Harmonization of the Health and Risk Factor Questionnaire data of the Canadian Partnership for Tomorrow Project: a descriptive analysis.

BACKGROUND: The Canadian Partnership for Tomorrow Project is a multistudy platform integrating the British Columbia Generations Project, Alberta's Tomorrow Project, the Ontario Health Study, CARTaGENE (Quebec) and the Atlantic Partnership for Tomorrow's Health. This paper describes the process used to harmonize the Health and Risk Factor Questionnaire data and provides an overview of the key information required to properly use the core data set generated. METHODS: This is a descriptive analysis of the harmonization process that was developed on the basis of the Maelstrom Research guidelines for retrospective harmonization. Core variables (DataSchema) to be generated across cohorts were defined and the potential for cohort-specific data sets to generate the DataSchema variables was assessed. Where relevant, algorithms were developed and applied to process cohort-specific data into the DataSchema format, and information to be provided to data users was documented. RESULTS: The Health and Risk Factor Questionnaire DataSchema (version 2.0, October 2017) comprised 694 variables. The assessment of harmonization potential for the variables over 12 cohort-specific data sets resulted in 6799 (81.6%) of the variables being considered as harmonizable. A total of 307 017 participants were included in the harmonized data set. Through the cohort data portal, researchers can find information about the definitions of variables, harmonization potential, algorithms applied to generate harmonized variables and participant distributions. INTERPRETATION: The harmonization process enabled the creation of a unique data set including data on health and risk factors from over 307 000 Canadians. These data, in combination with complementary data sets, can be used to investigate the impact of biological, environmental and behavioural factors on cancer and chronic diseases.

The Canadian Partnership for Tomorrow Project: a pan-Canadian platform for research on chronic disease prevention.

BACKGROUND: Understanding the complex interaction of risk factors that increase the likelihood of developing common diseases is challenging. The Canadian Partnership for Tomorrow Project (CPTP) is a prospective cohort study created as a population-health research platform for assessing the effect of genetics, behaviour, family health history and environment (among other factors) on chronic diseases. METHODS: Volunteer participants were recruited from the general Canadian population for a confederation of 5 regional cohorts. Participants were enrolled in the study and core information obtained using 2 approaches: attendance at a study assessment centre for all study measures (questionnaire, venous blood sample and physical measurements) or completion of the core questionnaire (online or paper), with later collection of other study measures where possible. Physical measurements included height, weight, percentage body fat and blood pressure. Participants consented to passive follow-up through linkage with administrative health databases and active follow-up through recontact. All participant data across the 5 regional cohorts were harmonized. RESULTS: A total of 307 017 participants aged 30-74 from 8 provinces were recruited. More than half provided a venous blood sample and/or other biological sample, and 33% completed physical measurements. A total of 709 harmonized variables were created; almost 25% are available for all participants and 60% for at least 220 000 participants. INTERPRETATION: Primary recruitment for the CPTP is complete, and data and biosamples are available to Canadian and international researchers through a data-access process. The CPTP will support research into how modifiable risk factors, genetics and the environment interact to affect the development of cancer and other chronic diseases, ultimately contributing evidence to reduce the global burden of chronic disease.

Maelstrom Research guidelines for rigorous retrospective data harmonization.

Background: It is widely accepted and acknowledged that data harmonization is crucial: in its absence, the co-analysis of major tranches of high quality extant data is liable to inefficiency or error. However, despite its widespread practice, no formalized/systematic guidelines exist to ensure high quality retrospective data harmonization. Methods: To better understand real-world harmonization practices and facilitate development of formal guidelines, three interrelated initiatives were undertaken between 2006 and 2015. They included a phone survey with 34 major international research initiatives, a series of workshops with experts, and case studies applying the proposed guidelines. Results: A wide range of projects use retrospective harmonization to support their research activities but even when appropriate approaches are used, the terminologies, procedures, technologies and methods adopted vary markedly. The generic guidelines outlined in this article delineate the essentials required and describe an interdependent step-by-step approach to harmonization: 0) define the research question, objectives and protocol; 1) assemble pre-existing knowledge and select studies; 2) define targeted variables and evaluate harmonization potential; 3) process data; 4) estimate quality of the harmonized dataset(s) generated; and 5) disseminate and preserve final harmonization products. Conclusions: This manuscript provides guidelines aiming to encourage rigorous and effective approaches to harmonization which are comprehensively and transparently documented and straightforward to interpret and implement. This can be seen as a key step towards implementing guiding principles analogous to those that are well recognised as being essential in securing the foundational underpinning of systematic reviews and the meta-analysis of clinical trials.

Methodological gaps in the assessment of risk minimization interventions: a systematic review.

INTRODUCTION: Since the introduction of therapeutic risk management regulatory guidance, an increase in the number of risk minimization interventions (RMIs) published in the literature has been observed. Methods used to evaluate their effectiveness remain, however, poorly examined. OBJECTIVE: This paper aimed to conduct a literature review on the methods of evaluation of effectiveness of RMIs and to identify methodological gaps. METHODS: The search was conducted using MEDLINE and Embase between 1 January 2000 and 31 December 2010, and updated on 1 April 2013. The following characteristics were extracted from each study: target population for the RMI, target population for the assessment of effectiveness, study design, data sources, and effectiveness outcome(s). RESULTS: A total of 188 unique RMIs were identified in the literature, of which effectiveness was evaluated in only 65 (34.6%) at the time of publication. The largest proportion of studies reviewed (n = 49, 75.4%) attempted to evaluate changes in behavior through prescribing or laboratory test practices. One quarter of studies evaluated the effect of RMIs on the occurrence of adverse events. Only a minority of studies used robust designs, such as randomized controlled trials (n = 6, 9.2%) or a quasi-experimental design with a parallel comparison group (n = 8, 12.3%). CONCLUSION: Lack of robust methodological design used in published studies on RMI effectiveness evaluation is an important methodological gap in the evaluation of RMI effectiveness. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Impact of regulatory guidances and drug regulation on risk minimization interventions in drug safety: a systematic review.

BACKGROUND: Therapeutic risk management has received growing interest in recent years, particularly since the publication of regulatory guidances in 2005 and 2006, paralleled with a change in drug regulation. The characteristics of risk minimization interventions (RMIs) that have been implemented or approved remain inadequately explored. OBJECTIVE: The aim of this study was to review RMIs published in the literature or posted on regulatory agency websites over the past 10 years, and to assess whether publication of regulatory guidances on risk management is associated with changes in the number and types of interventions. METHODS: Sources were searched for RMIs published/posted between 1 January 2000 and 31 December 2009. For the literature search, MEDLINE and EMBASE databases were used using key words related to drug safety (i.e. 'drug toxicity') and the individual RMI names. The website review involved searches of major regulatory authority websites such as the European Medicines Agency, US FDA, Health Canada, the UK's Medicines and Healthcare products Regulatory Agency, Japan's Pharmaceutical and Medical Devices Agency and Australia's Therapeutic Goods Administration. The following eligibility criteria were applied for inclusion in the review: published/posted between the years 2000 and 2009, inclusive; involving drug products; use in humans; and involving RMIs, or tools used to increase the reporting of adverse events (AEs). Natural healthcare products, devices, diagnostic chemicals, pregnancy registries without follow-up, medication errors and products not used as therapy for illness were not retained. For each source, the following characteristics were extracted: nature of the intervention, target population, therapeutic area, AE(s) of special interest, country/regulatory agency and year of publication. RESULTS: A total of 119 unique interventions were identified in the literature (54 published in 2000-4 and 65 published in 2005-9). Interventions included educational material (n = 37; 31%), black-box warnings (n = 22; 19%) and therapeutic drug monitoring (n = 11; 9%). The website review produced a total of 1112 interventions: 326 posted between the years 2000 and 2004, and 786 between the years 2005 and 2009. The main interventions observed were: educational material (n = 956; 86%), black-box warnings (n = 45; 4%) and withdrawals (n = 39; 4%). LIMITATIONS: Additional regulatory resource websites were available in the post-guidances periods that were not available in the earlier years of the pre-guidances periods, and may bias the post-guidances results. Also, not all global regulatory websites were searched. Finally, only English-language websites were searched, limiting the variation of RMIs observed. Classification and categorizing for this particular review may not be consistent with future reviews by other researchers. CONCLUSION: The US is the sole region with a substantial increase in published RMIs during the post-guidances period, while the EU, Japan and the US all indicated an increase in the number of interventions on their websites.

Impact of guideline-consistent therapy on outcome of patients with healthcare-associated and community-acquired pneumonia.

BACKGROUND: A new category of healthcare-associated pneumonia (HCAP) has been added in the most recent American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines, since multidrug-resistant (MDR) pathogens are more common in patients with HCAP than in those with community-acquired pneumonia (CAP). The optimal empirical management of patients with HCAP remains controversial and adherence to guidelines is inconsistent. METHODS: A retrospective cohort study of 3295 adults admitted for pneumonia in an academic centre of Canada, between 1997 and 2008. RESULTS: MDR pathogens were more common among patients with HCAP than in those with CAP, but less so than in other studies. Compared with patients with CAP, those with HCAP had a higher all-cause 30 day mortality [68/563 (12%) versus 201/2732 (7%); P < 0.001] and more frequent need for mechanical ventilation [78/563 (14%) versus 276/2732 (10%); P = 0.01]. In patients with CAP, mortality was lower when treatment was concordant with guidelines [86/1557 (6%) versus 109/1097 (10%) if discordant; adjusted odds ratio 0.6 (0.4-0.8); P < 0.001]. In HCAP, mortality was similar whether or not empirical treatment was concordant with guidelines [6/35 (17%) versus 18/148 (12%) if discordant; P = 0.4]. However, 30 day mortality tended to be higher when the empirical treatment was microbiologically ineffective [4/22 (18%) versus 17/187 (9%) when effective; P = 0.3]. CONCLUSIONS: HCAP is associated with worse outcomes than CAP. MDR pathogens were implicated in only a small fraction of HCAP cases. In our study, unlike CAP, non-respect of current HCAP guidelines had no adverse effect on the ultimate outcome. Strategies for the empirical management of HCAP should be tailored to the local epidemiological context.