How does a drug with a limited safety and efficacy record become an international blockbuster? In June 2006 the FDA approved and recommended a new vaccine directed against 4 types of sexually transmitted human papillomavirus, associated with 70% of cervical cancer cases and 90% of genital wart cases. Branded as a "cervical cancer vaccine" Gardasil has been met with as much fanfare as controversy, and retains blockbuster status in Merck's portfolio. Sold as a cancer risk-reduction method, Gardasil carries its own risks, with startlingly low efficacy and elevated likelihood of serious adverse events (side effects). Through the lens of risk, this dissertation examines Gardasil's popularity in the face of evidence that it is neither as safe nor as effective as advertised. Through three distinct research projects, I identify (a) five sociological factors responsible for Gardasil's success on the heels of Vioxx, one of the biggest drug scandals in history; (b) how amongst healthy vaccinated girls, cervical cancer is experienced as a "risk object," yet when a young woman experiences a serious adverse event that "object of risk" and her "experience of risk" shift toward Gardasil; and (c) that Gardasil is so trusted among young women, that warnings about potential side effects from others made some girls more likely to get vaccinated and have a positive opinion on the vaccine, suggesting that Gardasil benefits from a broader cultural assumption that vaccines are inherently safe and effective. Physicians and pharmaceutical marketing also play an important role. Gardasil is a risk-reduction drug and vaccine purported to treat risk while it simultaneously creates new risk for further health problems in some consumers. This dissertation contributes to sociological literatures on pharmaceuticalization, pharmaceutical pseudoscience, the social construction of risk, research on regulatory agencies, and the sociology of medicine more broadly.

Previous research has established a consensus that in-hospital adverse events are ubiquitous, cause significant harm to patients, and have important financial consequences. However, information on the extent, consequences and costs of adverse events in Canada is limited. For example, there is, as yet, no published study that has investigated the costs of adverse events in a Canadian context. This dissertation aims to redress this situation by providing Ontario-based estimates of the impact of eleven nursing sensitive adverse events on cost, death, readmission, and ambulatory care use within 90 days after hospitalization. This dissertation also aims to contribute more broadly to the patient safety literature by quantifying the impact of diagnostic coding error in administrative data on estimates of the excess costs attributable to adverse events. Given the increasing importance of these estimates in Canada and elsewhere for hospital payment policy and for assessments of the business case for patient safety, this is an important gap in the literature. Each of the adverse events was associated with positive excess costs, ranging from $29,501 (metabolic derangement) to $66,412 (pressure ulcers). Extrapolation from the study hospitals yielded a provincial estimate of $481 million in annual excess costs attributable to the adverse events, which represents 2.8 percent of Ontario’s total hospital expenditures. Several of the adverse events were also associated with significant excess rates of death, readmission, and ambulatory care use. These results suggest that there are economic as well as ethical reasons to improve patient safety in Ontario hospitals. Estimates of adverse event costs were highly sensitive to coding error. The excess cost of adverse events is likely to be significantly underestimated if the error is ignored. This finding, coupled with the observation that the likelihood of error is ignored in most studies, suggests that previous assessments of the business case for patient safety may have been biased against the cost effectiveness of patient safety improvements. Furthermore, the observed extent of institutional level variation in adverse event coding indicates that administrative data are an inadequate basis for adverse event payment policies or for public reporting of adverse event rates.

Did governments in different countries regulate common concerns about patient safety differently? If so how and why did they do this? This thesis undertakes a historical comparison of the regulation of patient safety in Britain and Canada between 1980 and 2005. These jurisdictions began the period with very similar regulatory frameworks, but by 2005 there were distinct differences in each jurisdiction‘s regulatory response to patient safety. Britain was very actively regulating all aspects of service provision within its health system in the name of patient safety, whereas Canada‘s regulatory direction showed adherence to the 1980s model with only scattered incremental developments. This thesis assesses the broader sociopolitical context and the structure of the health systems in each jurisdiction and concludes there are differences in the logics of these systems that established a foundation for future regulatory divergence. It is argued that between 1980 and 2005 there were two factors that influenced regulatory directionality in each jurisdiction: changing political norms associated with the development of neoliberalism and the New Public Management; and events or scandals associated with the provision of health services. The differing levels of penetration of both the changing political norms into governance cultures and of scandals into the public and political consciousness are critical to explaining regulatory differences between jurisdictions. The thesis concludes that what and how governments chose to regulate is a function of the perceived need for action and the dominant social and political norms within that society. Context is everything in the formulation of regulatory approaches to address pressing social problems.

Research into adverse events in home care is at a very early stage worldwide. Adverse event research in other health care sectors has demonstrated that patients can and do suffer harm, much of which is preventable, during the receipt of health care services. A stratified, random sample of patients who had received home care nursing service and were discharged in 2004/05 from three Ontario home care programs was studied to develop basic exploratory and descriptive evidence to advance the understanding of AEs in home care. The outcome is an estimate of the incidence of adverse events among patients, description of adverse event types and factors associated with adverse events, and the development of models predictive of home care patients with higher and lower potential for adverse events, and of the location of patients with adverse events. Positive critical indicators were identified in 66.5% of 430 cases. Sixty-one adverse events were identified in 55 (19.2%) of these 286 cases. When adjusted for sampling methodology, the adverse event rate was 13.2 per 100 patients (95%, CI 10.4% - 16.6%, SE 1.6%). Thirty-three percent of the adverse events were rated as having more than a 50% probability of preventability; 1.4% of all patients experienced an adverse event related death. Eight of the 45 factors significantly associated with adverse events formed a single factor model predictive of adverse events. Six two-factor interactions and the absence of one factor were also predictive of the occurrence of adverse events. Five of the 12 critical indicators significantly related to adverse events, as well as 7 critical indicator combinations formed models that reliably located about two-thirds of patients who had, and almost all patients who had not, experienced an adverse event. This study suggests that a significant number of home care patients experience adverse events, two-thirds of which are preventable. Use of adverse event sensitive factors as a screening tool for patients that may benefit from enhanced case management and clinical vigilance, and those unlikely to be placed at increased adverse event risk by maintaining current levels of vigilance, presents an opportunity to improve patient safety. Retrospective critical indicator models identifying home care patients who have experienced an adverse event can be used to estimate adverse event incidence rates and changes in rates over time.

Research into adverse events in home care is at a very early stage worldwide. Adverse event research in other health care sectors has demonstrated that patients can and do suffer harm, much of which is preventable, during the receipt of health care services. A stratified, random sample of patients who had received home care nursing service and were discharged in 2004/05 from three Ontario home care programs was studied to develop basic exploratory and descriptive evidence to advance the understanding of AEs in home care. The outcome is an estimate of the incidence of adverse events among patients, description of adverse event types and factors associated with adverse events, and the development of models predictive of home care patients with higher and lower potential for adverse events, and of the location of patients with adverse events. Positive critical indicators were identified in 66.5% of 430 cases. Sixty-one adverse events were identified in 55 (19.2%) of these 286 cases. When adjusted for sampling methodology, the adverse event rate was 13.2 per 100 patients (95%, CI 10.4% - 16.6%, SE 1.6%). Thirty-three percent of the adverse events were rated as having more than a 50% probability of preventability; 1.4% of all patients experienced an adverse event related death. Eight of the 45 factors significantly associated with adverse events formed a single factor model predictive of adverse events. Six two-factor interactions and the absence of one factor were also predictive of the occurrence of adverse events. Five of the 12 critical indicators significantly related to adverse events, as well as 7 critical indicator combinations formed models that reliably located about two-thirds of patients who had, and almost all patients who had not, experienced an adverse event. This study suggests that a significant number of home care patients experience adverse events, two-thirds of which are preventable. Use of adverse event sensitive factors as a screening tool for patients that may benefit from enhanced case management and clinical vigilance, and those unlikely to be placed at increased adverse event risk by maintaining current levels of vigilance, presents an opportunity to improve patient safety. Retrospective critical indicator models identifying home care patients who have experienced an adverse event can be used to estimate adverse event incidence rates and changes in rates over time.

Previous research has established a consensus that in-hospital adverse events are ubiquitous, cause significant harm to patients, and have important financial consequences. However, information on the extent, consequences and costs of adverse events in Canada is limited. For example, there is, as yet, no published study that has investigated the costs of adverse events in a Canadian context. This dissertation aims to redress this situation by providing Ontario-based estimates of the impact of eleven nursing sensitive adverse events on cost, death, readmission, and ambulatory care use within 90 days after hospitalization. This dissertation also aims to contribute more broadly to the patient safety literature by quantifying the impact of diagnostic coding error in administrative data on estimates of the excess costs attributable to adverse events. Given the increasing importance of these estimates in Canada and elsewhere for hospital payment policy and for assessments of the business case for patient safety, this is an important gap in the literature. Each of the adverse events was associated with positive excess costs, ranging from $29,501 (metabolic derangement) to $66,412 (pressure ulcers). Extrapolation from the study hospitals yielded a provincial estimate of $481 million in annual excess costs attributable to the adverse events, which represents 2.8 percent of Ontario’s total hospital expenditures. Several of the adverse events were also associated with significant excess rates of death, readmission, and ambulatory care use. These results suggest that there are economic as well as ethical reasons to improve patient safety in Ontario hospitals. Estimates of adverse event costs were highly sensitive to coding error. The excess cost of adverse events is likely to be significantly underestimated if the error is ignored. This finding, coupled with the observation that the likelihood of error is ignored in most studies, suggests that previous assessments of the business case for patient safety may have been biased against the cost effectiveness of patient safety improvements. Furthermore, the observed extent of institutional level variation in adverse event coding indicates that administrative data are an inadequate basis for adverse event payment policies or for public reporting of adverse event rates.

BACKGROUND: Transport of patients is sometimes necessary and unavoidable. However, there are many risks related to it. For this reason, safety of intra-hospital transport has been thoroughly studied in critical care patients; however there is no literature on adverse events during transport of trauma patients. Due to the acute nature of injury, trauma patients are fundamentally different than other populations of patients and require special consideration during transport. Lack of data makes initiating new protocols for transport conditions difficult. METHODS/RESULTS: Data from all activated trauma response patients who required transport to and from the CT scanner from the period of January 01, 2010 to December 31st, 2013 (total of 1103 patients) were collected. From these patients, 17 adverse events were identified (2.0% excluding missing documentation). Vomiting was the most common adverse event followed by peripheral IV line dislodgment. There were no cardiac arrests or deaths resulting from transport related events. CONCLUSION: Defining adverse events is a key part of evaluating safety during transport. Fluctuations in vital signs and other objective measures may reflect patient disease rather than transport. Our study provides clear definitions of what an adverse event is using outcomes and objectively identifies measures necessary for safe transport as well as areas of improvement.

abstract: For more than twenty years, clinical researchers have been publishing data regarding incidence and risk of adverse events (AEs) incurred during hospitalizations. Hospitals have standard operating policies and procedures (SOPP) to protect patients from AE. The AE specifics (rates, SOPP failures, timing and risk factors) during heart failure (HF) hospitalizations are unknown. There were 1,722 patients discharged with a primary diagnosis of HF from an academic hospital between January 2005 and December 2007. Three hundred eighty-one patients experienced 566 AEs, classified into four categories: medication (43.9%), infection (18.9%), patient care (26.3%), or procedural (10.9%). Three distinct analyses were performed: 1) patient's perspective of SOPP reliability including cumulative distribution and hazard functions of time to AEs; 2) Cox proportional hazards model to determine independent patient-specific risk factors for AEs; and 3) hospital administration's perspective of SOPP reliability through three years of the study including cumulative distribution and hazard functions of time between AEs and moving range statistical process control (SPC) charts for days between failures of each type. This is the first study, to our knowledge, to consider reliability of SOPP from both the patient's and hospital administration's perspective. AE rates in hospitalized patients are similar to other recently published reports and did not improve during the study period. Operations research methodologies will be necessary to improve reliability of care delivered to hospitalized patients. / Dissertation/Thesis / M.S. Industrial Engineering 2012

Bakgrund: Läkemedel är den vanligaste behandlingsformen inom sjukvården och samtidigt det är det bästa och mest effektiva alternativet, så är användningen av läkemedel förenat med risker och bieffekter. Dessa bieffekter är en av de ledande anledningarna till dödsfall i de flesta länder. Upp till 60 % av läkemedelsrelaterade problem skulle kunna undvikas. Det kan vara ett fel som kommer att skada, eller har potential att skada patienten, även kallad undvikbar läkemedelsavvikelse, som kan förekomma i läkemedelskedjan. I SVerige avlider 3150 personer per år av sådana skador. Syfte: Syftet med studien är att beskriva de undvikbara läkemedelsavvikelser som har rapporterats inom Synergi i Landstinget i Östergötland under 2011. Metod: Genomgång av landstinget avvikelserapporteringssystem Synergi med rapporter relaterade till läkemedel. Utifrån beskrivningen i fritexten bedömdes det som det handlade om en undvikbar läkemedelsavvikelse. Resultat: Under 2011 inkom 2750 rapporter varav 2320 klassades som undvikbara läkemedelsavvikelser och 6,7 % (n=155) av dessa ledde till skador. En patient avled till följd av en undvikbar läkemedelsavvikelse. Den vanligaste typen av fel var brist i rutin (n=1255) och vanligaste konsekvensen var uteblivna doser (n=604). Warfarin var det läkemedel som förekom i flest rapporter (n=140), medan uteblivna/för låga doser av heparin ledde till flest allvarliga skador (n=3). Slutenvården stod för 52 % (n=1211) av alla rapporter och även 80 % (n=125) av skadorna. Slutsats: Bristande rutiner kan vara en vanlig orsak till läkemedelsavvikelser. Därför behöver den svenska sjukvården satsa på att förbättra och förenkla sina rutiner, både mellan avdelningar och enskilt för att förbättra patientsäkerheten. Den har kommit en bit på väg, men behöver tydligare riktlinjer och mer utbildning och information till både avdelningar och de enskilda personer som arbetar inom sjukvården. / Background: Drugs are the most common way to treat illnesses in healthcare and the best and most efficient alternative. At the same time you must keep i mind that the use of drugs is always associated with risks and side effects. These side effects or adverse drug reactions are among the leading causes of death in many countries. At least 60 % of adverse drug reactions are preventable. A preventable drug reation is called a medication error. A medication error occurs when a failure in the treatment leads to harm to the patient, or has the potential to lead to harm to the patient. The treatment process is a chain of several events, from the diagnosis of an illness and the choice of drugs, to monitoring the administration. There are many steps from start to the end that all have the potential to lead to mistakes. Medication errors can lead to great costs for healthcare, poor quality of life for the patient or even death. In Sweden it is estimated that 3150 patients die annually caused by medication errors. Purpose: The purpose of this study was to describe medication errors in Landstinget i Östergötland (the County Council of Östergötland) in 2011. Method: Search was done through the error report system, Synergi, with medication error as a priority. From the description in the primary text judge if the report described a medication error. Results: During 2011 2750 reports were submitted to Synergi, and 2320 of these were identified as medication errors. 6,7 % (n=155) of these medication errors had caused harm to the patient, one of them died due to medication error. The most common type of failure was some sort lack of routine (n=1255) and it usually lead to errors of omission; whern a dose that should have been given was not (n=604). Warfarin, an anticoagulantia, was the most frequent drug in the reports (n=140), while a low dose/missed dose of heparin, another anticoagulantia, lead to harm that was classified as serious, to the patients (n=3). MOre than halfr of the reports were fro inpatient care, 52 % (n=1211) and also 80 % (n=125) of medication errors that caused harm to the patients. Conclusion: Lack of routine can be a major cause of medication errors and therefore Swedish healthcare needs to improve routines and even simplify them for easier and faster access for the staff. The cooperation between members of the staff in hospitals, health centers and community home care sholud be better to improve the safety of patients. The healthcare needs more guidance and education to overcome the lack of routines and even more resources for a labor intensive activity where the need for healthcare is increasing

Objectives: This thesis included 6 manuscripts which focused on the analysis of adverse events following immunization (AEFIs), including general health services utilization (emergency room (ER) visits and hospital admissions) and specific diagnoses (e.g. febrile convulsions). The main objectives of this research were: 1) To demonstrate the utility of the self-controlled case series (SCCS) design coupled with health administrative data for studying the safety of vaccines; 2) Introducing an innovative approach using relative incidence ratios (RIRs) within an SCCS analysis to identify risk factors for AEFIs and to overcome the healthy vaccinee bias; and 3) To demonstrate how SCCS and RIR analyses of health services outcomes in health administrative data can provide important insights into underlying physiological and behavioural mechanisms. Data Sources: This work utilized Ontario health administrative data housed at the Institute for Clinical Evaluative Sciences (ICES). The study included all children born in Ontario, Canada between 2002 and 2011 (over 1 million children). Vaccinations were identified using OHIP fee for service billing codes for general vaccination. Admissions and ER visits for any reason were identified in the Discharge Abstract Database (DAD) and National Ambulatory Care Reporting System (NACRS). Primary reasons for admissions and ER visits were investigated using ICD-10-CA codes reported in the DAD and NACRS databases. Statistical Methods: The self-controlled case series design (SCCS) was used to calculate the relative incidence of admissions, ER visits and other AEFIs. To investigate relative incidence for AEFIs across risk groups of interest, as well as addressing the healthy vaccinee effect bias, RIRs were calculated. RIRs are the ratio of incidence ratios in a subgroup of interest relative to a designated reference group. Results and Conclusions: The combined approach of using the SCCS design and RIRs to identify risk factors and overcome the healthy vaccinee bias proved to be a powerful approach to studying vaccine safety. Future work will be important to characterize the performance and validity of the SCCS + RIR approach in the presence of increasing levels of confounding and differing manifestations of the healthy vaccinee bias, as well as to elucidate the biological and behavioural mechanisms underlying our findings.