Active Surveillance For Adverse Events Research Articles

Active surveillance of adverse events following immunization (AEFI): a prospective 3-year vaccine safety study.

Background:Vaccines used in national immunization programs are considered safe and effective but immunization safety has become as important as the efficacy of vaccination programs. The objective of the study was to detect adverse events following immunization (AEFIs) to all vaccines administered to a pediatric population in India.Methods:The prospective active vaccine safety surveillance study enrolled eligible children in the age group 0–5 years receiving vaccination from the immunization center at JSS Hospital, Mysuru. Study participants were monitored at the site for 30 min following vaccination and a telephonic survey was made after 8 days to identify all AEFIs. Causality assessment of the AEFIs were done using a new algorithm developed by the safety and vigilance department of the World Health Organization.Results:The incidence of reported AEFIs was 13.7%. The most frequently reported AEFI was fever (n = 3095, 93.2%) with an incidence of 109.7 per 1000 doses of vaccine administered, followed by persistent crying (n = 69, 2.4 per 1000 doses of vaccine) and diarrhea (n = 57, 2.0 per 1000 doses of vaccine). The majorly implicated vaccine for AEFIs was Pentavac® followed by BCG. Consistent causal association to immunization was observed in 93.4% of cases.Conclusions:A high incidence rate of AEFI was observed in our study population when compared with previous published studies. AEFI surveillance studies help to detect changes in the frequency of adverse events, which may be an alert to consider vaccine quality or identify a specific risk among the local population.

Short-term safety of 4CMenB vaccine during a mass meningococcal B vaccination campaign in Quebec, Canada

BackgroundTo address a high incidence of serogroup B invasive meningococcal disease (IMD-B) in the Saguenay–Lac-Saint-Jean region, Quebec, Canada, a mass vaccination campaign targeting nearly 60,000 individuals ≤20 years old was launched in May 2014. Because of the limited clinical experience with the four-component meningococcal B vaccine (4CMenB), active surveillance for adverse events following immunization (AEFI) was conducted. This paper reports 4CMenB AEFI surveillance findings. MethodsActive surveillance assessed AEFIs with acute onset within 7-days post-immunization, AEFI-associated absenteeism and medical consultations, impact of antipyretic prophylaxis and coadministration of other vaccines. ResultsBy July 17, 2015, 83% and 77% of the 59,098 individuals targeted by the campaign had received a first and a second dose of 4CMenB. The incidence of fever on days1-2 was highest in children <2 years old but only 0.6% reported a temperature ≥40◦C. Among children <10 years old, ≥2doses of acetaminophen prophylaxis significantly reduced fever incidence on days1-2 after dose1&2. Absenteeism or a medical consultation during the 7 days following vaccination was reported by 6.2% of vaccinees post-dose1 and 9.2% post-dose2 and was most often reported in association with fever/malaise (4.2%) or injection site reactions (3.6%). ConclusionLarge-scale population-based surveillance identified a 7-day reactogenicity profile consistent with earlier clinical trials with the 4CMenB vaccine but indicating frequent AEFI-associated absenteeism and medical consultations affecting the societal cost of this vaccine. We conclude acceptable vaccine safety and risk-benefit profile overall on the short term, particularly as an intervention to address a high regional incidence of IMD-B.

Participant-centred active surveillance of adverse events following immunisation: a narrative review.

The importance of active, participant-centred monitoring of adverse events following immunisation (AEFI) is increasingly recognised as a valuable adjunct to traditional passive AEFI surveillance. The databases OVID Medline and OVID Embase were searched to identify all published articles referring to AEFI. Only studies which sought participant response after vaccination were included. A total of 6060 articles published since the year 2000 were identified. After the application of screening inclusion and exclusion criteria, 25 articles describing 23 post-marketing AEFI systems were identified. Most countries had a single system: Ghana, Japan, China, Korea, Netherlands, Singapore, Brazil, Cambodia, Sri Lanka, Turkey and Cameroon except the USA (2), Canada (4) and Australia (6). Data were collected from participants with and without AEFI in all studies reviewed with denominator data enabling AEFI rate calculations. All studies considered either a single vaccine or specified vaccines or were time limited except one Australian system, which provides continuous automated participant-centred active surveillance of all vaccines. Post-marketing surveillance systems using solicited patient feedback are emerging as a novel AEFI monitoring tool. A number of exploratory systems utilising e-technology have been developed and their potential for scaling up and application in low and middle income countries deserves further investigation.

Active surveillance evaluation of anti-HPV vaccine adverse events in Umbria region

The study is a part of the "Active surveillance of adverse events following HPV vaccination" project conducted in order to actively register all common adverse events in girls 9-26 years after anti-HPV vaccination. It is a multicenter cohort study which included 12 Regions and 87 local health authorities, coordinated by the National Centre for Epidemiology, Surveillance and Health Promotion (CNESPS) ISS. We included all adolescents, 12 years old, actively contacted for HPV vaccination, as well as all women aged 9-26 years who recived, in the period under review, the same vaccination at the local health authorities in Spoleto. Out of 147 girls enrolled in the program, only 102 have reported the diary filled after the first vaccine dose, 62 and 88 respectively after the second and third dose. The filled diaries shown that adverse events, if any, have occurred almost exclusively during the first 5 days of vaccination, with a strong prevalence of local reactions (erythema, pain and swelling at the injection site) followed by headache and muscles pain. Even though the results show a high number of reported adverse events, mainly due to the detection method (active surveillance), they are mild or moderate in almost all the cases. This is in line with that seen in previous trials.

Active surveillance for adverse events among patients who underwent renal transplantation: A prospective observational study.

Aim:Renal transplantation is the treatment of choice for end-stage renal disease patients. Renal transplant recipients, however, have to be on lifelong therapy with immunosuppressants, which are associated with a number of adverse events (AEs). The safety profile of these immunosuppressants is not clear with respect to the Indian population. This study was conducted to find the frequency and pattern of all AEs experienced by Indian renal transplant recipients during the initial 3 months posttransplantation.Methods:Adults undergoing their first renal transplantation were enrolled in the study. All enrolled subjects were followed up for a maximum period of 3 months. All AEs were graded for severity and classified according to the Common Terminology Criteria for AEs criteria.Results:Ninety-eight renal transplant recipients enrolled in the study. There was a loss of follow-up of 7%. Five subjects died during the study. Subjects experienced on an average 9 AEs during the study. There was no difference in frequency of AEs between those on tacrolimus and cyclosporine. Most commonly observed AEs belonged to “Investigational” and “Metabolism and Nutrition” system organ classes. The most common AE was hypokalemia. New-onset diabetes after transplantation (NODAT) developed in 28% of subjects. There were 27 episodes of acute nephrotoxicity.Conclusion:The incidence of NODAT in the Indian population is substantially higher than that observed in the Western population. The incidence of nephrotoxicity may indicate higher sensitivity of the Indian population to calcineurin inhibitors.

Continuous active surveillance of adverse events following immunisation using SMS technology

IntroductionOn-going post-licensure surveillance of adverse events following immunisation (AEFI) is critical to detecting and responding to potentially serious adverse events in a timely manner. SmartVax is a vaccine safety monitoring tool that uses automated data extraction from existing practice management software and short message service (SMS) technology to follow-up vaccinees in real-time. We report on childhood vaccine safety surveillance using SmartVax at a medical practice in Perth, Western Australia. MethodsParents of all children under age five years who were vaccinated according to the Australian National Immunisation Schedule between November 2011 and June 2015 were sent an SMS three days post administration to enquire whether the child had experienced a suspected vaccine reaction. Affirmative replies triggered a follow-up SMS requesting details of the reaction(s) via a link to a survey that could be completed using a smartphone or the web. Rates of reported AEFI including fever, headache, fatigue, rash, vomiting, diarrhoea, rigours, seizures, and local reactions were calculated by vaccination time point. ResultsOverall, 239 (8.2%; 95% CI 7.2–9.2%) possible vaccine reactions were reported for 2897 vaccination visits over the 44 month time period. The proportion of children experiencing a possible AEFI, mostly local reactions, was significantly greater following administration of diphtheria–tetanus–pertussis–poliomyelitis vaccine at 4 years of age (77/441; 17.5%; 95% CI 13.9–21.0%) compared to the vaccinations given at 2–18 months (p<0.001). Across all time points, local reactions and fatigue were the most frequently reported AEFI. ConclusionAutomated SMS-based reporting can facilitate sustainable, real-time, monitoring of adverse reactions and contribute to early identification of potential vaccine safety issues.

Active Surveillance for Adverse Events After a Mass Vaccination Campaign With a Group A Meningococcal Conjugate Vaccine (PsA-TT) in Mali.

Background. The monovalent meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed for use in the “meningitis belt” of sub-Saharan Africa. Mali was 1 of 3 countries selected for early introduction. As this is a new vaccine, postlicensure surveillance is particularly important to identify and characterize possible safety issues.Methods. The national vaccination campaign was phased from September 2010 to November 2011. We conducted postlicensure safety surveillance for PsA-TT in 40 government clinics from southern Mali serving approximately 400 000 people 1–29 years of age. We conducted analyses with individual-level data and population-level data, and we calculated rates of adverse events using the conditional exact test, a modified vaccine cohort risk interval method, and a modified self-controlled case series method for each outcome of interest, including 18 prespecified adverse events and 18 syndromic categories.Results. An increased rate of clinic visits for fever within 3 days after vaccination was found using multiple methods for all age groups. Although other signals were found with some methods, complete assessment of all other prespecified outcomes and syndromic categories did not reveal that PsA-TT was consistently associated with any other health problem.Conclusions. No new safety concerns were identified in this study. These results are consistent with prelicensure data and other studies indicating that PsA-TT is safe. The approach presented could serve as a model for future active postlicensure vaccine safety monitoring associated with large-scale immunization campaigns in low-income countries.

Comparison of text-messaging to voice telephone interviews for active surveillance of adverse events following immunisation

ObjectivesIn 2013, the Follow-up and Active Surveillance of Trivalent Influenza Vaccine in Mums (FASTMum) program began using short message service (SMS) to collect adverse event information in pregnant women who recently received trivalent influenza vaccine (TIV). This study was designed to compare data collected via SMS and telephone for the purposes of monitoring vaccine safety. MethodsA number of 344 women who received TIV were randomly assigned to a telephone interview group. They were telephoned seven days post-vaccination and administered a standard survey soliciting any adverse events following immunisation (AEFI) they experienced. They were matched by brand of vaccine, age group, and residence to 344 women who were sent a SMS seven days post-vaccination. The SMS solicited similar information. AEFI reported by SMS and telephone interview were compared by calculating risk ratios. ResultsResponse rate was higher to SMS compared to telephone interview (90.1% vs. 63.9%). Women who were surveyed by SMS were significantly less likely to report an AEFI compared to women who were surveyed by telephone (RR: 0.41; 95% CI: 0.29–0.59). The greatest discrepancies between SMS and telephone interview were for self-reported injection site reactions (3.1% vs. 16.8%) and unsolicited (or “other”) events (11.4% vs. 4.1%). Data collected by SMS was significantly timelier. ConclusionsData collection by SMS results in significantly improved response rates and timeliness of vaccine safety data. Systems which incorporate SMS could be used to more rapidly detect safety signals and promote more rapid public health response to vaccine quality issues.

Active Surveillance for Adverse Events Within 90 Days: The Standard for Reporting Surgical Outcomes After Pancreatectomy.

The rate of adverse events after pancreatectomy is widely reported as a measure of surgical quality. However, morbidity data are routinely acquired retrospectively and often are reported at 30 days. The authors hypothesized that morbidity after pancreatectomy is therefore underreported. They sought to compare rates of adverse events calculated at multiple time points after pancreatectomy. The authors instituted an active surveillance system to detect, categorize, and grade the severity of all adverse events after pancreatectomy, using the modified Accordion system and International Study Group of Pancreatic Surgery definitions. All patients and clinical events were monitored directly for at least 90 days after surgery. Of 315 consecutively monitored patients, 239 (76 %) experienced 500 unique adverse events. The absolute number of unique adverse events increased by 32 % between index discharge and 90 days and by 10 % between 30 and 90 days. The number of severe adverse events increased by 96 % between discharge and 90 days and by 29 % between 30 and 90 days. In this study, 16 % of the patients experienced at least one severe adverse event within the index hospitalization, 24 % within 30 postoperative days, and 29 % within 90 days. Among the 80 readmissions that occurred within 90 days, 28 (35 %) occurred later than 30 days after pancreatectomy. Approximately one-third of severe adverse events and readmissions are reported more than 30 days after surgery. All adverse events that occur within 90 days of surgery must be identified and reported for accurate characterization of the morbidity associated with pancreatectomy.

Strategy support for the Post‐Market Monitoring (PMM) of GM plants: Review of existing PMM strategies developed for the safety assessment of human and animal health

Strategy support for the Post‐Market Monitoring (PMM) of GM plants: Review of existing PMM strategies developed for the safety assessment of human and animal health

Routine surveillance of adverse events following immunization as an important tool to monitor vaccine safety

Post licensure surveillance of adverse events following immunization (AEFI) is a fundamental activity to improve safety and maintain public confidence in vaccines. Since 2011, the Liguria Region has been involved in the inter-regional project of post-marketing surveillance of AEFI, coordinated by the Italian Medicine Agency and the Veneto region. The main objectives of the project are: (1) to coordinate the surveillance activities in the 8 Italian Regions included in the project; (2) to encourage the signal of AEFI by healthcare workers and patients; (3) to organize education activities addressed to health care workers, and, finally; (4) to establish vaccination counseling services in each Region. In particular, the Ligurian multidisciplinary team, composed by physicians expert in the field of vaccination and pharmacists, is involved in the causality assessment between vaccines and all adverse events signaled within the Liguria Region and in the analysis of all adverse events signaled in Italy as possibly related to influenza vaccines. During 2013, the team has organized 4 courses, addressed to healthcare personnel of vaccination outpatient clinics, focused on European and Italian legislation on pharmaco-vigilance and vaccine-vigilance and aimed at promoting signal of AEFI. Since October 2013, the Liguria Region has been participating to the inter-regional project of active surveillance of adverse events aimed at promoting the signal of AEFI by parents of vaccinated infants. After two years of implementation of the project both the number of reported AEFI and the reporting rate per 100 000 administered doses of vaccine increased. The activities need to be consolidated in the next years in order to guarantee high standard of vaccine safety, maintain the confidence in current immunization programs and reach optimal vaccination coverage rate.

Active surveillance of adverse events following childhood immunization in Singapore

IntroductionIn Singapore, reporting of adverse events following immunization (AEFI) was historically passive. In 2009, Health Sciences Authority collaborated with KK Women's and Children's Hospital to perform active surveillance for AEFI. We report the methodology and initial findings of this surveillance following childhood vaccines. MethodsFrom April 2010 to March 2012, we screened all paediatric admissions for possible relationships to vaccination, excluding elective admissions, and performed causality assessment for each case using standardized definitions for certain, probable, possible and unlikely. Baseline demographics, data on implicated vaccines and clinical details including severity and outcomes were collected. Total hospital admissions were used to calculate rates of AEFI. ResultsWe screened 45,571 (80%) of 56,526 admissions, and evaluated 1988 (4.4%) children. Median age at presentation was 3.1 months, while median interval from vaccination to symptom onset was 6 days. There were 311 (15.6%) children with AEFI that were considered possibly, probably or certainly associated with vaccines. However, 98.8% recovered without any long-term sequelae. The hospital-based active surveillance of AEFI enabled the detection of a 5-fold increase (95% CI 1.2–33.1) in BCG-associated regional lymphadenitis in April 2010, which triggered follow-up safety analysis to guide public health advice. ConclusionsHospital-based active surveillance can enhance signal detection and follow-up investigations of AEFI. Subsequently, public health bodies are better equipped to maintain public confidence in vaccination programmes and physicians are able to provide relevant advice to parents. It also allows for a better understanding of risk-benefit ratios of specific vaccines and aids the generation of public health vaccination policy.

Guillain‐Barré syndrome following pandemic (H1N1) 2009 influenza A immunisation in Victoria: a self‐controlled case series

To determine the relative incidence (RI) of Guillain-Barré syndrome (GBS) in a single Australian state following pandemic (H1N1) 2009 influenza A immunisation (monovalent vaccine or seasonal trivalent influenza vaccine [TIV]) in 2009-2010. Active GBS surveillance (cases assessed by two neurologists according to the Brighton criteria) from 30 September 2009 to 30 September 2010, conducted at 10 hospitals in Victoria, Australia. The RI of GBS in the risk window of 0-42 days after vaccination. Sixty-six potential GBS cases were identified, with complete data on 50 confirmed cases. The Victorian annual incidence of GBS was 1.7 per 100 000 population. Three cases had received monovalent vaccine and one case had received seasonal TIV within 42 days of symptom onset. The RI of GBS following monovalent vaccination was 3.4 (95% CI, 0.8-15.0). For TIV, there was one case in the risk period (RI, 0.69; 95% CI, 0.08-5.64). This is the first published study reviewing GBS after a trivalent and/or monovalent influenza vaccine containing the pandemic (H1N1) 2009 strain, with only a small proportion of GBS cases occurring after influenza immunisation. H1N1-containing vaccines were not statistically associated with GBS, but this study could not exclude smaller increases in the RI. Active surveillance of adverse events following immunisation is required to maintain public and health care professional confidence in mass vaccine implementation programs.

Study of natural health product adverse reactions (SONAR): active surveillance of adverse events following concurrent natural health product and prescription drug use in community pharmacies.

BackgroundMany consumers use natural health products (NHPs) concurrently with prescription medications. As NHP-related harms are under-reported through passive surveillance, the safety of concurrent NHP-drug use remains unknown. To conduct active surveillance in participating community pharmacies to identify adverse events related to concurrent NHP-prescription drug use.Methodology/Principal FindingsParticipating pharmacists asked individuals collecting prescription medications about (i) concurrent NHP/drug use in the previous three months and (ii) experiences of adverse events. If an adverse event was identified and if the patient provided written consent, a research pharmacist conducted a guided telephone interview to gather additional information after obtaining additional verbal consent and documenting so within the interview form. Over a total of 112 pharmacy weeks, 2615 patients were screened, of which 1037 (39.7%; 95% CI: 37.8% to 41.5%) reported concurrent NHP and prescription medication use. A total of 77 patients reported a possible AE (2.94%; 95% CI: 2.4% to 3.7%), which represents 7.4% of those using NHPs and prescription medications concurrently (95%CI: 6.0% to 9.2%). Of 15 patients available for an interview, 4 (26.7%: 95% CI: 4.3% to 49.0%) reported an AE that was determined to be “probably” due to NHP use.Conclusions/SignificanceActive surveillance markedly improves identification and reporting of adverse events associated with concurrent NHP-drug use. Although not without challenges, active surveillance is feasible and can generate adverse event data of sufficient quality to allow for meaningful adjudication to assess potential harms.

Safety and pharmacokinetics of a human monoclonal antibody to rabies virus: A randomized, dose-escalation phase 1 study in adults

BackgroundRabies is an essentially fatal disease that is preventable with the timely administration of post-exposure prophylaxis (PEP). The high cost of PEP, which includes vaccine and hyperimmune globulin, is an impediment to the goal of preventing rabies in the developing world. Recently a recombinant human IgG1 anti-rabies monoclonal antibody (SII RMab) has been developed in India to replace serum-derived rabies immunoglobulin. The present study was conducted to demonstrate the safety of SII RMab and to determine the dose resulting in neutralizing serum antibody titers comparable to human rabies immunoglobulin (HRIG) when administered in conjunction with rabies vaccine in a simulated PEP regimen. MethodsThis randomized, open label, dose-escalation phase 1 study was conducted in healthy adults at a large tertiary care, referral, public hospital in India. Safety was assessed by active surveillance for adverse events along with standard laboratory evaluations and measurement of anti-drug antibodies (ADA). Anti-rabies antibody levels were measured by rapid fluorescent focus inhibition test (RFFIT) and ELISA. The study duration was 365 days. FindingsSII RMab was well tolerated with similar frequency of local injection site reactions to HRIG. The geometric mean concentrations of rabies neutralizing antibody in the vaccine plus SII RMab 10IU/kg cohort were comparable to the vaccine plus HRIG 20IU/kg cohort throughout the 365-day study period; day 14 geometric mean concentrations 23.4IU/ml (95% CI 14.3, 38.2) vs. 15.3IU/ml (95% CI 7.72, 30.3; p=NS), respectively. Future post-exposure prophylaxis studies of SII RMab at a dose of 10IU/kg in conjunction with vaccine are planned.

PS1-11: Feasibility of Prospective Surveillance for Adverse Drug Events - Lessons Learned from a 12-Month Pilot Study

Background/Aims When new medications are introduced, safety data are often sparse. Health plan data may be useful for active surveillance for adverse events. We conducted a 12-month pilot study to demonstrate the feasibility of prospective active surveillance using data from several large health insurers. This presentation will summarize logistical challenges and lessons learned.

Active Surveillance of Adverse Events Following Immunization against Pandemic Influenza A (H1N1) in Korea

Surveillance of vaccine safety is one of the public health interventions used to investigate the causal relationship between vaccines and adverse events. Using active surveillance data, we aimed to compile a detailed summary describing the safety of the pandemic influenza A (H1N1) vaccine. Computer-assisted telephone interview was used to investigate adverse events for 9,000 subjects who had received non-adjuvanted vaccines between November 2009 and January 2010, and for 19,000 adults who received adjuvanted vaccines from January through March 2010. The participants were interviewed to obtain information about local and systemic adverse events. Among subjects who received the non-adjuvanted vaccine, 5.5% (n=492) reported adverse events after vaccination, while 6.7% of those who received the adjuvanted vaccine reported adverse events. In the group receiving the adjuvanted vaccine, the highest reported rate of adverse events was among persons aged 19-49 years (9.1%, 577/6,329), followed by persons aged 50-64 years (7.2%, 485/6,718), and elderly persons aged 65 years and over (3.4%, 204/5,953). The implementation of this active surveillance study demonstrated the safety of both the adjuvanted and non-adjuvanted H1N1 vaccines.

Active Surveillance for Adverse Events: The Experience of the Vaccine Safety Datalink Project

To describe the Vaccine Safety Datalink (VSD) project's experience with population-based, active surveillance for vaccine safety and draw lessons that may be useful for similar efforts. The VSD comprises a population of 9.2 million people annually in 8 geographically diverse US health care organizations. Data on vaccinations and diagnoses are updated and extracted weekly. The safety of 5 vaccines was monitored, each with 5 to 7 prespecified outcomes. With sequential analytic methods, the number of cases of each outcome was compared with the number of cases observed in a comparison group or the number expected on the basis of background rates. If the test statistic exceeded a threshold, it was a signal of a possible vaccine-safety problem. Signals were investigated by using temporal scan statistics and analyses such as logistic regression. Ten signals appeared over 3 years of surveillance: 1 signal was reported to external stakeholders and ultimately led to a change in national vaccination policy, and 9 signals were found to be spurious after rigorous internal investigation. Causes of spurious signals included imprecision in estimated background rates, changes in true incidence or coding over time, other confounding, inappropriate comparison groups, miscoding of outcomes in electronic medical records, and chance. In the absence of signals, estimates of adverse-event rates, relative risks, and attributable risks from up-to-date VSD data have provided rapid assessment of vaccine safety to policy-makers when concerns about a specific vaccine have arisen elsewhere. Care with data quality, outcome definitions, comparison groups, and length of surveillance are required to enable detection of true safety problems while minimizing false signals. Some causes of false signals in the VSD system were preventable and have been corrected, whereas others will be unavoidable in any active surveillance system. Temporal scan statistics, analyses to control for confounding, and chart review are indispensable tools in signal investigation. The VSD's experience may inform new systems for active safety surveillance.

An assessment of the safety of adolescent and adult tetanus–diphtheria–acellular pertussis (Tdap) vaccine, using active surveillance for adverse events in the Vaccine Safety Datalink

Using a new sequential analytic method, the safety of tetanus–diphtheria–acellular pertussis (Tdap) vaccine was monitored weekly among subjects aged 10–64 years during 2005–2008. Encephalopathy–encephalitis–meningitis, paralytic syndromes, seizures, cranial nerve disorders, and Guillain-Barré syndrome were selected as outcomes based on previous reports and biologic plausibility. The risk following Tdap was not significantly higher than the risk after Td. Statistical power was sufficient to detect a relative risk of 4–5 for Guillain-Barré syndrome and 1.5–2 for the other outcomes. This study provides reassurance that Tdap is similar in safety to Td regarding the outcomes studied and supports the viability of sequential analysis for post-licensure vaccine safety monitoring.

Systematic review and meta‐analysis of clinically relevant adverse events from HMG CoA reductase inhibitor trials worldwide from 1982 to present

Our objective was to determine the association of clinically relevant adverse events from a systematic review and meta-analysis of statin randomized controlled trials (RCT). We performed the meta-analysis in the manner of a Cochrane Collaboration systematic review. Outcomes were discontinuances of therapy or muscle-related symptoms due to adverse events. We searched for articles from 1982 through June 2006 in MEDLINE and other databases. The main inclusion criteria were double blind, placebo controlled RCTs with a monotherapy intervention of any marketed statin and active surveillance of adverse events. We excluded studies of drug interactions, organ transplants, or exercise, or those not meeting all of the study quality criteria. The primary analysis was a statin formulation stratified fixed-effect model using Peto odds-ratios (POR). Secondary analyses explored the stability of the primary results. Over 86,000 study participants from 119 studies were included. Available statins were associated with a lower POR of discontinuance (overall: 0.88 [0.84, 0.93], largest effect with pravastatin: 0.79 [0.74, 0.84]), an elevated POR of rhabdomyolysis (1.59 [0.54, 4.70]) and myositis (2.56 [1.12, 5.85]), and null odds of myalgia (1.09 [0.97, 1.23]). Cerivastatin by comparison demonstrated larger PORs for discontinuances and muscle-related adverse events. Secondary analyses demonstrated the stability of the results. Overall, discontinuation of statin therapy due to adverse events was no worse than placebo. The risks of muscle-related adverse events were in general agreement with the known risks of statins.