A wide variety of difficulties occur in finding and using information in clinical guidelines, some of which contribute to patient harm. Difficulty finding the correct guideline was the most common type of guideline-related incident, and several deaths were reported in incident reports following guideline-related medication errors. Difficulties finding and using information were most frequently associated with guidelines produced by specific local organisations (particularly acute hospitals) in relation to either the prescribing or administration of typical ‘high risk’ parenteral drugs, particularly inappropriately omitted medicines and incorrect drug doses or frequencies. Approximately 3200 guideline-related incidents are a small proportion of the more than 1.2 million medication errors reported to the NRLS during the study period, let alone the 237 million medication errors estimated to occur in England each year [1]. However, this figure is likely to be a significant underestimate, as 40% of reports contained insufficient information to determine whether they were linked to difficulties finding and using information in clinical guidelines. In addition, it is likely that the initial search of the NRLS database did not recover all reports of guideline-related incidents, especially as awareness of the contribution to medication errors of difficulties finding and using information is likely to be low among incident reporters.

The present study makes an important contribution to the literature by providing the first detailed examination of how difficulties in the use of guidelines contribute to medication errors in clinical practice. Previous studies of medication errors have identified that difficulties using guidelines can contribute to both prescribing [3,4,5,6,7,8,9] and administration errors [10,11,12,13]. However, these have not considered the guidelines use process in sufficient detail to identify that problems with both finding and using information can contribute to medication errors. The exception is a study of simulated rather than actual practice, which identified 21 guidelines-use discrepancies contributing to a medication error, of which 14 discrepancies related to finding the guideline and seven discrepancies related to reading it [14]. Similarly, previous user testing studies have identified problems finding and understanding information in guidelines, but were not designed to investigate a subsequent contribution to medication errors [19, 20, 27, 28].

The present study is also the first to quantify the reported level of harm associated with guideline-related medication incidents in practice, although a previous in situ simulation study that compared the use of ‘standard’ and ‘modified following iterative user testing’ intravenous administration guidelines rated the potential clinical significance of 280 guideline-related errors [22]. Six were likely to result in severe consequences, 214 in moderate consequences and 60 in minor consequences. As this previous study considered only the high-risk route of intravenous drug administration, it is unsurprising that the present study (which includes all routes of drug administration) observed a lower proportion of harmful incidents.

The contribution of guidelines produced by local organisations to medication errors has not been investigated by previous studies, although this has been highlighted in relation to national guidelines such as the British National Formulary (particularly dose and frequency errors) [4, 29] and the NHS Injectable Medicines Guide [14, 22]. The present study is also the first to investigate all types of guideline-related medication incident and has thus demonstrated an approximately equal contribution to both prescribing and administration errors, whereas previous studies were not able to draw comparisons between types of medication error.

The results suggest that actions to reduce the contribution of difficulties finding and using information in clinical guidelines to medication errors may reduce medication-related harm. This especially applies to local guidelines relating to both the prescribing and administration of high-risk drugs in acute settings. Such work should focus on how easily accessible guidelines are, as well as the guidelines themselves. Both simplicity of the message given within guidelines and the formatting of guidelines may be important to address [17], and iterative user testing and subsequent modification of guidelines may be an effective technique to address these concerns [19, 20, 22, 27]. While local hospital guidelines were the most commonly identified as contributing to errors, and focusing on these is therefore important, the same principles should also be applied to all guidelines. In addition, those reporting, monitoring and investigating medication-related incidents should be aware of guidelines as a potential contributing factor and ensure details are reported and appropriate actions taken.

The process of iterative user testing and modification of intravenous drug administration guidelines has been shown to reduce the frequency of medication administration errors and is a cost-effective approach [22, 23], but this has not been investigated for the prescribing errors linked to local guidelines that were prevalent in the findings of the present study. This question should therefore be addressed by future research, as user testing and subsequent modification has the potential to improve local prescribing guideline design and thus prevent medication errors. Such research should also focus on the development of user testing processes that are feasible given the resources available within individual healthcare providers. While iterative user testing and subsequent modification has been shown to make it easier for health professionals to find and understand information within one specific guideline [19, 20, 27], it does not address the process of finding the correct guideline to use, which contributed to many of incidents reported in the present study. Future research should therefore investigate whether techniques such as iterative usability testing of wider guideline information systems [28] are able to prevent further medication errors. Given the limitations of research based on voluntary reporting of medication incidents, future studies utilising prospective qualitative or quantitative data collection from staff involved in incidents would give greater certainty about the characteristics and prevalence of guideline-related medication errors. This is especially important in sectors such as primary care, which are underrepresented in the voluntary incident report data used in the present study. In addition, all future research into the causes of medication errors should consider the potential contribution of difficulties finding and using information in guidelines.

A retrospective analysis of a national database has the advantage of giving a broad pool of evidence across different locations and settings within England and Wales. However, incident reports have a number of limitations. The most significant of these is underreporting, with as few as 0.12% of patient safety incidents reported [30,31,32], leading to underestimation of the number of medication errors. In particular, rates of reporting are influenced by local organisational culture and awareness, and are much higher from secondary care. In addition, it is only mandatory for NHS organisations to report incidents leading to death or severe harm to the national NRLS system. Reports from patients and carers are generally not included. Incident reports are often submitted before completion of a local investigation and hence there may be missing data, especially on contributory factors. Therefore, many reports did not contain sufficient information to determine whether or how guidelines contributed to errors. Furthermore, the level of harm resulting from the incident may not have been clear at the time of report, hence NRLS database reports may relate to actual or potential harm based only on the judgement of the reporter.

It is likely that the initial database search missed some relevant reports. An inductive approach to this free-text field search, with additional search terms identified from the results of initial searches, might have increased the sensitivity of this stage. The fact that so many errors were related to guidelines, despite these limitations, strengthens our finding that guidelines are an important area to address in medication safety.

Another limitation was the relatively low interrater reliability for coding to the stages of the HTA process. This may also have been due to the limited level of information in the reports. As a result of this, findings need to be interpreted with some caution. As only the first of a series of step discrepancies occurring in one incident was coded, any chains of discrepancies were not recorded. Finally, the database relates to England and Wales only, therefore it is uncertain as to how far the findings are generalisable to other countries.