The aim to compare various sources of the pharmacotherapy safety information in the outpatient register.Materials and methods. The original questionnaire included several questions for assessing information about patients’ knowledge of the concept of AEs of drug therapy, awareness of the possibility of drugs’ AEs, how often patients read the instructions for drugs and actions of patients in cases of AEs occurrence. Adverse events appearance were noted by the patients themselves in questionnaire and by doctors when completing the IRCs for the period from September 1. 2017 to May 31. 2018 are compared.Results. Of the 162 patients who answered the questions in the original questionnaire, there were 80 women and 82 men. 112 patients were observed by doctors regularly (at least 1 time per year), 16 people visited doctors 1 time in 1–2 years, 14 people were with a doctor more than 2 years ago, in 18 patients information on the regularity of observation by doctors is not indicated were. According to the questionnaire, the majority of patients (145 (89.5 %)) were familiar with information about the possibility of developing side effects of drugs, and 125 (86.2 %) people received this information from their doctor, 19 (13.1 %) noted that the doctor did not inform them about this. Only 6 patients did not know anything about AE pharmacotherapy. As the questionnaire showed, most patients get acquainted with the instructions for the prescribed medications. Comparison of data from the IRCs and questionnaires revealed more frequent registration of AE by doctors; however, there was an incomplete coincidence of information about the presence of AE from different sources.Conclusion. Using data from the retrospective-prospective registry with obtaining information about adverse events from doctors in combination with simultaneous patients questionare could get more complete information about safety of pharmacotherapy. At the same time solution to the problem of farmacotherapy safety lives in optimizing the doctor–patient relationship.

Literature monitoring is a complicated aspect of pharmacovigilance. The guidelines on good practice of pharmacovigilance of the Eurasian Economic Union recommend the using of a biomedical reference database containing the maximum number of sources for the monitored drugs, which necessitates the selection of such a database. The aim of the paper is to compare the coverage and functionality of international databases of medical publications recommended for monitoring literature within pharmacovigilance in terms of coverage and functionality. The paper analyzes the coverage and presents the comparison of the results of the search in the databases Embase®, MEDLINE® and eLibrary for 35 drugs. It have been shown that the search in the Embase® database provides the maximum number of sources. In addition, the paper shows the applicability special PV Wizard functionality which facilitate the building of search strategies with high recall, sensitivity and compliance.

Introduction Adverse drug reactions (ADRs) are associated with significant health-related and financial burden, and multiple sources are currently utilized to actively discover them. Social media has been proposed as a potential resource for monitoring ADRs, but drug-specific analytical studies comparing social media with other sources are scarce. Objectives Our objective was to develop methods to compare ADRs mentioned in social media with those in traditional sources: the US FDA Adverse Event Reporting System (FAERS), drug information databases (DIDs), and systematic reviews. Methods A total of 10,188 tweets mentioning adalimumab collected between June 2014 and August 2016 were included. ADRs in the corpus were extracted semi-automatically and manually mapped to standardized concepts in the Unified Medical Language System. ADRs were grouped into 16 biologic categories for comparisons. Frequencies, relative frequencies, disproportionality analyses, and rank ordering were used as metrics. Results There was moderate agreement between ADRs in social media and traditional sources. “Local and injection site reactions” was the top ADR in Twitter, DIDs, and systematic reviews by frequency, ranked frequency, and index ranking. The next highest ADR in Twitter—fatigue—ranked fifth and seventh in FAERS and DIDs. Conclusion Social media posts often express mild and symptomatic ADRs, but rates are measured differently in scientific sources. ADRs in FAERS are reported as absolute numbers, in DIDs as percentages, and in systematic reviews as percentages, risk ratios, or other metrics, which makes comparisons challenging; however, overlap is substantial. Social media analysis facilitates open-ended investigation of patient perspectives and may reveal concepts (e.g. anxiety) not available in traditional sources.

We performed a systematic review to assess whether we can quantify the underreporting of adverse events (AEs) in the published medical literature documenting the results of clinical trials as compared with other nonpublished sources, and whether we can measure the impact this underreporting has on systematic reviews of adverse events. Studies were identified from 15 databases (including MEDLINE and Embase) and by handsearching, reference checking, internet searches, and contacting experts. The last database searches were conducted in July 2016. There were 28 methodological evaluations that met the inclusion criteria. Of these, 9 studies compared the proportion of trials reporting adverse events by publication status. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies. A total of 11 studies compared the numbers of adverse events in matched published and unpublished documents. The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%. Within these 11 studies, 24 comparisons of named adverse events such as death, suicide, or respiratory adverse events were undertaken. In 18 of the 24 comparisons, the number of named adverse events was higher in unpublished than published documents. Additionally, 2 other studies demonstrated that there are substantially more types of adverse events reported in matched unpublished than published documents. There were 20 meta-analyses that reported the odds ratios (ORs) and/or risk ratios (RRs) for adverse events with and without unpublished data. Inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in 15 of the 20 pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases. The main limitations of this review are that the included case examples represent only a small number amongst thousands of meta-analyses of harms and that the included studies may suffer from publication bias, whereby substantial differences between published and unpublished data are more likely to be published. There is strong evidence that much of the information on adverse events remains unpublished and that the number and range of adverse events is higher in unpublished than in published versions of the same study. The inclusion of unpublished data can also reduce the imprecision of pooled effect estimates during meta-analysis of adverse events.

Case report publications introduce new information into the current body of medical information and provide trainees with an opportunity to develop skills that enhance patient care. However, opportunities for publication are limited because journals often have other editorial priorities and some journals do not want to publish articles that might decrease their impact factors. Using PubMed and Google Scholar, we identified the case report articles published by our residents who completed training between 2008 and 2013. Sixty-one residents published 55 case reports and/or letters. Twenty-five of these publications had 87 citations in the years of publication and up 5 years after publication. Most of these citations occurred in other case reports (36) or in review articles (24). In conclusion, publishing case reports by residents has important benefits for the individual resident and the residency program and provides another resource for medical care.

A diverse range of study designs (e.g. case-control or cohort) are used in the evaluation of adverse effects. We aimed to ascertain whether the risk estimates from meta-analyses of case-control studies differ from that of other study designs. Searches were carried out in 10 databases in addition to reference checking, contacting experts, and handsearching key journals and conference proceedings. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from case-control studies could be directly compared with the pooled estimate for the same adverse effect arising from other types of observational studies. We included 82 meta-analyses. Pooled estimates of harm from the different study designs had 95% confidence intervals that overlapped in 78/82 instances (95%). Of the 23 cases of discrepant findings (significant harm identified in meta-analysis of one type of study design, but not with the other study design), 16 (70%) stemmed from significantly elevated pooled estimates from case-control studies. There was associated evidence of funnel plot asymmetry consistent with higher risk estimates from case-control studies. On average, cohort or cross-sectional studies yielded pooled odds ratios 0.94 (95% CI 0.88–1.00) times lower than that from case-control studies. Empirical evidence from this overview indicates that meta-analysis of case-control studies tend to give slightly higher estimates of harm as compared to meta-analyses of other observational studies. However it is impossible to rule out potential confounding from differences in drug dose, duration and populations when comparing between study designs.

The aim of this study was to examine the effects of acupuncture on urinary incontinence and to discuss why these acupoints were selected. Seven databases were searched for any randomized controlled trials (RCTs) that investigated the use of acupuncture or acupressure as a treatment for urinary incontinence, and the Cochrane risk of bias tool was utilized to evaluate the risk of bias in each study. Four RCTs met all the inclusion criteria. The results from the selected RCTs failed to demonstrate any statistically significant improvements in urinary incontinence, although acupuncture or acupressure did exhibit favorable effects on overactive bladder symptoms and quality of life, in comparison with other conventional therapies. There have been limited results supporting acupuncture or acupressure as an effective treatment method for urinary incontinence; therefore, further RCTs are required to confirm the effectiveness of acupuncture or acupressure in the treatment of urinary incontinence.

Randomized controlled trials are the principal means of establishing the efficacy of drugs. However pre-marketing trials are limited in size and duration and exclude high-risk populations. They have limited statistical power to detect rare but potentially serious adverse events in real-world patients. We summarize the principal methodological challenges in the reporting, analysis and interpretation of safety data in clinical trials using recent examples from systematic reviews. These challenges include the lack of an evidentiary gold standard, the limited statistical power of randomized controlled trials and resulting type 2 error, the lack of adequate ascertainment of adverse events and limited generalizability of trials that exclude high risk patients. We discuss potential solutions to these challenges. Evaluation of drug safety requires careful examination of data from heterogeneous sources. Meta-analyses of drug safety should include appropriate statistical methods and assess the optimal information size to avoid type 2 errors. They should evaluate outcome reporting biases and missing data to ensure reliable and accurate interpretation of findings. Regulatory and academic partnerships should be fostered to provide an independent and transparent evaluation of drug safety.

Background: For all medications, there is a trade-off between benefits and potential for harm. It is important for patient safety to detect drug-event combinations and analyze by appropriate statistical methods. Mefloquine is used as chemoprophylaxis for travelers going to regions with known chloroquine-resistant Plasmodium falciparum malaria. As such, there is a concern about serious adverse events associated with mefloquine chemoprophylaxis. The objective of the present study was to assess whether any signal would be detected for the serious adverse events of mefloquine, based on data in clinicoepidemiological studies. Materials and methods: We extracted data on adverse events related to mefloquine chemoprophylaxis from the two published datasets. Disproportionality reporting of adverse events such as neuropsychiatric events and other adverse events was presented in the 2 × 2 contingency table. Reporting odds ratio and corresponding 95% confidence interval [CI] data-mining algorithm was applied for the signal detection. The safety signals are considered significant when the ROR estimates and the lower limits of the corresponding 95% CI are ≥2. Results: Two datasets addressing adverse events of mefloquine chemoprophylaxis (one from a published article and one from a Cochrane systematic review) were included for analyses. Reporting odds ratio 1.58, 95% CI: 1.49–1.68 based on published data in the selected article, and 1.195, 95% CI: 0.94–1.44 based on data in the selected Cochrane review. Overall, in both datasets, the reporting odds ratio values of lower 95% CI were less than 2. Conclusion: Based on available data, findings suggested that signals for serious adverse events pertinent to neuropsychiatric event were not detected for mefloquine. Further studies are needed to substantiate this.

Objective—To critically evaluate and summarize available information on the safety of potassium bromide in dogs. Design—Systematic review. Sample—111 references reporting safety information relevant to potassium bromide published between 1938 and 2011. Procedures—PubMed searches without date limitations were conducted with the terms “potassium bromide” and “sodium bromide” in December 2009 and October 2011. Additional articles were identified through examination of article reference lists and book chapters on seizures in dogs and pharmacology. Results—Reversible neurologic signs were the most consistently reported toxicoses and were generally associated with adjunctive potassium bromide treatment or high serum bromide concentrations. Dermatologic and respiratory abnormalities were rare in dogs. Insufficient information was available to assess the effects of potassium bromide on behavior or to determine the incidence of vomiting, weight gain, polyphagia, pancreatitis, polyuria, polydipsia, or reproductive abnormalities associated with potassium bromide administration. Evidence suggested that administration of potassium bromide with food may alleviate gastrointestinal irritation and that monitoring for polyphagia, thyroid hormone abnormalities, and high serum bromide concentrations may be beneficial. Conclusions and Clinical Relevance—Results suggested that potassium bromide is not an appropriate choice for treatment of every dog with seizures and that practitioners should tailor therapeutic regimens and clinical monitoring to each dog. Abrupt dietary changes or fluid therapy may compromise seizure control or increase the likelihood of adverse events. Availability of an appropriately labeled, approved potassium bromide product could provide better assurance for veterinarians and their clients of the quality, safety, and effectiveness of the product for veterinary use.

There is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies. Searches were carried out in ten databases in addition to reference checking, contacting experts, citation searches, and hand-searching key journals, conference proceedings, and Web sites. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from RCTs could be directly compared, using the ratio of odds ratios, with the pooled estimate for the same adverse effect arising from observational studies. Nineteen studies, yielding 58 meta-analyses, were identified for inclusion. The pooled ratio of odds ratios of RCTs compared to observational studies was estimated to be 1.03 (95% confidence interval 0.93–1.15). There was less discrepancy with larger studies. The symmetric funnel plot suggests that there is no consistent difference between risk estimates from meta-analysis of RCT data and those from meta-analysis of observational studies. In almost all instances, the estimates of harm from meta-analyses of the different study designs had 95% confidence intervals that overlapped (54/58, 93%). In terms of statistical significance, in nearly two-thirds (37/58, 64%), the results agreed (both studies showing a significant increase or significant decrease or both showing no significant difference). In only one meta-analysis about one adverse effect was there opposing statistical significance. Empirical evidence from this overview indicates that there is no difference on average in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational studies. This suggests that systematic reviews of adverse effects should not be restricted to specific study types. Please see later in the article for the Editors' Summary

While systematic reviews and meta-analyses are at the top of the evidence hierarchy, most of the methodology has focused on assessing treatment benefit. Hence, we propose a structured framework for the initial steps of searching and identifying relevant data sources so that adverse effects can be evaluated in a comprehensive, unbiased manner. The unique methodological challenges stem from the difficulties of addressing diverse outcomes encompassing common, mild symptoms to rare, fatal events. Retrieval of the most appropriate studies should be specifically tailored to fit the nature of the adverse effects, according to the primary objective and study question. In our framework, the structure of the review takes different forms depending on whether the main aim is on scoping/hypothesis generation, or evaluating statistically the magnitude of risk (hypothesis testing), or clarifying characteristics and risk factors of the adverse effect. The wide range of data sources covering adverse effects all have distinct strengths and limitations, and selection of appropriate sources depends on characteristics of the adverse effect (e.g. background incidence and effect size of the drug, clinical presentation, time of onset after drug exposure). Reviewers need to retrieve particular study designs that are most likely to yield robust data on the adverse effects of interest, rather than rely on studies that cannot reliably detect adverse effects, and may yield ‘false negatives’. Type II errors (a particular problem when evaluating rare adverse effects) can lull us into a false sense of security (e.g. wrongly concluding that there was no significant difference in harm between drug and control, with the drug erroneously judged as safe). Given the rapid rate at which methodological improvements occur, this proposed framework is by no means definitive, but aims to stimulate further debate and discussion amongst the pharmacoepidemiological and systematic review communities to reach a common consensus on the best methods.

To assess the impact of including unpublished data on adverse effects in systematic reviews.We carried out a systematic review of methodological evaluations that compared the quantitative reporting of adverse effects data between published and unpublished sources, in particular, the frequency, rate, or risk of reported adverse effects. Included studies were sought from 10 databases as well as by checking references, handsearching, searching citations, and contacting experts.We identified 6,218 potential articles yielding 10 relevant methodological evaluations. One evaluation found that adverse effects were reported more often in unpublished trials. For anecdotal case reports, two evaluations found a higher frequency of unpublished cases, whereas one study identified a greater number of published cases. Another evaluation indicated that differences in frequency of published and unpublished case reports were topic dependent. A comparison of relative risk estimates from five studies suggested no major systematic variation in risk estimates from published and unpublished studies.Inclusion of unpublished studies can provide additional adverse effects information and more precise risk estimates. However, there is insufficient evidence to indicate whether inclusion of unpublished studies has a major influence on the pooled risk estimates in meta-analyses of adverse effects.

Conclusions Establishing peritoneal ports with the trocarless TVC is feasible, reproducible, and seems to be highly adoptable.

Comparative effectiveness reviews (CERs) are systematic reviews that evaluate evidence on alternative interventions to help clinicians, policy makers, and patients make informed treatment choices. Reviews should assess harms and benefits to provide balanced assessments of alternative interventions. Identifying important harms of treatment and quantifying the magnitude of any risks require CER authors to consider a broad range of data sources, including randomized controlled trials (RCTs) and observational studies. This may require evaluation of unpublished data in addition to published reports. Appropriate synthesis of harms data must also consider issues related to evaluation of rare or uncommon events, assessments of equivalence or noninferiority, and use of indirect comparisons. This article presents guidance for evaluating harms when conducting and reporting CERs. We include suggestions for prioritizing harms to be evaluated, use of terminology related to reporting of harms, selection of sources of evidence on harms, assessment of risk of bias (quality) of harms reporting, synthesis of evidence on harms, and reporting of evidence on harms.

The effectiveness of acupuncture in the case of premenstrual syndrome (PMS) is not fully understood. To assess the effectiveness and adverse effects of acupuncture for the symptomatic treatment of PMS from randomised controlled trials (RCTs). Electronic databases, including English, Korean, Japanese and Chinese, were systematically searched up to January 2009 with no language restrictions. RCTs comparing acupuncture with control investigating acupuncture for PMS were considered. Study collection and quality assessment were performed by two reviewers using the criteria described in the Cochrane Handbook. Nine studies were systematically reviewed. Only two of the nine trials reported details regarding sequence generation and allocation concealment. Four studies reported a significant difference in reduction of PMS symptoms for acupuncture treatment compared with pharmacological treatment. Two studies reported the improvements in primary symptoms within the acupuncture and herbal medications groups compared with baseline. Only two RCTs reported information regarding acupuncture-related adverse events, which included one case of a small subcutaneous haematoma. Although the included trials showed that acupuncture may be beneficial to patients with PMS, there is insufficient evidence to support this conclusion due to methodological flaws in the studies, including unknowns in sequence generation, concealment of allocation, blinding and outcome measures.

Peer reviewed article authored by (Mariam Molokhia, Shivani Tanna, Derek Bell). Read article or submit your manuscript for publishing.

Purpose. A case of amiodarone-induced neurotoxicity is reported.

SUMMARY Background: Data on medication adverse effects (AEs) in chronic heart failure (CHF) are primarily based on results from clinical trials. Little is known about AEs perceived by CHF patients in daily practice and how patients deal with these sub- jective AEs. Aims: To describe the scope and nature of perceived AEs of CHF patients, their coping strategies and the relationship of perceived AEs to medica- tion, patient characteristics and quality of life. Methods: This cross-sectional observational study included a sample of 680 patients previously hospitalised for CHF. Perceived AEs and coping strategies were collected by interviews based on a structured questionnaire. Medication and clinical information were collected by chart review. Results: Of the 670 CHF patients completing the questionnaire, 17% reported at least one AE. In total, 186 AEs were reported of which 15% could not be linked to any medication. Nausea (4%), dizziness (4%), itches (3%) and rash (3%) were the most prevalent. The drug associated with the highest AE rate was pravastatin (27%). On average, more than five different drugs could be related to the AEs headache, dizziness and nausea. Patients reporting AEs had a lower general health perception, younger age and were more often using antiar- rhythmic drugs. Of patients experiencing AEs, 69% conferred with their doctor, 24% reported having done nothing in reaction and 2% discontinued their medica- tion without discussing it with the doctor. Conclusion: Adverse effects are fre- quently perceived by CHF patients, but they are difficult to recognise and manage in daily practice. What's known • Data on drug safety are primarily based on the results from clinical trials, where the patients included often have less comorbidity and comedication than the patients using the drugs in everyday practice. • It has been estimated that at least 5-10% of patients in clinical trials discontinue use of placebo because of perceived adverse effects (AEs).

The central theme of the Institute of Medicine report on the US drug safety system was the need for a life cycle approach to drug evaluation: both the benefits and the risks need to be evaluated and integrated during the entire market life of a drug.¹ The Food and Drug Administration Amendments Act of 2007 also called on the agency to improve its methods of communicating risks and benefits to patients and physicians. The Institute of Medicine recommendation to “develop and continually improve a systematic approach to risk-benefit analysis for use throughout the [Food and Drug Administration] in the preapproval and postapproval settings” specifically acknowledges the need for and the challenges of the development of new methods of combining evidence about risks and benefits.¹

The objective of systematic reviews of the efficacy and safety of interventions is to determine in an unbiased and objective manner whether a proper balance between risks and benefits exists. However, systematic reviews including many Cochrane reports often get criticized for having an overly narrow focus on randomized controlled trials leading to results that have low applicability and do not adequately reflect the underlying risk-benefit profiles. The objective of this paper is to encourage the discussion on two important issues frequently covered inadequately in Cochrane reports: the assessment of adverse effects and the applicability of results. It also strives to outline approaches for improving the comprehensiveness and usability of Cochrane reports by including observational evidence for adverse effects assessment on a regular basis and by putting more emphasis on factors that determine the applicability of findings.

Background As every healthcare intervention carries some risk of harm, clinical decision making needs to be supported by a systematic assessment of the balance of benefit to harm. A systematic review that considers only the favourable outcomes of an intervention, without also assessing the adverse effects, can mislead by introducing a bias favouring the intervention. Much of the current guidance on systematic reviews is directed towards the evaluation of effectiveness; but this differs in important ways from the methods used in assessing the safety and tolerability of an intervention. A detailed discussion of why, how and when to include adverse effects in a systematic review, is required. Methods This discussion paper, which presupposes a basic knowledge of systematic review methodology, was developed by consensus among experienced reviewers, members of the Adverse Effects Subgroup of The Cochrane Collaboration, and supplemented by a consultation of content experts in reviews methodology, as well as those working in drug safety. Results A logical framework for making decisions in reviews that incorporate adverse effects is provided. We explore situations where a comprehensive investigation of adverse effects is warranted and suggest strategies to identify practicable and clinically useful outcomes. The advantages and disadvantages of including observational and experimental study designs are reviewed. The consequences of including separate studies for intended and unintended effects are explained. Detailed advice is given on designing electronic searches for studies with adverse effects data. Reviewers of adverse effects are given general guidance on the assessment of study bias, data collection, analysis, presentation and the interpretation of harms in a systematic review. Conclusion Readers need to be able to recognize how strategic choices made in the review process determine what harms are found, and how the findings may affect clinical decisions. Researchers undertaking a systematic review that incorporates adverse effect data should understand the rationale for the suggested methods and be able to implement them in their review.

Drug-induced pancreatitis is estimated to be responsible for nearly 2% of cases of acute pancreatitis.1 Angiotensin-converting enzyme (ACE) inhibitors are some of the most widely prescribed medications. The occurrence of acute pancreatitis with several different ACE inhibitors including captopril,2–3 lisinopril,4–8 quinapril,9 ramipril,10–11perinodpril,12 enalapril13–17 has been...

This study aimed to assess the performance, in terms of sensitivity and precision, of different approaches to searching MEDLINE and EMBASE to identify studies of adverse effects. Five approaches to searching for adverse effects evidence were identified: approach 1, using specified adverse effects; approach 2, using subheadings/qualifiers; approach 3, using text words; approach 4, using indexing terms; approach 5, searching for specific study designs. The sensitivity and precision of these five approaches, and combinations of these approaches, were compared in a case study using a systematic review of the adverse effects of seven anti-epileptic drugs. The most sensitive search strategy in MEDLINE (97.0%) required a combination of terms for specified adverse effects, floating subheadings, and text words for 'adverse effects'. In EMBASE, a combination of terms for specified adverse effects and text words for 'adverse effects' provided the most sensitive search strategy (98.6%). Both these search strategies yielded low precision (2.8%). A highly sensitive search in either database requires a combination of approaches, and has low precision. This suggests that better reporting and indexing of adverse effects is required and that an effective generic search filter may not yet be feasible.

Objective To determine whether anecdotal reports of suspected adverse drug reactions are valuable early warning signals. Design Systematic literature survey Data sources We evaluated all case reports of adverse drug reactions published in 1997 in five medical journals. Reports were excluded if the adverse reaction had previously been described in earlier publications and was already listed in the product information of the drug reference source (the British National Formulary (BNF) or the Medicines Compendium). We used the Web of Knowledge Citation Index and Medline for 2003 to identify follow-up studies. Main outcome measures Primary: the number of suspected adverse reactions subjected to formal validation studies and the findings of these studies. Secondary: the number of instances in which the warning from the case report was incorporated into the product information. Results We evaluated 63 suspected adverse reactions and found that most (52/63, 83%) had not yet been subjected to further detailed evaluation. Data from controlled studies that supported the postulated link between the drug and the adverse event were available in only three cases. Of the 48 agents listed in the drug reference sources, details of the suspected reaction were subsequently added to the Medicines Compendium in 15 instances, and to the BNF in seven instances. In each case, only one reaction had been confirmed. Conclusions Published case reports of suspected adverse reactions are of limited value as suspicions are seldom subjected to confirmatory investigation. Furthermore, these alerts are not incorporated into drug reference sources in a systematic manner.