEDLINE or EMBASE) provide the most efficient yield of relevant data on adverse drug effects? • Which search strategies are most effective in retrieving relevant data on adverse drug effects from sources such as MEDLINE and EMBASE? To answer these research questions, a mixedmethod approach was adopted: • A literature review of existing methodological studies related to searching for adverse effects. • A survey of the retrieval methods used in 849 systematic reviews of adverse effects. • An evaluation of the included studies in a systematic review of adverse drug effects to assess: a the contribution of information on adverse drug effects from different sources; b the effectiveness of different search strategies for identifying information on adverse drug effects. • An evaluation of the effectiveness of different search strategies and search terms in a series of 26 systematic reviews of adverse drug effects. Literature review of existing methodological studies related to searching for adverse effects The first stage of this PhD was to identify and consolidate the existing research evidence in this area. A systematic review was undertaken, which summarised all aspects of the methodological literature to date on the retrieval of information on adverse effects. Studies were located by searching 10 databases (including MEDLINE and EMBASE) as well as reference checking, handsearching, checking conference proceedings, citation searching and discussion with experts.
Topic areas included were as follows: study design selection, such as RCTs versus cohort studies (51 included studies); the relative value of different sources of information, such as database and non-database sources (19 included studies); adverse effects database search filters (three included studies); the inclusion of unpublished material (10 included studies) and industry funded studies (six included studies); and potential bias by type of author (clinician or academic) (three included studies); year of publication (two included studies); journal impact factor (one included study); and country setting (one included study). Survey of the retrieval methods used in 849 systematic reviews of adverse effects The second stage of this programme of research aimed to summarise current practice in the retrieval of information in systematic reviews of adverse effects and to assess any apparent time trends in the methodologies employed between 1994 and 2011. The search methods used in the 849 systematic reviews of adverse effects were also compared with the methods used in other types of systematic reviews. An evaluation of the included studies in a systematic review of adverse drug effects to assess The contribution of information on adverse drug effects from different sources. Fifty-eight included papers from a systematic review of fractures associated with the diabetes drugs rosiglitazone and pioglitazone were used to assess the relative contribution of different information sources (including databases and non-database sources) in terms of identifying relevant references or studies. The effectiveness of different searching methods for identifying information on adverse drug effects. The original search strategy in this systematic review contained just two facets, the intervention: diabetes drugs (rosiglitazone and pioglitazone) and the outcome: fractures. No generic adverse effects terms (such as ‘safety’, ‘side-effect’ or ‘adverse event’) were included in the search
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
Dissertations into Practice
strategy. This meant that the effect of the addition of ‘adverse effect’ related search terms or filters could be assessed in MEDLINE and EMBASE, in terms of sensitivity and precision. An evaluation of the effectiveness of different searching methods using a series of systematic reviews of adverse drug effects Two hundred and forty-two included papers from 26 systematic reviews of adverse drug effects were used to assess the sensitivity of individual adverse effects search terms in MEDLINE, EMBASE and Science Citation Index (SCI), and the sensitivity of adverse effects search filters in MEDLINE and EMBASE. Discussion of results There are a number of important findings from this research. The literature review findings suggested that, on average, there is no difference in the results obtained from combining RCTs or combining observational studies.6 This suggests that including observational studies does not bias the results of systematic reviews of adverse effects. Furthermore, unpublished studies and data from drug manufacturers were found to provide additional data that is not covered in published studies.7,8 The highest yield of relevant studies in the systematic review of rosiglitazone and pioglitazone was obtained from searching Science Citation Index (SCI), followed by BIOSIS Previews, EMBASE and then MEDLINE.9 Similarly, previous research identified in the literature review also found that MEDLINE did not yield the highest number of relevant records.10 The results also indicated that a combination of sources is required to identify all of the data on adverse effects. It was found that adverse effects search terms are increasingly prevalent in the Title, Abstract and Indexing terms of records that contain adverse effects data. Whereas a search of both MEDLINE and EMBASE with adverse effects terms would have missed 23% of papers in 2001,5 this PhD indicates that the same search would now only miss 8% of papers.11 The most useful adverse effects search terms in both MEDLINE and
EMBASE were subheadings, such as ‘adverse effects’ in MEDLINE and ‘adverse drug reaction’ in EMBASE.12 Although a slight improvement in the reporting of search strategies in systematic reviews of adverse effects from 1994 to 2011 was identified, overall only 9% of such reviews report a reproducible search strategy. There was also some improvement in the search methodology adopted in systematic reviews of adverse effects. The number of databases searched appears to be increasing, and the proportion of reviews limiting their searches to MEDLINE or using date or language restrictions to be decreasing.13 Particular areas of concern in the methodology of systematic reviews of adverse effects are as follows: • the increase in the proportion of reviews limited to RCTs only between 1994 and 2011; • the lack of any attempt to identify unpublished data or data from pharmaceutical companies; • the potentially inappropriate selection of information sources. There were large discrepancies between the individual information sources contributing the most information on adverse effects, and those sources currently searched in systematic reviews of adverse effects. For instance, the highest number of relevant records was achieved by searching Science Citation Index (SCI) followed by BIOSIS Previews, yet only 5% and 8% of reviews of adverse effects, respectively, search this database. None of the 849 reviews of adverse effects searched Scirus, Derwent Drug File, British Library Direct, Thomson Reuters Integrity, and ADIS Clinical Trials Insight, yet these databases retrieved 29%, 28%, 26%, 22% and 21% of relevant references, respectively, in the systematic review on rosiglitazone and pioglitazone. Although MEDLINE is the most popular database and is often the only database searched, only a third of relevant references were retrieved with this database in the systematic review on rosiglitazone and pioglitazone. Implications for practice The findings from this thesis have several important implications for those conducting searches for
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
329
330
Dissertations into Practice
systematic reviews, which incorporate adverse effects. In particular, the results suggest that rather than limiting to certain study designs, it is better to try to identify a broad range of studies. This is particularly relevant in reviews in which there are few RCTs identified, or where the reporting of adverse effects in RCTs is poor. When few RCTs are identified that report harms, this can lead to a misconception that a given intervention is safe, when its safety is actually unknown. Evidence from this programme of research indicates that searches should be undertaken to retrieve unpublished studies and industry funded data. However, identifying industry funded studies and the unpublished literature is challenging.14 Searches might need to be extended beyond standard bibliographic databases to identify data from specialist websites, company and other study/trial registries, regulatory agencies [such as Health Canada and the US Food and Drug Administration (FDA)], conference abstracts, contacting experts and reference lists. Contacting industry for information is also notoriously slow and time consuming with a low response rate. The particular information sources that should be searched in any systematic review will vary depending on the topic area of the review, and it is difficult to generalise the findings from this research to all reviews. However, it is clear from this research that searchers should not rely solely on MEDLINE for information on adverse effects but attempt to identify data on adverse effects from multiple sources, and use additional techniques such as handsearching and reference checking. Previous research indicated that adverse effect search terms are not to be relied upon and that any search strategy, including adverse effects search terms, can miss a high volume of relevant references. Although caution still needs to be exercised, search strategies in MEDLINE and EMBASE can now include adverse effects terms or adverse effects search filters with reasonable sensitivity. If improvements continue, searchers will be able to use adverse effects search terms and search filters with more confidence. Authors of systematic reviews need to improve the reporting of search strategies for adverse effects and report more reproducible search strategies in order for readers to be convinced by the
methodology and for update searches to be undertaken. Ways in which authors could improve reporting include the following: involving an information professional, adhering to guidelines and using Web appendices and supplementary material options for journal articles. Conclusion Although there have been improvements in the search methods used in systematic reviews of adverse effects, there are still some major discrepancies between the methods advocated in the literature and current practice. These are particularly apparent in the selection of databases searched, the lack of searches for unpublished data and industry funded studies, and the increasing restriction of included studies to RCTs only. In addition, poor reporting of search strategies in systematic reviews of adverse effects remains a major obstacle to readers. The results of this PhD suggest that searches should be undertaken for industry funded data, unpublished data and all study types. In relation to where and how to search, it is apparent that a combination of sources is required to identify adverse drug effects data and that MEDLINE is unlikely to contribute the highest yield of relevant papers. Evidence also suggests that using adverse effects search filters for databases such as MEDLINE and EMBASE can be useful, and the success of adverse effects search terms and filters to capture relevant papers has improved. Lastly and most importantly, to redress the continuing overemphasis on benefits, the development and improvement of methods to quantify adverse effects should be made a key research priority. References 1 Centre for Reviews and Dissemination Systematic Reviews: CRD’s Guidance for Undertaking Reviews in Healthcare, 3rd edn. York: University of York, Centre for Reviews and Dissemination, 2009. 2 Keech, A. C., Wonders, S. M., Cook, D. I. & Gebski, V. J. Balancing the outcomes: Reporting adverse events. Medical Journal of Australia 2004, 181, 215–218.
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
Dissertations into Practice 3 Loke, Y. K., Price, D. & Herxheimer, A. Chapter 14: Adverse effects. In: Higgins, J. P. T. & Green, S.. (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (Updated March 2011): The Cochrane Collaboration, 2011. [WWW document]. www.cochrane-handbook. org. 4 Dukes, M. N. G. & Aronson, J. K. Meyler’s Side Effects of Drugs: An Encyclopedia of Adverse Reactions and Interactions, 15th edn. Oxford: Elsevier, 2006. 5 Derry, S., Loke, Y. K. & Aronson, J. K. Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials. BMC Medical Research Methodology 2001, 1, 7. 6 Golder, S., Loke, Y. K. & Bland, M.. Meta-analyses of adverse effects data derived from randomised controlled trials as compared to observational studies: methodological overview. PLOS Medicine 2011, 8 , e1001026. 7 Golder, S., Loke, Y. K. & Bland, M. Unpublished data can be of value in systematic reviews of adverse effects: methodological overview. Journal of Clinical Epidemiology 2010, 63, 1071–1081. 8 Golder, S. & Loke, Y. K. Is there evidence for biased reporting of published adverse effects data in pharmaceutical industry-funded studies? British Journal of Clinical Pharmacology 2008, 66, 767–773. 9 Golder, S. & Loke, Y. K. The contribution of different information sources for adverse effects data. International Journal of Technology Assessment in Health Care 2012, 28, 133–137. 10 Golder, S. & Loke, Y. K. Sources of information on adverse effects: a systematic review. Health Information & Libraries Journal 2010, 27, 176–190.
11 Golder, S. & Loke, Y. K. Failure or success of electronic search strategies to identify adverse effects data. Journal of the Medical Library Association 2012, 100, 130–134. 12 Golder, S. & Loke, Y. K. The performance of adverse effects search filters in MEDLINE and EMBASE. Health Information & Libraries Journal 2012, 29 , 141–151. 13 Golder, S., Loke, Y. K. & Zorzela, L. Some improvements are apparent in identifying adverse effects in systematic reviews from 1994 to 2011. Journal of Clinical Epidemiology 2013, 66, 253–260. 14 Chou, R., Aronson, N., Atkins, D., Ismaila, A. S., Santaguida, P., Smith, D. H., Whitlock, E., Wilt, T. J. & Moher, D. AHRQ Series Paper 4: assessing harms when comparing medical interventions: AHRQ and the Effective Health-Care Program. Journal of Clinical Epidemiology 2010, 63 , 502– 512. Received 19 August 2013; Accepted 30 August 2013
For details on how to contribute to this feature please contact: Audrey Marshall Watts Building, Lewes Road Brighton BN2 4GJ, UK Tel: 01273 642420 E-mail: [email protected]
© 2013 The authors. Health Information and Libraries Journal © 2013 Health Libraries Group Health Information & Libraries Journal, 30, pp. 327–331
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