Volume 20, Issue 2, Fall/Winter 2020

Project Update

Deeper Insights into Health – Data Linkage with Alberta’s Tomorrow Project

Your daily activities, such as eating, sleeping and physical exercise, can have great impact on your health. By filling out health and lifestyle questionnaires, participants of Alberta’s Tomorrow Project (ATP), the largest population-based cohort study of cancer and chronic diseases in Alberta, provided unique information on individual lifestyle behaviours and disease risk factors. This information about personal behaviours cannot be easily obtained from other data sources, and is an important contribution to help people understand the underlying causes leading to chronic conditions like cardiovascular disease, diabetes and cancer.

The ATP cohort began in 2000 and is led by a team based in Alberta Health Services. Over 50,000 Albertans participate in this project. In 2008, ATP joined forces with other regional cohorts to create a nation-wide research platform known as the Canadian Partnership for Tomorrow’s Health (CanPATH; https://canpath.ca/). More details of ATP can be found at www.myATP.ca.

How can we make the ATP cohort data even more valuable for the study of chronic diseases? Almost all – more than 99% - of ATP participants have given consent to link their personal behavioral and risk factor survey data to other health-related records. With the support of Alberta Health (AH), the Ministry of Health in Alberta, ACHORD has partnered with ATP to build an Alberta-based research platform for cancer and chronic disease study by linking multiple health data sources to the ATP cohort. These health datasets include AH clinical and healthcare data, Alberta Precision Laboratories (APL) diagnostic laboratory data, Alberta Cancer Registry (ACR) cancer diagnosis and treatment data and the Canadian Urban Environmental Health Research Consortium (CANUE) socio-geographic data.

By linking all these health data together with the ATP cohort, researchers in Alberta can easily access anonymous, de-identified individual level healthcare data, such as doctors’ visits, medication, diagnosis and health outcomes, along with patients’ individual lifestyles, biomarker data, socio-economic status, socio-geographic and environmental factors. ATP research using multiple data sources linked by the ACHORD can provide clinicians and policy makers with a holistic view of how personal lifestyle behaviors, social and environmental factors and healthcare systems interact with each other to influence the health and wellness of Albertans. Linking and co-analyzing the ATP lifestyle and risk factor data with other health-related data has greatly enhanced the research capacity of ATP to study cancer and chronic diseases. The following is a list of publications arising from this ACHORD-ATP partnership, using the ATP cohort data linked with multiple health datasets.

Meet The Students

Recent Literature from the ACHORD Journal Club

(Paper discussed Tuesday, November 3, 2020; Commentary by Sabrina Saba)

Sesso HD, Christen WG, Bubes V, et al. Multivitamins in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Controlled Trial. JAMA. 2012;308(17):1751–1760. PMID: 23117775

Article Summary:
The popularity of multivitamins has increased rapidly in the past few decades, and currently, multivitamins are one of the most commonly used supplements in the world. While there is still uncertainty regarding the long-term health benefits of vitamins, adults continue to take vitamin supplements with the belief that they may prevent chronic diseases or improve general health and wellbeing. The authors describe the possible financial implications of chronic supplement consumption, as well as the concern that individuals who believe they are deriving benefits from supplements may be less likely to engage in other preventive health behaviors. This study specifically explored heart disease, the leading cause of death worldwide, for which evidence of the preventative role of multivitamins is mixed.

For more than a decade, the Physicians’ Health Study II (PHS ll), a randomized controlled trial, investigated the effects of daily multivitamin use in over 14,000 male doctors over the age of 50. In this paper, the authors wanted to find out the effect of multivitamin use on major cardiovascular events. The paper considered all clinically important outcomes. The primary endpoint was major cardiovascular disease (CVD) (fatal and non-fatal stroke, myocardial infarction or CVD death)) and secondary endpoints were total MI, total stroke (fatal and non-fatal), CV death alone, ischemic and hemorrhagic stroke, and total mortality. Other major endpoints, such as cancer, were assessed and reported in a different paper. The authors did not use any surrogates as they only looked at the hard clinical endpoints. Morbidity and mortality follow-up in PHS II were high—98.2% and 99.9%, respectively. In addition, morbidity and mortality follow-up as a percentage of person-time each exceeded 99.9%. Adherence with the multivitamin component was defined from participant self-report, which has been shown to be highly reliable in physicians, as taking at least two-thirds of the pills.

For the primary endpoint, the hazard ratio (HR) for multivitamin vs placebo was 1.01. This effect is extremely small, non-significant and clinically inconsequential. The risk ratio (RR) is 1.02, that is clinical and statistically non-significant (11.98% of major CVD in multivitamin group and 11.69% in placebo group). In terms of absolute risk reduction (ARR), there was none. The AR was higher in the multivitamin arm compared to placebo. The confidence interval (CI) was 0.91 to 1.10. The 95% CI were reasonably precise but given the sample size, we would have expected a smaller CI. So the true effect could range from a 9% reduction in major CVD to a 10% increase; both of these are well below the 20% rule and so the results are likely not important. The authors conclude that among the population of US male physicians followed for more than a decade, consumption of a daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality. With no clinical benefits observed, it may not be worth the costs to the province, and there may also be unintended harms to consider.

Discussion Within Journal Club:
We first discussed internal and external validity of research, and the trade-off that emerges between the value of a study with a high level of internal validity (such as this RCT, with carefully controlled variables) and the value of a study that may be more externally valid (generalizable to the somewhat less controlled environment of the “real world”). For example, as this study’s population consisted of male physicians over the age of 50, the information gained from this study is clearly a good fit for males from a higher socioeconomic class. As such, the selective generalizability of this study made this a perfect example of a well-preserved internally valid but externally invalid study. We then asked which was better – a study that is internally valid, or a study that is externally valid – and the importance of internal validity as a first step. Without trustworthy, internally valid results, external validity becomes irrelevant.

We also considered the difference between confounding (a “nuisance” variable associated with both the outcome and the exposure, accounting for some of the perceived effect) and effect modification (a variable that affects the outcome, but not the exposure; stratification is helpful). In terms of follow-up, we talked about the 5/20% rule of thumb. The study indicated <5% events not record that would suggest that follow-up was very good for a 10-15 year trial and it is below our 5/20% rule. We also discussed that there was no differential losses to follow-up. On the other hand, even if there is some differential losses for the non-fatal events, the impact is likely minimal on the study results. We had a brief discussion about intention-to-treat (ITT) analysis and how loss to follow-up can affect the analysis, and how ITT is different from per-protocol analysis. We agreed that there is no arguing that multivitamins are important when nutritional requirements are not met through diet alone (for example, if there is a nutritional deficit), but, if in the absence of clinically important deficits, then multivitamins might very well pose an unnecessary financial burden and health expenditure.

ACHORD Seen and Heard

Recent Publications

Boisvenue JJ, Oliva CU, Manca DP, Johnson JA, Yeung RO. Feasibility of identifying and describing the burden of early-onset metabolic syndrome in primary care electronic medical record data: a cross-sectional analysis. CMAJ Open 2020;8(4):e779-e787. PMID: 33234585

Campbell SA, Light PE, Simpson SH. Costarting sitagliptin with metformin is associated with a lower likelihood of disease progression in newly treated people with type 2 diabetes: a cohort study. Diabet Med 2020;37(10):1715-1722. PMID: 31618475

Diabetes Canada Clinical Practice Guidelines Expert Committee, Lipscombe L, Butalia S, Dasgupta K, Eurich DT, MacCallum L, Shah BR, Simpson S, Senior PA. Pharmacologic Glycemic Management of Type 2 Diabetes in Adults: 2020 Update. Can J Diabetes 2020;44(7):575-591. PMID: 32972640

Dubois TB, Simpson SH, Eurich DT. Time to Treatment Intensification in Newly Treated Adult Type 2 Diabetes Patients: Comparison of Canada and the United States. Can J Diabetes 2020;44(4):312-316. PMID: 31831258

Hall JJ, Eurich DT, Nagy D, Tjosvold L, Gamble JM. Thiazide Diuretic-Induced Change in Fasting Plasma Glucose: a Meta-analysis of Randomized Clinical Trials. J Gen Intern Med 2020;35(6):1849-1860. PMID: 32157653

Mazaroff S, Veugelers PJ, Dabravolskaj J, Eurich DT, Ye M, Maximova K. Diet Quality and Health Service Utilization for Depression: A Prospective Investigation of Adults in Alberta’s Tomorrow Project. Nutrients 2020;12(8):2437. PMID: 32823652

Necyk C, Johnson JA, Minhas-Sandhu J, Tsuyuki RT, Eurich DT. Evaluation of comprehensive annual care plans by pharmacists in Alberta for patients with complex conditions. J Am Pharm Assoc (2003) 2020;60(6):1029-1036. PMID: 32962900

Soprovich AL, Seaton CL, Bottorff JL, Duncan MJ, Caperchione CM, Oliffe JL, James C, Rice S, Tjosvold L, Eurich DT, Johnson ST. A systematic review of workplace behavioral interventions to promote sleep in men. Sleep Health 2020;6(3):418-430. PMID: 32461158

Thomas S, Johnson JA, Xie F. 3125 steps to perfect health: a nonparametric approach to developing the EQ-5D-5L value set. Qual Life Res 2020;29(11):3109-3118. PMID: 32705459

Meeting Presentations and Invited Talks

Eurich DT. Edmonton zone makes up almost 66% of new COVID-19 cases in Alberta, experts plead for public health measures to be followed. Global News. August 19, 2020.

Eurich DT. Hockey Edmonton prepares for return to play under COVID-19 pandemic. CBC News August 22, 2020.

Eurich DT. Second wave hasn't arrived in Alberta yet, epidemiologists say, but surge likely coming. Calgary Herald, September 24, 2020.

Eurich DT. Edmonton docs describe hospital horrors — and Calgary counterpart says city is next. Calgary Herald, November 21, 2020.

Eurich DT. Alberta logs record-high 1,336 COVID-19 cases; One per cent of Albertans have now tested positive. Calgary Herald, November 22, 2020.

ACHORD Accolades

Congratulations to:

Other ACHORD News

Congratulations to Nathan McClure on his marriage to Lindsay McInnes in August.

ACHORD
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email: achord@ualberta.ca
Phone: 780-248-1010