Senior Scientist, Clinical Epidemiology, Ottawa Hospital Research Institute

My most significant contributions have been in the areas of (a) diagnosis of pulmonary embolism (PE) and deep vein thrombosis (DVT), (b) treatment and (c) meta-analysis. With respect to diagnosis, my most important work has been the introduction of clinical assessment in the diagnostic process for patients with suspected DVT or PE. Clinical assessment was felt to be irrelevant and of no use in the diagnostic process until our paper was published in the Lancet in 1995. In this study we were able to demonstrate that patients could be classified as low, moderate or high probability for DVT. This has subsequently led to an improvement in the diagnostic process in terms of safety, convenience and cost. Subsequent studies have demonstrated the utility of the clinical assessment in outpatients, inpatients and patients presenting to the emergency department. My research continues to build on this aspect of investigation. Many investigators now use the clinical model and it is widely quoted. We have carried this diagnostic work into the area of PE and developed a clinical model that has shown similar utility and this has been used in a management strategy. I have presented this work at international meetings and we have also demonstrated the utility of D-dimer testing in this group of patients. Most recently, we showed that we can eliminate diagnostic testing in the many patients with suspected DVT or PE who have a low clinical probability and a negative D-dimer.

We have published the largest randomized trial ever performed in patient with suspected DVT. This was recently published in the New England Journal and definitely demonstrated the utility of adding D-dimer testing to clinical probability in the diagnostic process.

I have also published several meta-analyses that have been important. In 1995, we were able to demonstrate that there is a significant difference in the accuracy of ultrasound for the diagnosis of patients with asymptomatic DVT in post-operative patients. This study started a paradigm change in interpretation of diagnostic tests that sensitivity and specificity of a diagnostic can vary between patient populations and led to a better understanding of the fact that asymptomatic and symptomatic DVT are different diseases. This knowledge has led to an appreciation that DVT developing post-operatively have a very different natural history than symptomatic DVT and has led to another paradigm shift. Symptomatic DVT, not those detected by venography post-op, are the relevant clinical issue. In one of my publications, with this paradigm shift it can be demonstrated that Warfarin is the most cost-effective method to prevent post-op DVT. In work with our collaborative group in a randomized trial, we demonstrated the utility of a Warfarin nomogram. The nomograms we have published have been adopted across the world and also in guidelines, including those recently published in Thorax 2003. (see publication list). Our group has also published the largest series on the use of low molecular weight heparin for acute venous thrombosis in pregnancy and we have been pioneers in the outpatient treatment of pulmonary embolism

In the areas of treatment of DVT and PE, I demonstrated that a wide spectrum of patients can be treated on an outpatient basis. The importance of expanding the eligibility of outpatient treatment is that we now know it is safe to treat the vast majority of patients with DVT or PE on an outpatient basis and this is becoming the norm worldwide. Previous studies had enrolled selected and limited numbers of patients for outpatient therapy. As importantly, in a study performed with my then graduate student, Marc Rodger, we demonstrated that low molecular weight heparin is more cost effective than unfractionated heparin. In the later case, this conclusion holds true even if patients are treated as outpatients with unfractionated heparin. This has eased the transition to low molecular weight heparin in venous thrombosis in institutions across Canada. We have since demonstrated in a large randomized controlled trial that there are no differences between low molecular weight heparin preparations (submitted to Annals of Internal Medicine). More recently, I have looked at trying to predict bleeding risk (Arch Intern Med 2003) and VTE recurrence. More recently, our work is also involving genetic thrombophilias. Through rigorous study design, we have demonstrated that the ACE gene is protective against venous thrombosis. We have also demonstrated by a systematic review, accurate rates of venous thromboembolic events in first degree relatives of patients with a thrombophilia. This is forming the foundation for a larger trial, a study that we are currently performing in a pilot format.

Future Research:

Dr. Wells is Professor of Medicine and Canada Research Chair who has been performing research in venous thromboembolic diseases for over a decade now. He has participated in several large clinical trials which have required collections of bios samples. Through his Canada Research Chair, he established a genetics research lab in conjunction with molecular biologist, Dr. Frederique Tesson. This laboratory has already been involved in the collection of samples and DNA assays in the ACE study which was a case control study of over 300 cases and controls involving idiopathic venous thrombosis. He has also been collecting samples throughout the conduct of the First Degree Relative (FDR) pilot study funded by CIHR. Dr. Nancy Carson, molecular biologist, co-supervises Dr. Wells' laboratory with him and is responsible for quality assurance of assays. Dr. Wells is also the Director of a Program Grant, recently funded by Heart and Stroke Foundation of Ontario, which endeavours to perform research in the area of thrombophilia. This research will carry through all of the four so-called pillars of the CIHR, including gene discovery right through to policy management. This is the mandate of Dr. Wells' research chair and the Program Grant and this grant fits in perfectly with this mandate. So the resources provided to the Program Grant will ensure the smooth running of this proposed application and will, hopefully, enable future projects to evolve out of it.

Major Awards:

Grants Currently Held:

Most Recent Publications (provided by The Ottawa Hospital Library Database)

Note: This is not a complete list of publications. More publications may be available in The Ottawa Hospital Library database and Pubmed (search by last name and initials).