Abstract
Objective:
Adverse drug events (ADEs) are drug-related events which continue to pose serious challenges to the safety of patients. There are a number of ways to monitor ADEs, and the use of indictors to screen them provides an alternative method for detecting them. This method helps to assess the safety of drugs by the manual record review technique. The aim of this work was to develop a list of indicators to use in medical units of the study hospital to identify ADEs.
Setting:
Tertiary care teaching hospital in India.
Method:
An initial list of ADE indicators based on published literature was developed by a panel of three experts. The list of indicators was subjected to review by a Delphi panel of five members. The Delphi panel reviewed the list of valid indicators and also suggested an addition of new indicators. The final list of indicators was used to review 100 previously documented ADE case reports. The case reports were screened for the presence of any of the indicators from the list. Parameters studied included number of indicators per case report and the most used indicators.
Results:
From the literature, a 72 item indicator list was initially prepared which was further narrowed down to a list of 63 items. The Delphi panel conducted a review with these 63 items. At the end of review, and after addition and deletion of indicators, a 49 item indicator list was finalized. When this list of indicators was used for the review of ADE case reports, 42 indicators were identified. On average, three indicators were present in the reviewed case reports.
Conclusion:
An indicator list was developed for identification of ADEs in the study setup. The relevance of this indicator list was demonstrated by the presence of these indicators in the previously documented ADE reports. This is the first study from India to report on the development of ADE indicators, which might provide an alternative method to detecting ADEs in the setup of future studies.
Introduction
An adverse drug event (ADE) is defined as “an injury resulting from medical intervention related to drugs”.Citation1 ADEs continues to be a serious challenge for the safety of patients. A significant number of ADEs are preventable in nature, and therefore this represents an avoidable burden on health care.Citation2 ADEs are monitored in a clinical setup using a number of methods like case reports, spontaneous reporting systems, intensive event recording, case-control studies, case-cohort studies, prospective cohort studies, incident reports, retrospective or concurrent chart reviews and observational studies.Citation3–Citation5 Each methodology has its own advantages and disadvantages.Citation6
An indicator is a clue that helps a health care organization to identify adverse events and assess the overall harm that occurs from medical care within that organization.Citation7 This methodology is based on identifying and addressing errors that are highly associated with negative outcomes.Citation8,Citation9 Indicators offer an approach to standardizing error identification that may provide more consistent and accurate information than traditional error reporting systems.Citation10 This system was also used for identification of adverse events along with traditional chart audits, incident reporting, or voluntary reporting. There are a number of reports on implementing electronic triggers to screen hospital records for the occurrence of ADEs.Citation11,Citation12
India is a developing country which is a member of the World Health Organization-run pharmacovigilance program. The pharmacovigilance in this country is still in its infancy.Citation13 ADE monitoring is carried out sporadically, and studies have reported that under-reporting is common in many of the study sites.Citation14–Citation16 This study was carried out in a tertiary care teaching hospital in South India. The ADE monitoring program was initiated in the current setup around a decade ago, but the level of participation of clinicians in this program is low.Citation17 It was planned to use indicators to identify ADEs in the current setup. For this purpose there was a need to develop a list of indicators specific for this setup. The present work was aimed to develop an indicator list based on available literature and modify it suitably with the help of a Delphi panel review and review of adverse event case reports.
Methodology
Development of indicators list
An initial list of ADE indicators was prepared based on published literature.Citation7,Citation18–Citation23 These indicators were reviewed by a panel of three experts (two clinical pharmacists and a clinician). The indicators which were relevant to the study setup were selected. The indicators relevant to general medical practice were kept in the list, whereas the indicators related to other specialties like psychiatry, intensive care unit (ICU), and surgery, were deleted. The review team collectively decided on whether to keep or delete a particular indicator from the list. This exercise was carried out to condense the list, so that the Delphi panel could work on it for the development of a final set of indicators.
Delphi panel review
A Delphi panel was formed with three clinicians and two clinical pharmacists. The members evaluated the indicator list anonymously and scored it. The panel members rated each item on the list on a Likert scale which represented a score from 1 to 5. During this review panel members were asked to suggest any additional indicators which could be added to the list. At the end of the first review, the scores were summarized and this was presented to the panel members along with their own scores. In the second review, panel members were encouraged to reassess their opinion in light of scores given by other members. Additional indicators were added to the list for review. After the second review, the mean score for each item was calculated. The mean score of 3 and above, out of 5, was considered as criteria for inclusion into the list. For the newly added indicators, one more review was conducted and mean scores were calculated. The final comprehensive list was divided into four categories, namely: (1) abnormal changes in clinical condition, (2) changes in patient care process, (3) drug-related alterations, (4) changes in lab investigations. (–)
Table 1 Indicators of abnormal change in clinical condition of patients
Table 2 Indicators of change in patient care process
Table 3 Indicators of drug-related alterations
Table 4 Indicators of lab investigation
After the preparation of a comprehensive list of indicators, they were used to screen previously identified and documented ADE case reports. A set of 100 previously documented ADE reports were randomly picked from the documented database. These adverse events were identified by clinical pharmacists from medicine wards during their rounds with clinicians. These reports contain complete details of the case which included medical history, diagnosis, lab investigations, therapy and ADE. Reports were reviewed for the presence of any indicators from the prepared list. The following four factors were then assessed: mean number of indicators per case report, commonly identified indicators, total number of identified indicators, and indicators that were not identified in any of the case reports.
Results
Screening by expert panel
From the literature, 72 indicators were selected for the list. The expert panel conducted a review of indicators. Items were added to the list based on the relevance of indicators for the internal medicine department and the utility of specific indicators. Indicators like ‘hospital visit due to depression or other psychiatric illness due to drug treatment or lack of monitoring’ was removed since such cases are usually presented to the psychiatry department and do not come under the general medicine department. Specific indicators like theophylline toxicity were removed because the use of theophylline is less common and its monitoring is not carried out. Indicators like toxicity of individual antiepileptic drugs such as phenytoin, carbamazepine, and sodium valproate were combined as ‘drug toxicity’. An indicator on long term use of codeine and acetaminophen for pain relief resulting in broken bones was removed since such a practice of using codeine for pain relief is not common in this setup. Indicators on gastritis and upper intestinal bleeding due to many different drugs and factors were reduced to two indicators. Many indicators were recommended to be deleted since their prevalence was thought to be low for this setup. Some indicators were combined with others since they were similar. At the end of the review, the list was modified to include 63 indicators.
Delphi panel review
The Delphi panel reviewed the indicator list for its utility. Five reviewers independently reviewed the list and rated them on a scale of 1 to 5. At the end of the first review, 22 out of 63 items in the list were rated less than 3 points and were subsequently eliminated. Eight new indicators were suggested by the members of Delphi panel. In the second review a total of 71 items were included in the list. The panel members were asked to rate all of the items. At the end of the second review, a total of 49 indicators received scores above 3. The results were again presented to the panel members with their scores against the scores of other team members for the third review. The third review did not alter the scores, 49 were rated above 3 points, and were included in the list.
Assessment of documented adverse event reports
A total of 42 indicators were identified in previous ADE case reports. Each reviewed case report had an average of three indicators from the list. Seven indicators could not be identified in any of the reported case records. Indicators which were most frequently identified from the reports were studied (). Abrupt drug withdrawal was the most common indicator identified in the reports, followed by repeat requests for laboratory tests, and use of antihistamine/steroids for the management of drug allergies. Drug induced pyrexia, edema, raised serum creatinine, and tremors were among the least identified indicators in reviewed reports.
Table 5 Most used indicators
Discussion
This report describes the development of ADE indicators in the current setup. This study used a team of clinicians and pharmacists to review the developed ADE indicators. The Delphi technique, which has been used in a number of previous studies, was used as a method of assessing the developed indicator list.
An initial list of 71 indicators selected from the literature was considered unmanageable, and after the Delphi panel review, the number of indicators was reduced to 49. In a study by Matlow et al on the development of trigger tools for pediatrics, they reported that 94 indicators were initially selected by a review committee. This list was considered as not practical for routine use, and was subsequently reduced to a manageable list of 40 indicators.Citation19 An indicator list containing a reasonably limited number of items is preferable since it reduces the burden on case record reviewers.
Abrupt withdrawal of drugs was identified most frequently as an indicator in the records. Since this is the first step in management of any drug-related adverse event, it could be found in many of the previously documented adverse event reports. Another commonly identified indicator was frequent requests for a specific lab investigation. Repeat requests for a particular investigation signifies a certain level of complication in the management of the patient’s condition, and might be associated with drug-related adverse events.
The indicator list was classified under four major categories: abnormal clinical changes, change in patient care, laboratory investigation-related, and drug/antidote-related. Among these four classes of indicators abnormal clinical changes included 22 indicators. This showed the preference of reviewers for the indicators which can identify adverse events based on the data available from patient progress charts and follow-up. Changes in patient care and lab investigations were the other important group of indicators considered for identifying ADEs (10 each). In contrast to a study published by Handler et al in which the medication concentration signals were considered as important, abnormal clinical changes were considered as important indicators in this study.Citation24 In this study, even when toxicity was suspected for a drug, estimation of drug levels was not carried out routinely because of economic considerations, and clinicians mostly rely on clinical signs and symptoms to assess toxicity.
Morris and Cantril validated drug-related morbidity indicators developed in the United States and United Kingdom, and studied differences between the two setups. They reported that indicators used in the USA lacked relevance to the UK. They attributed this to the difference in clinical practice and philosophical view points of professional practice. But they concluded that if suitable validation processes can be developed, indicators from one setup can act as a starting point for another setup.Citation22 The current work used indicators reported from various studies and attempted to validate such indicators for the study setup. This exercise gave insight into the viewpoints of health care professionals in the study center. The methodology of using specific triggers or indicators offers flexibility in using this system for a variety of health care systems. The indicators can be modified suitably according to individual setup.Citation7 Several institutions have used this approach in their setup and have reduced harm up to 50%. Even though this method itself may not result in improvement in prevention of adverse events concerned, it provides a good platform for any organization which attempts to reduce adverse events. Record review using indicators might provide a better chance of detecting ADEs compared with many other commonly used methods like voluntary reporting, intensive monitoring, and reporting of summary data. Use of this technique is also more economical when compared to other approaches. There are few limitations in this study which need to be considered. Even though indicators developed for one setup could be adopted for another setup, indicators adopted from a predominantly Western setup may not have relevance in the Indian setting. Unless the indicators are assessed by using them in the record review, the list might not reflect the useful indicators relevant for the current setup. Further validation is needed for this indicator list by actually using it for adverse event screening from the medical records.
Conclusion
The current work resulted in the development of an indicator list for identification of adverse events in the current setup. The list was prepared using the expert review and Delphi panel review. The final list contained a total of 49 indicators. The relevance of this indicator list was demonstrated by the presence of these indicators in the previously documented ADE case reports. This is the first study from India to report on the development of indicators, and this might provide an alternative method to detect ADEs in the studied health care setting.
Acknowledgements
The first author acknowledges the Indian Council of Medical Research for the fellowship support. The authors would like to acknowledge all health care professional of Kasturba Hospital, Manipal University and staff of Department of Pharmacy Practice for the support and encouragement extended for this work.
Disclosure
The authors report no conflicts of interest in this work.
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