Developing a Canadian Real-World Evidence Action Plan across the Drug Life Cycle.

Policy makers face challenges with the number of drugs for rare indications and rapidly rising costs. In facing these challenges, decision-makers see real-world evidence (RWE) as an opportunity. Health Canada and the Canadian Agency for Drugs and Technologies in Health (CADTH) recently announced their intent to co-develop an action plan to optimize the process for the systematic use and integration of RWE into both regulatory and reimbursement decision-making in Canada. When implemented, this will have a significant impact on how drugs are approved and paid for in Canada. We highlight the key opportunities, barriers and future directions related to the use of RWE throughout the life cycle of drugs in Canada.

Genital herpes in Canada: Deciphering the hidden epidemic.

INTRODUCTION: Genital herpes (GH) is the most common cause of genital ulceration, but is not reportable in Canada. Research in the United States has found that less than 10% of seropositive persons reported a diagnosis of GH. The present article investigates the rates of diagnosed cases of GH in Canada from 2002 to 2007. METHODS: Primary case diagnosis data on GH for the period between 2002 and 2007 were obtained from the Canadian Disease and Therapeutic Index, a proprietary database maintained by Intercontinental Medical Statistics (IMS) Health Canada. Of the 45,000 to 49,000 office-based physicians in Canada, IMS Health collected diagnosis-specific prescription diaries from a sample of 652, stratified according to geographic region and representing all major specialties, during this period. RESULTS: Between 2002 and 2007, there were approximately 84,398 to 122,456 medically attended GH cases annually in Canada. Approximately 74% to 93% of these diagnosed cases made one physician visit per year. The annual rate of medically attended GH cases ranged from 261.2 per 100,000 population to 386.6 per 100,000 population. DISCUSSION: The present report is the first time that administrative data have been used to estimate the annual rate of medically attended GH cases in Canada. The data include both incident and prevalent cases and are likely an underestimate of the actual number of cases because they only represent diagnosed cases presenting for medical care. Further seroepidemiological and clinical research studies would be helpful to assess the burden of infection and to plan appropriate diagnostic, treatment and preventive counselling services. INTRODUCTION: Genital herpes (GH) is the most common cause of genital ulceration, but is not reportable in Canada. Research in the United States has found that less than 10% of seropositive persons reported a diagnosis of GH. The present article investigates the rates of diagnosed cases of GH in Canada from 2002 to 2007. METHODS: Primary case diagnosis data on GH for the period between 2002 and 2007 were obtained from the Canadian Disease and Therapeutic Index, a proprietary database maintained by Intercontinental Medical Statistics (IMS) Health Canada. Of the 45,000 to 49,000 office-based physicians in Canada, IMS Health collected diagnosis-specific prescription diaries from a sample of 652, stratified according to geographic region and representing all major specialties, during this period. RESULTS: Between 2002 and 2007, there were approximately 84,398 to 122,456 medically attended GH cases annually in Canada. Approximately 74% to 93% of these diagnosed cases made one physician visit per year. The annual rate of medically attended GH cases ranged from 261.2 per 100,000 population to 386.6 per 100,000 population. DISCUSSION: The present report is the first time that administrative data have been used to estimate the annual rate of medically attended GH cases in Canada. The data include both incident and prevalent cases and are likely an underestimate of the actual number of cases because they only represent diagnosed cases presenting for medical care. Further seroepidemiological and clinical research studies would be helpful to assess the burden of infection and to plan appropriate diagnostic, treatment and preventive counselling services.

INTRODUCTION: L'herpès génital (HG) est la principale cause d'ulcération génitale, mais il n'est pas à déclaration obligatoire au Canada. D'après des recherches menées aux États-Unis, moins de 10 % des personnes séropositives ont déclaré un diagnostic d'HG. Le présent article porte sur le taux de cas d'HG diagnostiqués au Canada entre 2002 et 2007. MÉTHODOLOGIE: Les chercheurs ont obtenu les données diagnostiques des cas primaires d'HG entre 2002 et 2007 dans l'Index canadien des maladies et traitements, une base de données commerciale qu'exploite Intercontinental Medical Statistics (IMS) Health Canada. Pendant cette période, IMS Health a colligé les carnets de prescriptions propres aux diagnostics auprès d'un échantillon de 652 des 45 000 à 49 000 médecins en pratique privée du Canada, stratifié selon la région géographique et représentant toutes les grandes spécialités. RÉSULTATS: Entre 2002 et 2007, on a recensé chaque année de 84 398 à 122 456 cas d'HG suivis par un médecin au Canada. De 74 % à 93 % de ces cas diagnostiqués rendaient visite au médecin une fois par année. Le taux annuel de cas d'HG suivis par un médecin oscillait entre 261,2 personnes sur 100 000 habitants et 386,6 personnes sur 100 000 habitants. EXPOSÉ: On expose pour la première fois, dans le présent rapport, le recours à des données administratives pour évaluer le taux annuel de cas d'HP suivis par un médecin au Canada. Les données incluent à la fois les cas incidents et prévalents et, selon toute probabilité, elles sous-évaluent le véritable nombre de cas, car elles représentent seulement les cas diagnostiqués qui consultent pour obtenir des soins médicaux. Il serait utile de mener d'autres projets de recherche systématiques, nationaux, séroépidémiologiques et cliniques pour évaluer le fardeau de l'infection et planifier des services diagnostiques, thérapeutiques et préventifs pertinents.

Feasibility of incorporating self-collected rectal swabs into a community venue-based survey to measure the prevalence of HPV infection in men who have sex with men.

BACKGROUND: Inclusion of self-collected rectal swabs (SCRS) into existing community venue-based HIV surveillance systems for men who have sex with men (MSM) may provide a feasible method for monitoring human papillomavirus (HPV) vaccine-related outcomes in this population. We measured the prevalence of HPV and anal dysplasia through incorporating SCRS into ManCount, the Vancouver site of the M-Track HIV surveillance system. METHODS: Participating MSM were provided with a self-collection kit for collection on-site or at a follow-up venue. Swabs were subject to polymerase chain reaction amplification for HPV detection, and cytology slides were reviewed for anal dysplasia. Factors associated with participation were identified through multivariate logistic regression. RESULTS: Of 766 men completing ManCount, 268 (35%) agreed to participate, self-collecting 252 specimens (247 on-site). Of 239 complete specimens, 33.5% did not have detectable ß-globin; in the remainder (159 specimens) the prevalence of HPV infection was 62.3% (23.3% HPV type 16 or 18; 38.4% HPV type 6, 11, 16, or 18). In the 62.3% (149) of specimens adequate for cytology, the prevalence of anal dysplasia was 42.3% (HSIL 11.4%, LSIL 18.8%, ASC-US 6.7%, ASC-H 5.4%). Participation was associated with venue type, availability of on-site collection, and other characteristics. CONCLUSIONS: SCRS can be feasibly integrated within existing community venue-based HIV surveillance systems for MSM, and may be a suitable method for monitoring the impact of HPV vaccination in this population. However, participation may be influenced by venue type and availability of on-site collection, and adequacy of SCRS specimens may be lower in community venues as compared with clinical settings.

Pandemic (H1N1) 2009 outbreak at Canadian Forces cadet camp.

We conducted a case-control study to describe the clinical and epidemiologic characteristics of an outbreak of pandemic (H1N1) 2009 at a Canadian military cadet training center. We found that asthma and obesity confer greater risk for infection. Viral shedding was detected by PCR up to 18 days after symptom onset.

Risk of severe outcomes among patients admitted to hospital with pandemic (H1N1) influenza.

BACKGROUND: We describe the disease characteristics and outcomes, including risk factors for admission to intensive care unit (ICU) and death, of all patients in Canada admitted to hospital with pandemic (H1N1) influenza during the first five months of the pandemic. METHODS: We obtained data for all patients admitted to hospital with laboratory-confirmed pandemic (H1N1) influenza reported to the Public Health Agency of Canada from Apr. 26 to Sept. 26, 2009. We compared inpatients who had nonsevere disease with those who had severe disease, as indicated by admission to ICU or death. RESULTS: A total of 1479 patients were admitted to hospital with confirmed pandemic (H1N1) influenza during the study period. Of these, 1171 (79.2%) did not have a severe outcome, 236 (16.0%) were admitted to ICU and survived, and 72 (4.9%) died. The median age was 23 years for all of the patients, 18 years for those with a nonsevere outcome, 34 years for those admitted to ICU who survived and 51 years for those who died. The risk of a severe outcome was elevated among those who had an underlying medical condition and those 20 years of age and older. A delay of one day in the median time between the onset of symptoms and admission to hospital increased the risk of death by 5.5%. The risk of a severe outcome remained relatively constant over the five-month period. INTERPRETATION: The population-based incidence of admission to hospital with laboratory-confirmed pandemic (H1N1) influenza was low in the first five months of the pandemic in Canada. The risk of a severe outcome was associated with the presence of one or more underlying medical conditions, age of 20 years or more and a delay in hospital admission.

Perceptions of smoking-related risks and benefits as predictors of adolescent smoking initiation.

OBJECTIVES: The predictive value of perceptions of smoking-related risks and benefits with regard to adolescent smoking initiation has not been adequately established. We used prospective, longitudinal data to directly test whether smoking-related perceptions predict smoking initiation among adolescents. METHODS: We administered surveys assessing perceptions of smoking-related risks and benefits to 395 high school students, beginning at the start of their ninth-grade year. We conducted follow-up assessments every 6 months until the end of 10th grade, obtaining 4 waves of data. RESULTS: Adolescents who held the lowest perceptions of long-term smoking-related risks were 3.64 times more likely to start smoking than were adolescents who held the highest perceptions of risk. Adolescents who held the lowest perceptions of short-term smoking-related risks were 2.68 times more likely to initiate. Adolescents who held the highest perceptions of smoking-related benefits were 3.31 times more likely to initiate. CONCLUSIONS: Findings from this study provide one of the first sets of empirical evidence to show that smoking initiation is directly related to smoking-related perceptions of risks and benefits. Thus, efforts to reduce adolescent smoking should continue to communicate the health risks of smoking and counteract perceptions of benefits associated with smoking.

A comparison of perinatal HIV prevention opportunities for Hispanic and non-Hispanic women in California.

Using a semi-structured survey and convenience sample of pregnant/recently delivered Hispanic (n = 453) and non-Hispanic (n = 904) women in four California counties, this study compared rates of timely prenatal care (PNC) initiation, HIV test counseling, test offering, and test acceptance in PNC between Hispanic and non-Hispanic women. Hispanic women were less likely to report timely PNC initiation (69.3% vs. 80.4%, p < .0001), receiving test offer (69.5% vs. 76.7%, p = .002), and ever having been tested (77.3% vs. 87.9%, p < .0001) than non-Hispanic women. Hispanic women were more likely to report not knowing where to go (p = .04) and having no insurance (p < .001), transportation (p = .001), and child care (p = .007) as reasons for late PNC start. Both Hispanic and non-Hispanic women most commonly accepted a test offer for their health/health of their baby; Hispanic women were more likely to accept based on doctor/nurse recommendation (80.1% vs. 62.7%, p < .001). A quarter of Hispanic and non-Hispanic women reported they didn't feel they had a choice or that test was done automatically. Efforts to improve perinatal HIV prevention opportunities for all women in California are required. Furthermore, Hispanic women may have disparities in receipt of prenatal care and HIV test offer that need additional attention.

Neonatal herpes simplex virus infections in Canada: results of a 3-year national prospective study.

OBJECTIVE: The goal was to determine incidence, determinants, and morbidity and mortality rates of neonatal herpes simplex virus infections in Canada. METHODS: From October 1, 2000, to September 30, 2003, reports of neonatal herpes simplex virus infection were solicited actively from all Canadian pediatricians and pediatric subspecialists on a monthly basis. RESULTS: Fifty-eight cases of neonatal herpes simplex virus were reported (5.9 cases per 100,000 live births). Cesarean section was performed in 24.6% of cases, 28.1% of patients were born prematurely, 28.6% had birth weights of < 2500 g, and 7.5% had Apgar scores of < 7 at 5 minutes of life. Mothers < 20 years of age and those reporting Aboriginal ethnicity were affected disproportionately; 40% of mothers had no history of genital herpes before delivery, and intrapartum genital lesions were present in only 1 of 58 cases. Of cases with known herpes simplex virus type, 62.5% were herpes simplex virus-1. Localized infections accounted for 59.6% of cases, whereas disseminated disease and central nervous system disease were reported for 17.5% and 22.8%, respectively. Localized infections were more likely to be herpes simplex virus-1 and disseminated and central nervous system infections herpes simplex virus-2. Nine of 58 cases were fatal. All cases with known treatment information (n = 55) were treated with intravenously administered acyclovir. CONCLUSIONS: This is the first study to examine the national incidence of neonatal herpes simplex virus in Canada. Many women had no genital herpes simplex virus history before delivery, and the majority of cases were herpes simplex virus-1, which has implications for prenatal screening and vaccine/drug development. Follow-up monitoring of case subjects is being performed annually for 3 years, to be completed in October 2006.

Oral versus vaginal sex among adolescents: perceptions, attitudes, and behavior.

OBJECTIVE: Despite studies indicating that a significant proportion of adolescents are having oral sex, the focus of most empirical studies and intervention efforts concerning adolescent sexuality have focused on vaginal intercourse. This narrow focus has created a void in our understanding of adolescents' perceptions of oral sex. This study is the first to investigate adolescents' perceptions of the health, social, and emotional consequences associated with having oral sex as compared with vaginal sex, as well as whether adolescents view oral sex as more acceptable and more prevalent than vaginal sex. METHODS: Participants were 580 ethnically diverse ninth-grade adolescents (mean age: 14.54; 58% female) who participated in a longitudinal study on the relationship between risk and benefit perceptions and sexual activity. Participants completed a self-administered questionnaire that inquired about their sexual experiences and percent chance of experiencing outcomes from, attitudes toward, and perceived prevalence of oral versus vaginal sex among adolescents. RESULTS: More study participants reported having had oral sex (19.6%) than vaginal sex (13.5%), and more participants intended to have oral sex in the next 6 months (31.5%) than vaginal sex (26.3%). Adolescents evaluated oral sex as significantly less risky than vaginal sex on health, social, and emotional consequences. Adolescents also believed that oral sex is more acceptable than vaginal sex for adolescents their own age in both dating and nondating situations, oral sex is less of a threat to their values and beliefs, and more of their peers will have oral sex than vaginal sex in the near future. CONCLUSIONS: Given that adolescents perceive oral sex as less risky, more prevalent, and more acceptable than vaginal sex, it stands to reason that adolescents are more likely to engage in oral sex. It is important that health care providers and others who work with youths recognize adolescents' views about oral sex and broaden their clinical preventive services to include screening, counseling, and education about oral sex.

Unique challenges to preventing perinatal HIV transmission among Hispanic women in California: results of a needs assessment.

To identify rates and factors associated with timely prenatal care (PNC) initiation, HIV test counseling, test offering, and test offer acceptance, we conducted a semistructured survey of a convenience sample of pregnant/recently delivered Hispanic women (n=453, 418 with analyzable data) in four California counties in 2000. Only 68.4% and 43.5% of Hispanic women reported receiving an HIV test offer and counseling, respectively, though 88.8% of those offered a test accepted. After controlling for the effects of age, education, years lived in the United States, health insurance coverage, delivery status, and parity, Hispanic women who initiated prenatal care in the first trimester were 1.7 times more likely to be offered an HIV test and almost 3 times more likely to receive counseling than women with a later prenatal care start or no prenatal care. Factors associated with timely PNC initiation on multivariate analysis were private/HMO insurance (OR=10.7, p < .001), Medi-Cal insurance (OR = 4.32, p < .001), being 25-30 years old (OR = 3.0, p = .008), and completion of high school (OR = 2.07, p = .01). Key opportunities to prevent perinatal HIV transmission are being lost for Hispanic women in California. Interventions to increase timely PNC initiation, and to improve test offering by health care providers, may help to improve counseling and testing rates for this population.

Report of the 2003 pan-Canadian forum on cervical cancer prevention and control.

OBJECTIVE: To develop evidence-based consensus recommendations on the delivery of cervical cancer screening, human papillomavirus (HPV) education, HPV testing, and the optimal tool for cervical cytology within the Canadian health system. PARTICIPANTS: Leading up to a forum held in Ottawa on November 21 and 22, 2003, 254 registrants reviewed position papers through a Web-based discussion group. Experts in program management, clinical practice, epidemiology, public health, economics, and women's health, representing 48 organizations, then participated in the 2-day forum to develop consensus recommendations. EVIDENCE: Writing groups prepared position papers on optimal methods for cervical cytology; education concerning HPV; HPV testing in primary screening; HPV testing as a triage tool in cytopathology; and delivery mechanisms for cervical screening. Systematic reviews were the primary source of evidence supplemented by literature searches. CONSENSUS PROCESS: Feedback from Web-based discussions was incorporated into consecutive drafts of position papers. At the forum, recommendations and supporting evidence were presented, further debated in small-group sessions, and discussed in a plenary session. Despite divergent professional mandates and opinions, consensus was achieved on 15 recommendations across all areas. Final recommendations were posted to the Web for further input and circulated for written consensus by participants. CONCLUSIONS: The recommendations cover the use of new evidence and technologies in cervical cancer prevention in Canada and provide a framework for provision of HPV education, planning the implementation of new cervical screening technologies in Canada, the development of evaluation plans, and new research areas.

Adolescents' beliefs about the risks involved in smoking "light" cigarettes.

BACKGROUND: Light cigarettes have been marketed by the tobacco industry as being a healthier smoking choice, a safe alternative to cessation, and a first step toward quitting smoking altogether. Research, however, has failed to show a reduction in smoking-related health risks, an increase in rates of smoking cessation, a decrease in the amount of carbon monoxide or tar released, or a reduction in the rates of cardiovascular disease or lung cancer associated with light cigarette use, compared with regular cigarette use. Nevertheless, more than one-half of adolescent smokers in the United States smoke light cigarettes. This study is the first to investigate adolescents' perception of the risks associated with smoking light cigarettes, as well as adolescents' attitudes and knowledge about the delivery of tar and nicotine, health risks, social effects, addiction potential, and ease of cessation with light cigarettes, compared with regular cigarettes. DESIGN: Participants were 267 adolescents (mean age: 14.0 years) who completed a self-administered questionnaire during class time. After reading scenarios in which they imagined that they smoked regular or light cigarettes, participants estimated the chances that they would personally experience 7 smoking-related health risks and 3 addiction risks. Participants also responded to 14 items concerning their attitudes and knowledge about light cigarettes versus regular cigarettes. RESULTS: Participants thought that they would be significantly less likely to get lung cancer, have a heart attack, die from a smoking-related disease, get a bad cough, have trouble breathing, and get wrinkles when smoking light cigarettes, compared with regular cigarettes, for the rest of their lives. Furthermore, when participants were asked how long it would take to become addicted to the 2 cigarette types, they thought it would take significantly longer to become addicted to light versus regular cigarettes. Adolescents also thought that their chances of being able to quit smoking were higher with light versus regular cigarettes. Similarly, when participants were asked how easy it would be to quit smoking the 2 cigarette types, they thought it would be significantly easier for them to quit smoking light cigarettes than regular cigarettes. Adolescents agreed or strongly agreed that regular cigarettes deliver more tar than light cigarettes and that light cigarettes deliver less nicotine than regular cigarettes. CONCLUSIONS: Overall, the results of this study show that adolescents hold misperceptions in both their personal risk estimates and their general attitudes about the health risks, addictive properties, and ease of cessation associated with light cigarettes. With a variety of light and ultralight cigarettes on the market, adolescents are led to think that there is a progression of safety levels to choose from when deciding which cigarettes to smoke. This illusion of control over health outcomes contributes to an underestimation of risks associated with smoking light cigarettes and supports these misperceptions. These results are of concern, given evidence suggesting that, if adolescents think they are less vulnerable to smoking-related health risks (ie, lung cancer), then they are more likely to initiate smoking. Furthermore, there is evidence that adolescents are not fully aware of the addictive nature of cigarettes and therefore think that they can experiment with smoking during adolescence without becoming addicted or experiencing any health consequences. The data presented here support concerns regarding smoking addiction; adolescents might be even more inclined to smoke light cigarettes to delay addiction. Without correct information about light cigarettes, adolescents are unable to make informed decisions about their smoking behaviors. The findings presented here strongly suggest that health care practitioners need to talk to their adolescent clients not only about the overall risks of smoking but also about the specific risks associated with smoking light cigarettes and other tobacco varieties, including the potential for addiction and long-term health consequences. Information shared with adolescents about light cigarettes, both individually by health care practitioners and at the population level via counter-advertising campaigns, may be successful in changing current misperceptions, and ultimately light cigarette smoking patterns, among youth.

Perceived risks and benefits of smoking: differences among adolescents with different smoking experiences and intentions.

BACKGROUND: Explanations of adolescent smoking often make reference to adolescents' beliefs that they are invulnerable to harm. However, empirical examination of whether adolescents do acknowledge risks. Further, few studies have considered perceived benefits in adolescents' behavioral decisions. This study examined perceived smoking-related physical and social risks and benefits between adolescents who have vs. have not smoked and do vs. do not intend to smoke. METHODS: Three hundred and ninety-five students (mean age = 14.0) completed a survey concerning their smoking experiences, intentions, and perceived risks and benefits of smoking. RESULTS: Adolescent smokers and those who intend to smoke estimated their chance of experiencing a smoking-related negative outcome as less likely than did nonsmokers and non-intenders. Smokers and intenders also reported the chance of addiction as less likely than did others. In contrast, adolescent smokers and intenders perceived the chance of experiencing a smoking-related benefit as more likely than did nonsmokers and non-intenders. CONCLUSIONS: The data suggest that rather than solely focusing on health risks as a way to deter adolescent smoking, the role of perceived social risks and benefits in adolescents' smoking may be an additional critical focus for intervention. In addition, efforts should be made to increase adolescents' awareness of the addictive nature of cigarettes.

Adolescents' self-efficacy to communicate about sex: its role in condom attitudes, commitment, and use.

This study examined whether and how self-efficacy to communicate with parents and peers about sex relate to sexually experienced adolescent males' and females' (N= 144, 112) condom attitudes, intentions, and use. Results showed that males who reported greater self-efficacy to communicate with parents used condoms more frequently; and both males and females who can communicate with peers used condoms more frequently. Self-efficacy to communicate with peers was related to more positive condom attitudes, which in turn were associated with greater condom commitment and use. Greater ability to communicate with parents was also related to greater condom commitment and use among males. These results suggest the importance of designing interventions that give adolescents the skills they need to feel efficacious in their ability to communicate about sex and contraception.