5.1. Literature Search Strategy

The literature search was performed by an information specialist using a peer-reviewed search strategy.

Published literature was identified by searching the following bibliographic databases: MEDLINE (1946 to present) with in-process records and daily updates via Ovid; Embase (1980 to present) via Ovid; The Cochrane Library (2011, Issue 5) via Wiley; and PubMed. The search strategy comprised both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were warfarin and specialized anticoagulation services. Keywords were searched in title only and controlled vocabulary restricted to major subject headings.

Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, and non-randomized studies. Conference abstracts were excluded from the search results. Where possible, retrieval was limited to the human population. Retrieval was also limited to documents published between January 1, 2006, and May 31, 2011. The initial search was completed on May 31, 2011. Regular alerts were established to update the search until the publication of the final report.

Additionally, a search on warfarin and atrial fibrillation was conducted using the same databases listed above. Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, and guidelines. Retrieval was also limited to documents published between January 1, 2006, and May 12, 2011. The initial search was completed on May 12, 2011. Regular alerts were established to update the search until the publication of the final report.

Grey literature (literature that is not commercially published) was identified by searching the health technology assessment agencies and guidelines sections of the Grey Matters checklist (www.cadth.ca/resources/grey-matters). Google and other Internet search engines were used to search for additional web-based materials. These searches were supplemented by reviewing the bibliographies of key papers and through contacts with appropriate experts and industry.

The authors of this report also consulted the primary authors of the upcoming 2012 American College of Chest Physicians (ACCP) guidelines on management of anticoagulation therapy.

5.2. Selection Criteria and Method

Two reviewers (CK and AK) independently screened citations and selected health technology assessments (HTAs), systematic reviews, meta-analyses, randomized controlled trials, and non-randomized studies regarding specialized anticoagulation services for management of warfarin dosing. The decision to order an article was based on the title and abstract, where available. In cases of insufficient information, the article was ordered. The same two reviewers selected the final articles for inclusion based on full-text publications. An article was included for review according to selection criteria established a priori (Table 1). Any disagreement between reviewers was discussed until consensus was reached.

Table 1

Selection Criteria.

5.3. Exclusion Criteria

Studies were excluded if they did not meet the selection criteria; focused only on patients with mechanical heart valves; were narrative reviews or editorials; were performed in a pediatric population; or were included in a selected HTA, systematic review, or meta-analysis. Additionally, systematic reviews were excluded if all reviewed studies were included in a more recent systematic review or meta-analysis.

5.4. Data Extraction Strategy

One reviewer (CK) extracted clinical effectiveness data for each article to tabulate relevant characteristics and outcomes from the included studies. Data extraction was verified by a second reviewer (AK) to confirm accuracy.

5.5. Critical Appraisal of Individual Studies

Two reviewers (CK and AK) independently appraised the included studies. The quality of systematic reviews was evaluated using the AMSTAR instrument.¹³ The quality of randomized controlled trials (RCTs) and non-randomized studies was assessed using the Downs and Black instrument.¹⁴ Methodological quality of clinical effectiveness evidence was evaluated based on randomization, adequate concealment of randomization, degree of blinding, use of intention to treat analysis, and description of dropouts and withdrawals, where appropriate. A numeric score was not calculated for each study; instead, strengths and weaknesses are described. Any disagreements were resolved through discussion until consensus was reached.

5.6. Data Analysis Methods

Because of heterogeneity present across the selected studies, a formal meta-analysis was not conducted. Studies were described using a narrative approach.