Patented Medicine Prices Review Board Research Articles

The impact of proposed price regulations on new patented medicine launches in Canada: a retrospective cohort study.

The Patented Medicine Prices Review Board (PMPRB), the agency that regulates the prices of patented medicines in Canada, published proposed amendments to the regulatory framework in December 2017. Because of a series of changes and delays, the revised policy has not yet been finalized. We sought to evaluate the potential early impact of the uncertainty about the PMPRB policy on patented-medicine launches. We developed a retrospective cohort of patented medicines (molecules) sold in Canada and the 13 countries that the PMPRB currently uses or has proposed to use as price comparators, from sales data from the IQVIA MIDAS database for 2012-2021. The outcome was whether a molecule was launched (i.e., sold) in a specific country within 2 years of its global first launch (2-yr launch). We compared the change of 2-year launch before (2012-2017) and after the proposed amendments were published ("uncertain period," 2018-2021) in Canada with the change in the United States and the other 12 countries as a group ("other-countries group"), using interrupted time series and logistic regressions, respectively. We further conducted analyses for each individual country and subgroups by molecule characteristics, such as therapeutic benefit, separately. We included 242 and 107 new molecules launched before publication of the proposed amendments and during the uncertain period, respectively. The corresponding 2-year launch proportions were 45.0% and 30.8% in Canada, 81.4% and 82.2% in the US, and 83.9% and 70.1% in the other-countries group. All analyses showed changes in 2-year launch during the uncertain period in the US and in the other-countries group that were similar to the changes in Canada. Greater decreases were observed in Norway and Sweden than in Canada. The 2-year launch proportion for molecules with major therapeutic benefit decreased from 45.8% to 31.3% in Canada during the uncertain period and from 87.5% to 62.5% in the other-countries group, but increased from 91.7% to 100% in the US. No negative impact of the PMPRB-policy uncertainty on molecule launches was observed when comparing Canada with price-comparator countries, except for molecules with major therapeutic benefit. The reduction in launches of medicines with major therapeutic benefit in Canada requires continuing investigation.

The impact of changing the reference countries on the list prices for patented medicines in Canada: A policy analysis

Background: Canada's Patented Medicine Prices Review Board (PMPRB) uses external and internal reference pricing (IRP) to regulate patented drug list prices. PMPRB has changed external reference countries from 7 to 11 to include countries with prices closer to the OECD median. We examined the impact on the list prices for patented medicines had the amendment been implemented from 2013.Methods: Using IQVIA MIDAS® quarterly sales data, we selected branded products that were launched in Canada in 2013–2018. The list price for each product in each country was calculated as its average annual price during the 3rd year post Canadian launch. The median international price (MIP) was the median of the list prices of PMPRB7 (MIP7) and PMPRB11 (MIP11). We assumed the same IRP would be (scenario 1) or would not be used (scenario 2).Results: Among the selected 400 products, 80.3 % (321) had MIP7 and MIP11 (launched in at least one reference country); 18.3 % did not have MIP11. The total current expenditures were $7,134.4 M. In scenario 1, MIP11 would not be binding for most products and expenditures would decline only by 0.7 %. If IRP were abolished, expenditures might decline by 14.1 % if the launching sequence would not change.Conclusions: MIP11 might not be binding for most medicines. The impact depends on whether to retain the IRP and approaches taken for medicines without MIP11.

Resignations at Canada's drug pricing panel raise independence questions.

A member of Canada’s drug pricing regulator has resigned, stating the federal government has undermined the independence and credibility of the organization. Dalhousie University health law expert Matthew Herder’s resignation from the Patented Medicine Prices Review Board (PMPRB) comes after

Expensive Drugs for Rare Diseases: "Canada, We Have a Problem Here".

This issue of Healthcare Papers on expensive drugs for rare diseases (EDRDs) is very timely. According to the recently released Patented Medicine Prices Review Board's 2021 annual report, EDRDs have gone from 1.7% of pharmaceutical expenditures in 2012 to 12.2% in 2021, with a compound annual growth rate between 2012 and 2021 of 31.7% compared to 6.0% for all prescription medicines (PMPRB 2022).

Reforms to the patented medicine prices review board and the introduction of new drugs in Canada: An observational study

BackgroundInnovative Medicines Canada has said that companies are delaying the introduction of new drugs into Canada in anticipation of changes in how the Patented Medicine Prices Review Board determines prices for patented medicine. This study investigates whether this claim is accurate. MethodsDelays in seeking approval for and marketing of new drugs were examined using linear regression analysis and comparing the time between approvals by Health Canada and approvals of the same drugs by the United States (US) Food and Drug Administration (FDA). Linear regression was also used to examine changes in the percent of drugs approved by the FDA and also approved by Health Canada and whether fewer drugs approved by Health Canada were being marketed. Approvals in Australia served as a control. ResultsThere was no change in the difference in approval times between Health Canada and the FDA (p = 0.7073). Time between approval of new drugs and when they were marketed increased (p = 0.0002). Health Canada approved a smaller percent of drugs approved by the FDA (p = 0.0019) but the same trend was found in Australia. Fewer drugs approved in Canada were marketed (p = 0.0288). ConclusionThere is mixed evidence about whether drug companies are delaying or simply not introducing new drugs into Canada.

Medicines pricing and reimbursement in Canada

Objective: overview of Canadian practices for regulating, financing, and funding prescription drugs. Canada provides universal health coverage for hospital and physician services but excludes universal insurance of prescription medicines. Public plans provide 42% of financing, while private drug insurance covers 35% of expenditures and over 60% of Canadians – mainly through their employer. Canada has relatively high out-of-pocket expenditure (19% of spending) and is currently the tenth largest pharmaceutical market, following Brazil. It is wrestling with inequitable coverage, low use of biosimilars, and affordability and sustainability issues driven by rare disease drugs. Both federal and provincial/territorial governments and their agencies have roles in setting policy and regulating drug prices and costs. These include the federal Patented Medicine Prices Review Board (PMPRB) which ensures prices of new patented drugs are not excessive; the pan-Canadian Pharmaceutical Alliance (pCPA) which negotiates lower patented, generic and biosimilar drug prices on behalf of member jurisdictions; and the Canadian Agency for Drugs and Technologies in Health (CADTH) which provides most public drug plans with robust health technology assessment (HTA), including clinical, economic and budget impact analyses of new drugs. Private drug insurers tend to follow government initiatives, including the use of HTA and confidential Product Listing Agreements. Conclusions: Pharmaceutical coverage in Canada is a “patchwork” of more than 100 public drug plans and 100,000 private insurance plans. As such, it creates gaps in coverage which result in inequitable access and high out-of-pocket drug expenses for some Canadians. Canada’s decentralized health system and the absence of universal drug insurance, among other factors, likely contribute to higher per capita drug expenditure relative to comparable nations that have broader, publicly-funded universal health insurance and more rigourous policy and program strategies.

The Pathway for New Cancer Drug Access in Canada.

Cancer treatment has evolved significantly over the past decade with the emergence of a multitude of new treatments across cancer types. Alongside the pace of drug discovery, the cost of cancer drugs has also increased. In the face of this growth in development and spending, it is crucial to have an understanding of the processes and pressures new drugs navigate to get to the market in Canada. This paper is a review of the complex, multi-step regulatory and funding process undertaken by cancer drugs in Canada. It reviews the role of Health Canada, the Patented Medicine Prices Review Board, the Health Technology Assessment, the pan-Canadian Pharmaceutical Alliance, and finally, the provincial, territorial, and federal payers. Recent developments are highlighted. Strategies to minimize duplication of effort, improve timeliness, and increase efficiency are explored. The cancer drug regulatory and funding process in Canada is complex, and an understanding of the current system and ongoing evolution is essential.

PNS64 Canadian Pricing and Reimbursement: Understanding the Biggest Hurdles in the Payer Landscape

The Canadian national Health Technology Assessment (HTA) is the Canadian Agency for Drugs and Technologies in Health (CADTH) which evaluates the clinical and economic benefits of new therapies to make public reimbursement recommendations (except Quebec). In addition, the Patented Medicine Prices Review Board (PMPRB) has, since 1980, set a national ceiling price for new therapies based on their assessment of their relative therapeutic benefit, their international price and/or domestic therapeutic class price. In 2010, provincial governments established the pan-Canadian Pharmaceutical Alliance (pCPA) to collectively negotiate rebates off the list price for public plans. This research aims to evaluate which of these steps (PMPRB/CADTH/pCPA) is the most challenging for new therapies to overcome. All publicly-available CADTH, PMPRB and pCPA patented drug reports were identified and key data extracted (to 04-JAN-2020). 751 PMPRB outcomes were identified (from 01-JAN-2010), 85% were “within guidance”, 6.8% “does not trigger an investigation”, 2.8% “subject to investigation”, and only 4.8% subject to a “VCU” (Voluntary Compliance Undertaking). 379 completed CADTH appraisals were identified (from 01-JAN-2010), 3% were recommended with no restriction/conditions, 69% recommended with restrictions/conditions, and 28% not recommended. 526 pCPA negotiation outcomes were identified, 65% were concluded with agreement, 10% were concluded without agreement, in 15% negotiations were not pursued, and 10% were ongoing/under consideration. Currently, the substantial hurdles to clear for new therapies in Canada are the CADTH assessment and the pCPA negotiations based upon this assessment. To date, the PMPRB has rarely (<5% cases) issued VCUs to regulate drug prices. However, significant PMPRB reforms are due to be implemented from 01-JUL-2021, including changing the reference basket of countries and allowing their consideration of economic impact, which will significantly increase the number of drugs and magnitude of effect on drug prices.

PDG5 Changes in Canadian Guidelines for Conducting Budget IMPACT Analysis

While the Patented Medicine Prices Review Board (PMPRB) 2007 Budget Impact Analysis (BIA) Guidelines were once considered to be a primary resource for the preparation of pharmaceutical BIAs, they no longer reflect current best practices. Recently, a thorough review and revision of the BIA Guidelines was undertaken by PMPRB staff to more closely align them with the current Canadian requirements and international approaches. With the new Guidelines and a streamlined Excel model template released this year, this presentation will outline the major changes and explain the reasoning behind the updates.

PDG33 Awareness and Consideration of Confidential Listing Agreements in Cost-Effectiveness Evaluation By Health Technology Assessment (HTA) Bodies

Use of confidential listing agreements is growing in Québec (Canada). This reality creates an additional challenge during medicine cost-effectiveness assessment by HTA bodies. The objectives are to briefly describe the nature of listing agreements and identify if other HTA organizations around the world are aware of such agreements and how they take it into consideration. A literature review was conducted to assess the nature of confidential negotiated agreements. Then, HTA bodies’ websites were consulted. HTA organizations were selected if their respective jurisdiction was deemed similar to the ‘consumer protection priorities and economic wealth' of Canada (previously identified by the Patented Medicine Prices Review Board, PMPRB). Additionally, a short questionnaire was sent to members of the International Network of Agencies for Health Technology Assessment (INAHTA) regarding confidential agreements. Discount rate agreements, average ranging from 20 to 29%, are the most common form of listing agreement reported in the literature. Eighteen countries or provinces were included in the analysis (either via the PMPRB criterion or via an answer to the INAHTA questionnaire). Two did not have confidential listing agreements. Eight of the remaining 16 HTA organizations (50%) were aware of the content of the agreement and redacted information in their public reporting of cost-effectiveness analysis. For the 8 organizations that didn't have access to the content, including INESSS, different strategies have been adopted to deal with this uncertainty. While some don't take it into consideration at all, most use sensitivity analysis or, based on an average discount, estimate a discounted price. Access to confidential listing agreements by HTA bodies would be ideal to increase the accuracy of cost-effectiveness analysis and optimize the interpretation of results by decision makers. If impossible, HTA organizations should explore different approaches to illustrate the impact of confidential agreements.

PNS73 THE RIPPLE EFFECT – HOW PMPRB REFORMS COULD IMPACT DRUG PRICES GLOBALLY

The Patented Medicine Prices Review Board (PMPRB) was created in 1987 as an independent quasi-judicial tribunal with a statutory mandate to ensure that the prices of patented medicines in Canada are not excessive. In August 2019, the most significant PMPRB reforms since its inception were announced to come into force in July 2020. These include removing Switzerland and the US from the reference price basket, requiring companies to disclose net prices, and consideration of economic impact to the health system. This research evaluates the impact of the PMPRB to date, to inform a discussion on the effect of these reforms. Patented medicines reported to the PMPRB were screened from their website (01/01/2007-31/12/2017) and key data extracted. 998 reports were identified, a mean of 91/year (range: 65[2007]-128[2016]). 89% (889/998) were deemed “within guidance,” 5% (53/998) as “does not trigger investigation,” 4% (41/998) subject to a Voluntary Compliance Undertaking (VCU, written commitments to comply with PMPRB’s Guidelines, including price adjustments), and the remainder (13/998, 1%) were subject to investigation or under review. The proportion of reports issued that were VCUs has ranged from 2.0% (2/99) in 2014 to 10.3% (7/68) in 2017. Over the last 10 years, the PMPRB have been investigating a greater number of drugs and are increasingly issuing VCUs to regulate drug prices (applying to over a tenth of drugs reviewed in 2017). The PMPRB reforms will significantly increase the number of drugs subject to price regulation and the magnitude of this pricing pressure. With proposals by the US government (in December 2019) to allow states to import branded drugs from Canada, this could significantly put downward pricing pressure in the US and have a major impact on global pharmaceutical revenues.

PNS70 US “IMPORT-FROM-CANADA” DRUG LEGISLATION: WILL IT LOWER DRUG COSTS FOR AMERICAN CONSUMERS?

To address high prescription drug costs, the United States (US) has proposed parallel importation of patented drugs from Canada, which are sold at lower costs. The objective of this review is to assess the implications of the proposed US “import-from-Canada” legislation, using both prior Canada-US and European Union (EU) parallel trade examples. A targeted literature review (TLR) was conducted in relevant databases (EMBASE, Medline, Cochrane, PubMED, PAIS Index, and CINAHL) to identify articles relating to Canada-US parallel trade within the last 20 years (supplemented by a hand-search for EU examples). Overall, 489 articles were identified from the primary search related to Canada-US parallel trade of drugs, leading to 13 articles for analysis after title-abstract and full-text reviews. This search was supplemented by 40 articles related to EU parallel trade through hand-searching. The articles were extracted for: countries involved, relevant legislation/policies, and key findings (e.g. net policy benefits/harms, supporting evidence, etc.) using SWOT framework for analysis. It is important to note that most literature (62%) on this topic was based on opinions versus qualitative or quantitative evidence. Few articles (n=4) reported hypothesized benefits of parallel trade. Claimed benefits included: lowered drug costs, rise in virtual pharmacies, and diminished price-differentiated markets. However, several articles (n=9) identified negative factors, such as: unsustainability of reduced drug prices, threat in profitability of US pharmaceutical companies, arbitragers gaining profit (i.e. insignificant consumer savings), limited drug supply, and increased counterfeit drugs. This is reflective of outcomes observed in the EU, where parallel trade resulted in high profits for arbitragers and drug shortages in source countries. Parallel trade from Canada is unlikely to result in lowered drug costs to American consumers. As Canada implements new dramatic drug price controls (i.e. Patented Medicine Prices Review Board [PMPRB]), manufacturer response to the US legislation may be exacerbated.

Stakeholders' feedback on the proposed recommendations for updating the patented medicine prices review board (pmprb) budget impact analysis guidelines.

The present study aimed to obtain Canadian stakeholders' feedback on a list of proposed recommendations for updating the Patented Medicine Prices Review Board (PMPRB)'s 2007 budget impact analysis (BIA) guidelines. A mixed-methods study was designed to obtain feedback from two stakeholder perspectives-(public and private) payers and manufacturers-on the proposed BIA recommendations. We obtained policymakers' opinion through one-on-one interviews and collected feedback from manufacturers and their consultants using a survey. The interview guide and the survey were developed based on the list of recommendations related to BIA key elements, which were either not discussed or addressed differently in the PMPRB 2007 BIA guidelines. The list was derived from 16 Canadian or other national and transnational BIA guidelines. A thematic analysis was applied for analysis of the qualitative (interview) data. Thirty-five policymakers and manufacturers participated in the study. Stakeholders supported the inclusion of 56% of the proposed recommendations into the guidelines pertaining to the use of expert opinions, data extrapolated from the payers' database, scenario analysis, and dynamic population. Inclusion of indirect costs, and cost transfers from other jurisdictions, were not approved. There was no consensus regarding the inclusion of patients' adherence/compliance and cost offsets. The present study has provided sufficient insights to enable the creation of a penultimate version for updating the PMPRB BIA guidelines. This penultimate version will be subject to a broader consultation among stakeholders prior to a final revision and approval. Further Canadian stakeholder feedback is required for reaching consensus on inconclusive recommendations.

HHS Proposes Plan to Import Lower-Cost Drugs

HHS Proposes Plan to Import Lower-Cost Drugs

A Comparison of Pharmaceutical Budget Impact Analysis (BIA) Recommendations Amongst the Canadian Patented Medicine Prices Review Board (PMPRB), Public and Private Payers.

The Canadian budget impact analysis (BIA) guidelines were published by the Patented Medicine Prices Review Board (PMPRB) in 2007. Some Canadian federal, provincial and territorial (F/P/T) drug plans have updated their BIA guidelines since then. The aim of the present review was to provide a comprehensive list of the key BIA recommendations from the various Canadian F/P/T drug plans and private payers and to highlight the differences between those guidelines and the recommendations that were in the Canadian PMPRB 2007 BIA guidelines. We searched the websites of fifteen F/P/T public drug benefit programs including the Canadian Agency for Drugs and Technologies in Health (CADTH) and Non-Insured Health Benefits Program (NIHBP) and five private payers’ websites. An Excel-based data abstraction form was designed to highlight differences between recommendations relating to the BIA key elements made by different guidelines. Eight BIA guidelines (PMPRB 2007, Alberta, British Columbia, Manitoba, Ontario, Quebec, CADTH, and Medavie Blue Cross) were identified and reviewed, and a comprehensive list of recommendations was abstracted. Recommendations were similar to the 2007 guidelines in terms of time horizon duration, comparators, target population assessment and use of direct drug costs in BIAs. Differences were mostly related to actual acquisition cost, such as whether or not to include markups and dispensing fees, the patients’ perspective, cost of supplies, cost of health care utilization, and scenario analysis. The recommendations that were not included in the PMPRB 2007 guidelines but were included in at least one of the Canadian F/P/T or private guidelines were related to the inclusion of the patients’ perspective (i.e., co-payment), the costing, the handling of uncertainty and the reporting format. The present study is a comparative review of recommendations between the Canadian PMPRB 2007 guidelines and the F/P/T or private payers’ BIA guidelines, and provides a most up-to-date list of recommendations for revising the Canadian BIA guidelines, with applicability for both public and private plan new drug submissions in Canada.

Health Canada’s use of expedited review pathways and therapeutic innovation, 1995–2016: cross-sectional analysis

ObjectivesThis study examines the use of expedited approval pathways by Health Canada over the period 1995 to 2016 inclusive and the relationship between the use of these pathways and the...

Canadian status of "drugs to avoid" in 2017: a descriptive analysis.

The independent French drug bulletin, La revue Prescrire (henceforth Prescrire), annually releases a list of drugs to avoid. The aim of this analysis was to review the status of the 2017 list of drugs in Canada to determine whether they had been approved for marketing, their therapeutic status and whether they have been recommended for listing on public drug plans. This descriptive analysis reviewed a list of drugs compiled by Prescrire. The status of each drug in Canada was assessed through the Drug Product Database. Therapeutic ratings were obtained from the Patented Medicine Prices Review Board (PMPRB) and the formulary listing recommendation came from the Common Drug Review (CDR) or the pan-Canadian Oncology Drug Review (pCODR). For drugs without a formulary recommendation the Ontario Drug Benefit (ODB) Formulary was searched to see if the product was listed. Prescrire recommended not using 92 drugs. The PMPRB evaluated 36 of these drugs; 2 were classed as substantial improvements or breakthroughs, 3 as moderate improvements and 31 as little or no therapeutic improvement. Nine of the remaining drugs that were approved in Canada were not assessed because they were approved before 1988 (the year the PMPRB was established), 4 were approved from December 2015 onward and had not yet been reviewed by the PMPRB, and for 1 the approval date was unknown. Twenty-six of the drugs were evaluated by CDR or pCODR, of which 13 were recommended for formulary listing. Sixteen additional drugs that were not evaluated were on the ODB Formulary. Many drugs that Prescrire recommended avoiding were available in Canada. The results also highlight the diversity of the conclusions that different expert panels have reached.

PHP132 - Potential Impact of Changes to Basket of Comparator Countries from PMPRB7 to Pmprb12 has on Canadian Product List Prices

To predict/estimate the potential impact on maximum prices for patented medicines in Canada after new Patented Medicine Prices Review Board (PMPRB) regulations, to update comparator countries from PMPRB7 to PMPRB12, are implemented. The study sample consists of 16% of the patented drug products reported to PMPRB, in 2016. For each product, the most common Canadian list price (in most cases the highest Canadian list price), not the average transaction price, was compared to international prices in PMPRB7 and PMPRB12. The following tests were conducted to determine the proportion of products with a Canadian list price that was higher than the international comparator metric and the associated maximum/minimum price reductions (MxPR/MnPR, respectively) required to match the international comparator metric: Highest International Price Comparison (HIPC) and Median International Price Comparison (MIPC). Data Sources: international public formularies for PMPRB7 countries and Australia; IMS Pricing Insights (as of June 2017) for the other 5 countries in PMPRB12. The Canadian list prices of 42% of the study sample were found to be higher than HIPC for PMPRB12 (MxPR 96%, MnPR 0.2%); 1% was higher for PMPRB7 (MxPR 25%, MnPR 11%). MIPC test: 70% of the sample was higher for PMPRB12 (MxPR 76%, MnPR 6%); 49% was higher for PMPRB7 (MxPR 76%, MnPR 1%). If implemented, the federally mandated change to the basket of comparator countries is expected to have a significant impact on patented drug pricing and will require a significant proportion of drugs to decrease their prices, with just the change in basket countries. If a median international price ceiling is applied to existing drugs, the impact can be expected to affect the majority of drugs with list price reductions of at least 6%. Draft PMPRB Guidelines (Spring 2018) will provide direction on how any changes will affect existing drugs.

Pharmaceutical company spending on research and development and promotion in Canada, 2013-2016: a cohort analysis

BackgroundCompeting claims are made about the amount of money that pharmaceutical companies spend on research and development (R&D) versus promotion. This study investigates this question in the Canadian context.MethodsTwo methods for determining industry-wide figures for spending on promotion were employed. First, total industry spending on detailing and journal advertising for 2013-2016 was abstracted from reports from QuintilesIMS. Second, the mean total promotion spending for the years 2002-2005 was used to estimate total spending for 2013-2016. Total industry spending on R&D came from the Patented Medicine Prices Review Board (PMPRB). R&D to promotion spending using each method of determining the amount spent on promotion was compared for 2013-2016 inclusive. Data on the 50 top promoted drugs, the amounts spent, the companies marketing these products and their overall sales were abstracted from the QuintilesIMS reports. Spending on R&D and promotion as a percent of sales was compared for these companies.ResultsIndustry wide, the ratio of R&D to promotion spending went from 1.43 to 2.18 when promotion was defined as the amount spent on detailing and journal advertising for the 50 most promoted drugs. Calculating total promotion spending from the mean of the 2002-2005 figures the ratio was 0.88 to 1.32 for the 50 most promoted drugs. For individual companies marketing one or more of the 50 most promoted drugs, mean R&D spending ranged from 3.7% of sales to 4.1% compared to mean promotion spending that went from 1.7 to 1.9%. The ratio of spending on R&D to promotion varied from 2.11 to 2.32. Eight to 10 companies per year spent more on promotion than on R&D.ConclusionsDepending on the method used to determine promotion spending, industry-wide the ratio of R&D spending to promotion ranges from 1.45 to 2.18 (sales representatives and journal advertising only) or from 0.88 to 1.32 (total promotion spending estimated based 2003-2005 data.) For the individual companies promoting one or more of the 50 most promoted drugs, 2.11 to 2.32 times more is spent on R&D compared to promotion. However these results should be interpreted cautiously because of data limitations.

PP51 Updating Canadian Pharmaceutical Budget Impact Analysis Guidelines

Introduction:The Canadian BIA guideline was published by the Patented Medicine Prices Review Board (PMPRB) in 2007. Our initial systematic literature review of national and international BIA guidelines showed that a number of new recommendations relating to BIA model structure, input data and reporting format have been adopted in other jurisdictions such as UK, Australia, Poland, Ireland, Belgium, France and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). The main objective of the present study was to conduct a comparative review of national, international and Canadian Federal, provincial and territorial BIA guidelines and provide a list of new recommendations related to the BIA key elements which have not been discussed or included in the Canadian PMPRB BIA guidelines.Methods:BIAs guidelines were searched in databases such as MEDLINE, EMBASE, Cochrane, and the gray literature including regulatory agency websites. An Excel-based data abstraction form was designed in order to highlight differences between recommendations related to the BIA key elements provided by PMPRB, provincial, and other national and international BIA guidelines.Results:Twelve guidelines were reviewed in detail. Sixty percent of the recommendations were new or were different from recommendations in the Canadian PMPRB BIA guidelines. They related to BIA key elements such as perspective, target population, costing, presenting results, data sources and handling the uncertainty.Conclusions:The present literature review is the initial step towards updating the Canadian BIA guidelines. This study presents a comparative review of key elements in BIA among different guidelines and provides a list of relevant practical recommendations for the improvement of the Canadian BIA guidelines. The new methodologic advancements and recommendations that were identified are being presented to Canadian stakeholders for their opinion and feedback prior to the development of a proposed new set of Canadian guidelines.