Research Pharmacist Research Articles

Real-World Data and Randomised Controlled Trials: The Salford Lung Study.

Traditional efficacy double-blind randomised controlled trials (DBRCTs) measure the benefit a treatment produces under near-ideal test conditions in highly selected patient populations; however, the behaviour of patients and investigators in such trials is highly controlled, highly compliant and adherent, and non-representative of routine clinical practice. Pragmatic effectiveness trials measure the benefit a treatment produces in patients in everyday “real-world” practice. Ideally, effectiveness trials should recruit patients as similar as possible to those who will ultimately be prescribed the medicine, and create freedom within the study design to allow normal behaviours of patients and healthcare professionals (HCPs) to be expressed. The Salford Lung Study (SLS) was a world-first, prospective, phase III, pragmatic randomised controlled trial (RCT) programme in patients with chronic obstructive pulmonary disease and asthma to evaluate the effectiveness of a pre-licensed medication (fluticasone furoate/vilanterol) in real-world practice using electronic health records and through collaboratively engaging general practitioners and community pharmacists in clinical research. The real-world aspect of SLS was unique, requiring careful planning and attention to the goals of maximising the external validity of the trials while maintaining scientific rigour and securing suitable electronic processes for proper interpretation of safety data. Key learnings from SLS that may inform the design of future pragmatic effectiveness RCTs include: (1) ensuring the trial setting and operational infrastructure are aligned with routine clinical care; (2) recruiting a broad patient population with characteristics as close as possible to patients in routine clinical practice, to maximise the generalisability and applicability of trial results; (3) ensuring that patients and HCPs are suitably engaged in the trial, to maximise the chances of successful trial delivery; and (4) careful study design, incorporating outcomes of value to patients, HCPs, policymakers and payers, and using pre-planned analyses to address scientifically valid research hypotheses to ensure robustness of the trial data.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-01192-1) contains supplementary material, which is available to authorized users.

Personal Experience of a Research Pharmacist in Industry—R&D in the Heisei Era

Personal Experience of a Research Pharmacist in Industry—R&D in the Heisei Era

Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients: a multicentre randomized superiority trial.

AimsMost cardiac surgery patients, with or without diabetes, develop perioperative hyperglycaemia, for which intravenous insulin is the only therapeutic option. This is labour‐intensive and carries a risk of hypoglycaemia. We hypothesized that preoperative administration of the glucagon‐like peptide‐1 receptor agonist liraglutide reduces the number of patients requiring insulin for glycaemic control during cardiac surgery.Materials and methodsIn this randomized, blinded, placebo‐controlled, parallel‐group, balanced (1:1), multicentre randomized, superiority trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomized to receive 0.6 mg subcutaneous liraglutide on the evening before surgery and 1.2 mg after induction of anaesthesia or matching placebo. Blood glucose was measured hourly and controlled using an insulin‐bolus algorithm. The primary outcome was insulin administration for blood glucose >8.0 mmol/L in the operating theatre. Research pharmacists used centralized, stratified, variable‐block, randomization software. Patients, care providers and study personnel were blinded to treatment allocation.ResultsBetween June 2017 and August 2018, 278 patients were randomized to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention‐to‐treat analyses (129 in the liraglutide group, 132 in the placebo group). In the liraglutide group, 55 (43%) patients required additional insulin compared with 80 (61%) in the placebo group and absolute difference 18% (95% confidence interval 5.9–30.0, P = 0.003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality or postoperative complications.ConclusionsPreoperative liraglutide, compared with placebo, reduces insulin requirements while improving perioperative glycaemic control during cardiac surgery.

Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients - A multicentre, prospective, randomised superiority trial

Introduction Most cardiac surgery patients, with or without diabetes, develop perioperative hyperglycaemia, for which intravenous insulin is the only therapeutic option. This is labour-intensive and carries a risk of hypoglycaemia. We hypothesised that preoperative administration of the glucagon-like peptide-1 receptor agonist liraglutide reduces the number of patients requiring insulin for glycaemic control during cardiac surgery. Methods In this randomised, blinded, placebo-controlled, parallel-group, balanced (1:1), multicentre randomised, superiority trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomised to receive 0·6 mg subcutaneous liraglutide on the evening before surgery and 1·2 mg after induction of anaesthesia or matching placebo. Blood glucose was measured hourly and controlled using an insulin-bolus-algorithm. The primary outcome was insulin administration for blood glucose above 8·0 mmol/L in the operating theatre. Research pharmacists used centralised, stratified, variable-block, randomisation software. Patients, care providers, and study personnel were blinded to treatment allocation. Results Between June 2017 and August 2018, 278 patients were randomised to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention-to-treat analyses (129 in the liraglutide group, 132 in the placebo group). In the liraglutide group 55 (43%) patients required additional insulin compared to 80 (61%) patients in the placebo group, absolute difference: 18% (95% CI 5·9–30·0, p = 0·003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group, see figure. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality, or postoperative complications. Discussion Preoperative liraglutide, compared to placebo, reduces insulin requirements while improving peri-operative glycaemic control during cardiac surgery.

Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomised clinical trial

Well designed, large comparative effectiveness trials assessing the efficacy of primary interventions for faecal incontinence are few in number. The objectives of this study were to compare different combinations of anorectal manometry-assisted biofeedback, loperamide, education, and oral placebo. In this randomised factorial trial, participants were recruited from eight clinical sites in the USA. Women with at least one episode of faecal incontinence per month in the past 3 months were randomly assigned 0·5:1:1:1 to one of four groups: oral placebo plus education only, placebo plus anorectal manometry-assisted biofeedback, loperamide plus education only, and loperamide plus anorectal manometry-assisted biofeedback. Participants received 2 mg per day of loperamide or oral placebo with the option of dose escalation or reduction. Women assigned to biofeedback received six visits, including strength and sensory biofeedback training. All participants received a standardised faecal incontinence patient education pamphlet and were followed for 24 weeks after starting treatment. The primary endpoint was change in St Mark's (Vaizey) faecal incontinence severity score between baseline and 24 weeks, analysed by intention-to-treat using general linear mixed modelling. Investigators, interviewers, and outcome evaluators were masked to biofeedback assignment. Participants and all study staff other than the research pharmacist were masked to medication assignment. Randomisation took place within the electronic data capture system, was stratified by site using randomly permuted blocks (block size 7), and the sizes of the blocks and the allocation sequence were known only to the data coordinating centre. This trial is registered with ClinicalTrials.gov, number NCT02008565. Between April 1, 2014, and Sept 30, 2015, 377 women were enrolled, of whom 300 were randomly assigned to placebo plus education (n=42), placebo plus biofeedback (n=84), loperamide plus education (n=88), and the combined intervention of loperamide plus biofeedback (n=86). At 24 weeks, there were no differences between loperamide versus placebo (model estimated score change -1·5 points, 95% CI -3·4 to 0·4, p=0·12), biofeedback versus education (-0·7 points, -2·6 to 1·2, p=0·47), and loperamide and biofeedback versus placebo and biofeedback (-1·9 points, -4·1 to 0·3, p=0·092) or versus loperamide plus education (-1·1 points, -3·4 to 1·1, p=0·33). Constipation was the most common grade 3 or higher adverse event and was reported by two (2%) of 86 participants in the loperamide and biofeedback group and two (2%) of 88 in the loperamide plus education group. The percentage of participants with any serious adverse events did not differ between the treatment groups. Only one serious adverse event was considered related to treatment (small bowel obstruction in the placebo and biofeedback group). In women with normal stool consistency and faecal incontinence bothersome enough to seek treatment, we were unable to find evidence against the null hypotheses that loperamide is equivalent to placebo, that anal exercises with biofeedback is equivalent to an educational pamphlet, and that loperamide and biofeedback are equivalent to oral placebo and biofeedback or loperamide plus an educational pamphlet. Because these are common first-line treatments for faecal incontinence, clinicians could consider combining loperamide, anal manometry-assisted biofeedback, and a standard educational pamphlet, but this is likely to result in only negligible improvement over individual therapies and patients should be counselled regarding possible constipation. Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health.

56-OR: Liraglutide for Perioperative Management of Hyperglycaemia in Cardiac Surgery Patients (GLOBE): A Multicentre, Prospective, Superiority Randomised Trial

Background: Most cardiac surgery patients develop perioperative hyperglycaemia requiring intravenous insulin therapy. This is labour-intensive and carries a risk of hypoglycaemia. We hypothesised that preoperative administration of the GLP-1 receptor agonist liraglutide would reduce the number of patients requiring insulin during cardiac surgery. Methods: In this randomised, blinded, placebo-controlled, parallel-group, balanced (1:1), superiority, multicentre randomised trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomised to receive 0·6 mg subcutaneous liraglutide on the evening before surgery and 1·2 mg after induction of anaesthesia, or matching placebo. Blood glucose was measured hourly and controlled using an insulin-bolus-algorithm. The primary outcome was insulin administration for blood glucose above 8·0 mmol/L in the operating theatre. Research pharmacists used centralised, stratified, variable-block, randomisation software. Patients, care providers, and study personnel were blinded to treatment allocation. Findings: Between June 2017 and August 2018, 278 patients were randomised to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention-to-treat analyses (liraglutide: 129, placebo: 132). In the liraglutide group, 55 patients (43%) required additional insulin compared to 80 patients (61%) in the placebo group, absolute difference: 18% (95% CI 5·9-30·0, p=0·003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality, or postoperative complications. Interpretation: Preoperative liraglutide reduces insulin requirements while improving peri-operative glycaemic control during cardiac surgery. Disclosure A.H. Hulst: Research Support; Self; Novo Nordisk A/S. B. Preckel: Research Support; Self; Novo Nordisk Inc. M.W. Hollmann: Consultant; Self; Eurocept BV. Other Relationship; Self; CSL Behring. J. DeVries: Advisory Panel; Self; Novo Nordisk A/S. Employee; Self; Profil Institute for Metabolic Research. Speaker's Bureau; Self; Novo Nordisk A/S. J. Hermanides: Consultant; Self; Julius Clinical (CRO). Research Support; Self; Novo Nordisk A/S. Funding Novo Nordisk A/S

Problems with Advertisements for Health Foods

We have been studying the way advertisements for medicines have been monitored by the Health, Labour and Welfare Sciences Research Grants. In the last fiscal year, we identified products that were being advertised to general consumers, such as OTC drugs and designated quasi-drugs, and made recommendations to the Ministry of Health, Labour and Welfare on the methods of advertisement. Members of our research group, including physicians, pharmacists, and consumers, pointed out that advertisements for so-called health foods and foods with functional claims were much more unregulated than those for drugs, including OTC drugs. Thus, this fiscal year, we decided to focus on health foods. Advertisements for health foods are regulated by the Health Promotion Act and the Act against Unjustifiable Premiums and Misleading Representations; moreover, in many cases, cautions are issued by the Consumer Affairs Agency or prefectures. Several studies also reported health damage in patients who, because of their belief in advertisements, intentionally discontinued treatment or missed the opportunity to receive appropriate medical treatment. Here, we report inappropriate advertisements for health foods that may cause health hazards.

Vitamin A treatment for severe sepsis in humans; a prospective randomized double blind placebo-controlled clinical trial

To test the benefits of Vitamin A treatment in patients with sepsis on length of time in ICU, days on ventilator, days on intravenous blood pressure support and 28-day mortality. The trial was prospective, randomized and double-blind. As part of a larger sepsis trial, 63 patients with sepsis were randomized to receive either 100,000IU of Vitamin A intramuscular or placebo over 7-days. Data analysis was by ANOVA with two tailed test and p<0.05 as significant. The mean age was 51±2 (mean±SEM) with 54% female. Groups were well matched with regards to APACHE III score, WBC count, and incidence of bacteremia. In addition, all patients had an ACTH stimulation test using 250mcg of ACTH IV and serum cortisol was measured at time 0, 30 and 60min. Baseline cortisol of 24.6±1mg/dl increased to 41±2mg/dl at 30min and 49±2at 60min. There was no significant difference between the groups. All cortisol responses were greater than 11.9mg/dl. Serum Vitamin A level was below normal in 54% of the patients. After randomization, 100,000IU of Vitamin A daily was given to 32 patients and blinded placebo was given daily to 32 patients for seven days. This was administered as a 1cc injection of either medication or placebo and was blinded from all but the research pharmacist. The number of days in the ICU was slightly, but not significantly reduced (p=0.39) by approximately 2 days in the Vitamin A treated patients. The average number of days on blood pressure agents and the day on ventilator were similar. The 28-day mortality rates were similar between the two groups (28 vs 34% placebo vs Vitamin A group). Seven days of high dose intramuscular Vitamin A treatment in patients with sepsis where approximately 50% were vitamin A deficient had no benefit in adults with sepsis.

Comparing the accuracy of medication order verification between pharmacists and a tech check tech model: A prospective randomised observational study.

Medication errors have the potential to cause significant harm and the final verification of dispensed medications is essential to patient safety. There is international evidence to demonstrate that trained pharmacy technicians can safely and accurately undertake the verification of medication orders in ward-based unit dose containers. There is a need for evaluation of pharmacy technician verification of medication orders in broader contexts including the hospital inpatient dispensary. To compare the accuracy of Accuracy Checking Pharmacy Assistants (ACPTs) to pharmacists when verifying inpatient medication orders within the hospital pharmacy setting. This 'real world' single-blinded study was conducted in the inpatient dispensary of a major tertiary hospital in Melbourne, Australia. Inpatient medication orders were randomly allocated to an ACPT or pharmacist for final verification, before being reviewed for accuracy by an independent research pharmacist blinded to study allocation. Errors identified by the reviewing pharmacist were documented and severity was assessed by an independent Medication Safety pharmacist. Between February and August 2014, three ACPTs verified 4718 items with 75 errors missed (1.59%), and twelve pharmacists verified 4194 items with 158 errors missed (3.77%). There was a statistically significant difference between both total and minor error rates, with pharmacists missing significantly more errors (total errors: p<0.0001; minor errors: 1.42 vs 3.53%; p<0.0001). There was no statistically significant difference in the rate of major errors missed by the two groups (0.17 vs 0.24%; p=0.48). This study is the first of its kind in the hospital dispensary setting, demonstrating that the overall accuracy of ACPTs was greater than pharmacists for verifying dispensed medication orders. ACPTs missed fewer minor and overall errors than pharmacists, indicating that trained pharmacy technicians can verify medication orders safely and accurately. This study provides support for the tech-check-tech model in the hospital setting.

AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial

SummaryBackgroundChloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria.MethodsWe did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 μL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964.FindingsBetween Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2–4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference −6·1%, 95% CI −14·7 to 2·4). Proportions cured were also similar between the groups in the intention-to-treat analysis (28 of 33, 84·8% for AQ-13 vs 31 of 33, 93·9% for artemether and lumefantrine; p=0·43) but the upper bound of the 95% CI exceeded the 15% non-inferiority margin (difference 9·1%, 95% CI −5·6 to 23·8).InterpretationThe per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine. By contrast, the intention-to-treat analysis, which included two participants who withdrew and three who were lost to follow-up from the AQ-13 group, did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures. Studies with more participants (and non-immune participants) are needed to decide whether widespread use of modified 4-aminoquinolones should be recommended.FundingUS Food and Drug Administration Orphan Product Development, National Institutes of Health, US Centers for Disease Control and Prevention, Burroughs-Wellcome Fund, US State Department, and WHO.

The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial

Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 μg of haemagglutinin per H1N1 vaccine strain, 17 μg of haemagglutinin per H3N2 vaccine strain, and 15 μg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat. Secondary immunogenicity outcomes are antibody titres at day 28 and percentages of seroconversion and seroprotection, all determined by haemagglutination inhibition antibody assay. The trial is completed and registered with ClinicalTrials.gov, number NCT02438423. Between June 23, 2015, and Sept 25, 2015, 100 participants were enrolled and randomly assigned to a group. There were no treatment-related serious adverse events, no treatment-related unsolicited grade 3 or higher adverse events, and no new-onset chronic illnesses. Among vaccinated groups (vaccine via health-care worker administered microneedle patch or intramuscular injection, or self-administered microneedle patch), overall incidence of solicited adverse events (n=89 vs n=73 vs n=73) and unsolicited adverse events (n=18 vs n=12 vs n=14) were similar. Reactogenicity was mild, transient, and most commonly reported as tenderness (15 [60%] of 25 participants [95% CI 39-79]) and pain (11 [44%] of 25 [24-65]) after intramuscular injection; and as tenderness (33 [66%] of 50 [51-79]), erythema (20 [40%] of 50 [26-55]), and pruritus (41 [82%] of 50 [69-91]) after vaccination by microneedle patch application. The geometric mean titres were similar at day 28 between the microneedle patch administered by a health-care worker versus the intramuscular route for the H1N1 strain (1197 [95% CI 855-1675] vs 997 [703-1415]; p=0·5), the H3N2 strain (287 [192-430] vs 223 [160-312]; p=0·4), and the B strain (126 [86-184] vs 94 [73-122]; p=0·06). Similar geometric mean titres were reported in participants who self-administered the microneedle patch (all p>0·05). The seroconversion percentages were significantly higher at day 28 after microneedle patch vaccination compared with placebo (all p<0·0001) and were similar to intramuscular injection (all p>0·01). Use of dissolvable microneedle patches for influenza vaccination was well tolerated and generated robust antibody responses. National Institutes of Health.

P061: Preventable adverse drug events in Canadian emergency departments

Introduction: Adverse drug events (ADEs), unintended and harmful events associated with medications, cause or contribute to 2 million emergency department (ED) visits in Canada each year. Our objective was to determine the proportion of preventable ADEs by event type, severity, drug and drug class, and describe associated factors. Methods: We reviewed the charts of ADE patients enrolled in 1 of 3 prospective studies conducted in 3 tertiary care and 1 urban community ED. In the parent studies, researchers enrolled patients by applying a systematic selection algorithm to minimize selection bias, and physicians and pharmacists evaluated patients prospectively to evaluate causal associations between the drug regimens and patient presentations. After completion of the prospective study, a research pharmacist and physician independently reviewed the charts of all ADE patients, abstracted data using an electronic form and applied 3 preventability algorithms. The main outcome was a probably or definitely preventable ADE defined as avoidable by adhering to best medical practice, appropriate monitoring, taking a history of prior ADEs, compliance with recommended therapy, and avoidance of errors. Reviewers discussed discordant ratings until reaching consensus. We used kappa scores to evaluate between rater agreement, and investigated risk factors for preventability using logistic regression. Sample size was based on enrolment into the parent studies. Results: We reviewed the charts of 670 patients diagnosed with 725 ADEs. We excluded 44 patients with incomplete assessments. The inter-rater agreement in categorizing ADEs as preventable was 0.51 (95%CI 0.42-0.59). We deemed 61% (95%CI 57-65%) of ADEs preventable. Of preventable events, 30% were due to non-adherence, 24% to adverse reactions, and 15% to an excessive dose, and 29% required hospital admission. Among preventable events, 8% were due to warfarin, 5% hydrochlorothiazide, 3% acetylsalicylic acid, and 3% insulin. On multivariate analysis, mental health diagnoses were associated with preventable ADEs (OR 2.1, 95%CI 1.3-3.3, p=0.002). Conclusion: In this large multi-centre cohort, preventable events made up the majority of ADEs, and utilized substantial hospital resources. Strategies to reduce ED visits due to ADEs should target improving adherence behavior, and developing interventions for patients with mental health diagnoses and on high-risk medications.

LO91: Repeat exposures to culprit drugs contribute to adverse drug events in emergency department patients

Introduction: Adverse drug events (ADEs), unintended and harmful events associated with medications, cause or contribute to 2 million annual emergency department (ED) visits in Canada. Australian data indicate that 27% of ADEs requiring admission are events caused by re-exposure to drugs that previously caused harm. Our objective was to estimate the frequency of repeat ADEs. Methods: We reviewed the charts of ADE patients who had been enrolled in 1 of 3 prospective studies conducted in 2 tertiary care and 1 urban community ED. In the parent studies, researchers enrolled patients by applying a systematic selection algorithm to minimize selection bias, and physicians and pharmacists evaluated patients prospectively to evaluate the causal association between the drug regimens and patient presentations. After completion of the parent studies, a research pharmacist and a physician independently reviewed the charts of ADE patients, abstracted data using electronic forms, and searched that hospital’s records for previously recorded ADEs. The main outcome was a repeat ADE, defined as a same or same-class drug re-exposure, or repeat inappropriate drug withdrawal, causing a same or similar presentation as a prior ADE. Sample size was based on enrolment into the parent studies. Results: We reviewed the charts of 614 ED patients diagnosed with 655 ADEs. Of these, 20% (133/665, 95%CI 17.0-23.0%) were repeat events. Most repeat ADEs were moderate (61%) or severe (32%) in nature, and 33% (95%CI 25.1-41.1%) required hospital admission. The most commonly implicated drugs were warfarin (10%), hydrochlorothiazide (4%) and insulin (4%), and the most commonly implicated drug classes were antithrombotics (17%), psychotropics (12%) and analgesics (9%). Repeat ADEs commonly required clinical monitoring (59%), additional medications to treat the ADE (50%) and follow-up lab testing (35%). Overall, 61% (95%CI 51.3-70.7%) of culprit drug re-exposures were deemed potentially or definitely inappropriate. Conclusion: Inappropriate re-exposures to previously harmful medications cause a substantial number of recurrent ADEs, and may represent an ideal target for prevention. We were unable to search for repeat ADEs in the records of other hospitals that our patients may have visited, and could not detect ADEs that were not documented in the medical record. As a result, we likely underestimated the frequency of repeat ADEs.

LO92: Factors contributing to the development of adverse drug events treated in emergency departments

Introduction: Adverse drug events (ADEs), unintended and harmful events associated with medications, commonly cause or contribute to emergency department (ED) presentations. Understanding provider, patient and system factors that contribute to their development may assist in developing effective preventative strategies. Our objective was to identify factors that contributed to the development of ADEs that caused ED presentations. Methods: We reviewed the charts of ADE patients enrolled in 1 of 3 prospective studies conducted in 3 tertiary care and 1 urban community ED. In the parent studies, researchers enrolled patients by applying a systematic selection algorithm to minimize selection bias, and physicians and pharmacists evaluated patients prospectively to evaluate the causal associations between the drug regimens and patient presentations. Subsequently, a research pharmacist and physician independently reviewed the charts of ADE patients from these cohorts, abstracting data using electronic forms. Reviewers recorded patient, provider and system factors that contributed to the development of ADEs. The main outcome was the presence of at least one contributing factor in the development of an ADE. We used descriptive statistics with appropriate measures of variance. The sample size was determined by enrolment into the primary studies. Results: We reviewed the charts of 670 patients diagnosed with 725 ADEs. We identified ≥1 contributing factors in 62% (95%CI 58-65%) of ADEs. Multiple contributing factors were present in 17% of ADEs (95%CI 13-20%). The most common contributing factors were inadequate patient counseling or instructions about medication use (15%), insufficient laboratory monitoring or follow-up of monitoring tests (12%), lack of staff education (7%), lack of provider adherence with recommended treatment guidelines (7%), and delayed or inadequate clinical reassessment after a medication change (6%). Provider errors in drug administration contributed to 0.3% of ADEs (95%CI 0.0-0.7). Conclusion: Contributing factors were identified for most ADEs. They were often related to inadequate counseling and follow-up, and were rarely the result of errors. Further research is required to understand how communication of medication instructions can be improved. Investments in technologies to reduce provider errors may not significantly reduce the numbers of ADE patients presenting to EDs.

LO51: Incidence of clinically relevant medication errors after implementation of an electronic medication reconciliation process

Introduction: Medication discrepancies are unintended differences between a patient’s outpatient and inpatient medication regimens, and occur in up to 60% of hospital admissions. Canadian emergency departments (EDs) have implemented medication reconciliation forms that are pre-populated with outpatient medication dispensing data in order to reduce medication discrepancies and resultant adverse drug events. However, these forms may introduce errors of commission by prompting prescribers to reorder discontinued or potentially harmful medications. Our objective was to evaluate the incidence of medication discrepancies and errors of commission after the implementation of pre-populated medication reconciliation forms. Methods: This chart review included admitted patients who were enrolled in a parent study in which a research pharmacist prospectively collected best-possible medication histories (BPMHs) in the ED using all available information sources. Following discharge, research assistants uninvolved with the parent study compared medication orders documented within 48 h of admission with the BPMH to identify medication discrepancies and errors of commission. Errors of commission were defined as inappropriate continuations of medications and reordering discontinued medications. An independent panel adjudicated the clinical significance of the errors. We used regression methods to identify factors associated with errors. The sample size was limited by enrolment into the parent study. Results: Of 151 patients, 71 (47%; 95%CI 39.2-54.9) were exposed to 112 medication errors. Of these errors, 75.9% (85/112; 95%CI 67.1-82.9) were discrepancies, of which 18.8% (16/85; 95%CI 12.0-28.4) were clinically significant. Errors of commission made up 24.1% (27/112; 95%CI 17.3-32.8) of all errors, of which 37.0% (10/27; 95%CI 18.8-55.2) were clinically significant. Taking 8 or more medications was associated with a 5-fold greater odds of experiencing a medication error after controlling for confounders (OR 5.00; 95%CI 2.45-10.17; p&amp;lt;0.001). Conclusion: Clinically significant medication discrepancies and errors of commission remain common despite the implementation of electronically pre-populated medication reconciliation forms. Prospective studies are needed to evaluate whether using pre-populated medication reconciliation forms increases the risk of introducing errors of commission.

Incidence of clinically relevant medication errors in the era of electronically prepopulated medication reconciliation forms: a retrospective chart review.

To reduce medication discrepancies (unintended differences between a patient's outpatient and inpatient medication regimens), Canadian institutions have implemented medication reconciliation forms that are prepopulated with outpatient medication dispensing data. These may prompt prescribers to reorder discontinued medications or continue newly contraindicated medications. Our objective was to evaluate the incidence of medication discrepancies and errors of commission after the implementation of such forms. This retrospective chart review included patients previously enrolled in an observational study in which a research pharmacist prospectively collected best-possible medication histories in the emergency department. Research assistants uninvolved with the parent study compared medication orders written in the first 48 hours after admission with the research pharmacist's best-possible medication history to identify medication discrepancies and errors of commission, defined as inappropriate medication continuations and reordering of previously stopped medications. An independent panel adjudicated the clinical significance of the errors. Of 151 patients, 71 (47.0% [95% confidence interval (CI) 39.2-54.9]) were exposed to 112 medication errors on admission. Of the 112 errors, 24 (21.4% [95% CI 14.9-29.9]) were clinically significant. Errors of commission accounted for 24.1% (27/112 [95% CI 17.3-32.8]) of all errors; 10 (37.0% [95% CI 18.8-55.2]) of the errors of commission were clinically significant. Medication errors were common after the implementation of electronically prepopulated medication reconciliation forms. Prospective research is required to examine the impact of prepopulated medication reconciliation forms and ensure they do not facilitate errors of commission.

Opportunities for pharmacists to optimise quality use of medicines in a Sri Lankan hospital: an observational, prospective, cohort study

AbstractBackgroundQuality use of medicines (QUM) has been identified as a priority in Sri Lanka.AimTo identify opportunities to optimise QUM, and evaluate medication appropriateness and medication information exchanged with patients and carers on discharge in a Sri Lankan tertiary care hospital.MethodsAn observational, prospective, cohort study of patients systematically sampled from two medical wards. A research pharmacist determined their pre‐admission medication regimen via interview at time of discharge. Issues of poor adherence and discrepancies between the pre‐ and post‐admission medication regimens were recorded. Drug‐related problems were categorised into opportunities to optimise drug therapy. The appropriateness of discharge medications was evaluated using a validated tool. The patient or carer was interviewed after discharge regarding the quality of medicine information exchanged in hospital.ResultsThe 578 recruited patients were taking 1756 medications prior to admission, and 657 (37.4%) of these medications were not continued during admission. Opportunities to optimise drug therapy were identified on 1496 occasions during admission (median, 2.0 opportunities/patient), 215 opportunities, (14.4%) were resolved spontaneously by the medical team prior to discharge. The median score for appropriateness of medications on discharge was 1.5 per patient (interquartile range, 0.0–3.5). Of 427 patients surveyed after discharge, 52% recalled being asked about their medications on admission to hospital, 75% about previous adverse medication reactions and 39% recalled being informed about changes to their medications on discharge.ConclusionSignificant opportunities exist for pharmacists to enhance quality use of medicines for patients in the current hospital‐based healthcare system in Sri Lanka.

Frequency and Impact of Pharmacist Interventions in Clinical Trial Patients With Diabetes

PurposeThe objective of this study was to describe the interventions and impact made by pharmacists during clinical trials. MethodsA specialty contract research organization that used clinical trial research pharmacists to communicate with patients to support clinical trial protocol adherence, retention, and health outcomes performed a retrospective, descriptive analysis of 12 clinical trials that involved 2 noninsulin glucose-lowering medications. Pharmacists called study participants at specific timepoints during the trials as per protocol. During each telephone call, the number and types of interventions were documented. Descriptive statistics (frequencies) were performed to determine the number and type of interventions by call and by patient across all noninsulin glucose-lowering medication drug A and drug B studies. FindingsOverall, 25,829 calls were made across all studies. Of these calls, 11,765 calls (45.5%) had at least one intervention that involved 3573 patients (92.3%). The most frequent interventions addressed adverse events (3774 [14.6%]), protocol violations for medication use (3341 [12.9%]), concurrent medications (1630 [5.9%]), and miscellaneous concerns (1269 [4.6%]). The greatest numbers of interventions were high-impact interventions (4772 [18.5%]) (eg, serious adverse events) that would seriously affect trial outcomes and patient adherence. ImplicationsPharmacists were able to identify, support, and address multiple types of interventions related to medication management during clinical trials, including those related to concurrent medication use, adverse events, and other medication-related issues. These pharmacist interventions can result in better patient outcomes and, ultimately, more reliable study results for review and approval by regulatory agencies.

Abstract OT3-07-04: A randomized study comparing MoistHer to topical lidocaine for female breast cancer survivors with dyspareunia

Abstract BACKGROUND: Problems related to sexual function are known to affect quality of life in female breast cancer survivors (BCS). A leading symptom of sexual dysfunction reported by BCS is dyspareunia, defined as moderate to severe penetrative pain with intercourse that results in reduced frequency of intercourse or abstinence. Dyspareunia in females is most commonly caused by vaginal dryness and primarily treated with estrogen therapy, a contraindication for many BCS. A recent trial found that estrogen-deficient BCS with dyspareunia who applied topical lidocaine to the vulvar vestibule (VV) prior to penetrative intercourse (PI) reported decreased pain during PI and improvement of sexual distress (Goetsch MF, JCO 2015). Identification of additional non-hormonal therapies to target the VV prior to PI may therefore provide treatment options for the improvement of sexual dysfunction in BCS with dyspareunia. TRIAL DESIGN: This is a double-blind, randomized trial to evaluate the benefits of applying natural lubricant MoistHer (MH) to the VV prior to PI in female BCS with dyspareunia. Subjects must be female ≥18 years BCS without active treatment (except for hormonotherapy), in a stable heterosexual partnership for ≥5 years, and report ≥ 3 months of consistent pain with PI. Patients with a history of pelvic pain, pelvic floor myalgia, vulvar dermatoses, or vaginismus will be excluded. Subjects will be randomized 1:1 to blinded home therapies of either MH or Topical Lidocaine (TL) for application to VV. MH is a commercially available vaginal moisturizer made of emu oil, tocopherol, safflower oil, and aloe extract and will be supplied by manufacturer Dromeo Inc. TL will be a 4% aqueous lidocaine hydrochloride solution prepared by research pharmacist (RP). Both MH and TL will be dispensed by RP in identical unmarked bottles. Subjects will agree to apply study liquid to VV and attempt PI at least twice per week for 4 weeks while maintaining a study diary to record pain scores. Outcomes will be measured via Sexual Function Questionnaire (SFQ), Female Sexual Distress Score-Revised (FSDS-R), and a rating of pain during PI on a scale of zero (no pain) to 10 (worst pain) via Numerical Rating Scale (NRS), to be completed by subjects at baseline, 2 weeks, and 4 weeks. AIMS: Primary endpoint is pain with PI, to be reported as a score on the NRS. Secondary endpoints are improved quality of sexual life and resumption of PI, to be measured by the SFQ and FSDS-R. STATS/TARGET ACCRUAL: A total of 50 patients will be recruited and randomized to receive either MH or TL at a 1:1 ratio (25 per group) using the Pocock-Simon dynamic allocation method. This sample size will achieve 94% power to detect at least 1.5 points NRS mean difference between treatments. NRS change will be compared between the two arms using a two-sample t-test (Pooled Standard error or Satterthwaite approximation as appropriate). Secondary outcomes include the SFQ and FSDS-R for which a longitudinal analysis of subscale scores will be conducted using a generalized linear mixed-effects model with fixed effects for treatment group and time. All statistical analyses will be conducted using SAS 9.3 [SAS Institute Inc., Cary, NC, USA]. Statistical significance will be defined as p &amp;lt; 0.05. Citation Format: Bendinger GM, Baptist S, Alvarez Tapias C, McGuire E, Rados K, Nixon D, Randolph K, McNight JE, Pabbathi H, Panicker R, Johnson AT, Geisler JP, Manahan KJ, Lammersfeld C, Avarez RH. A randomized study comparing MoistHer to topical lidocaine for female breast cancer survivors with dyspareunia [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-07-04.

The role of academic pharmacists in science and research

The role of academic pharmacists in science and research