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The interest of the pharmaceutical industry is in achieving a profit for its shareholders while the interest of the Canadian government should be in protecting public health. However, over the course of the past few decades the actions of the Canadian government have been tilted in favour of industry in two areas. The first is in the relationship between industry and Health Canada and is manifested in the regulation of clinical trials, the drug approval system, drug safety and promotion. The second is in economic policy as it applies to policies about patent protection, the price of medications and measures taken to incentivize research and development. The problems in the relationship are structural and will only be solved through systemic changes., (Copyright © 2017 Longwoods Publishing.)

Competing Interests: Competing interests: In 2015/16, Joel Lexchin received payment from two nonprofit organizations as a consultant on one project that dealt with indication-based prescribing, and a second on which drugs should be distributed free of charge by general practitioners. In 2015, he received payment from a for-profit organization for participation on a panel that discussed expanding drug insurance in Canada. He is on the Foundation Board of Health Action International.

Background: Clinical research affecting how doctors practice medicine is increasingly sponsored by companies that make drugs and medical devices. Previous systematic reviews have found that pharmaceutical-industry sponsored studies are more often favorable to the sponsor's product compared with studies with other sources of sponsorship. A similar association between sponsorship and outcomes have been found for device studies, but the body of evidence is not as strong as for sponsorship of drug studies. This review is an update of a previous Cochrane review and includes empirical studies on the association between sponsorship and research outcome., Objectives: To investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship., Search Methods: In this update we searched MEDLINE (2010 to February 2015), Embase (2010 to February 2015), the Cochrane Methodology Register (2015, Issue 2) and Web of Science (June 2015). In addition, we searched reference lists of included papers, previous systematic reviews and author files., Selection Criteria: Cross-sectional studies, cohort studies, systematic reviews and meta-analyses that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. We had no language restrictions., Data Collection and Analysis: Two assessors screened abstracts and identified and included relevant papers. Two assessors extracted data, and we contacted authors of included papers for additional unpublished data. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether the conclusions agreed with the study results. Two assessors assessed risk of bias of included papers. We calculated pooled risk ratios (RR) for dichotomous data (with 95% confidence intervals (CIs))., Main Results: Twenty-seven new papers were included in this update and in total the review contains 75 included papers. Industry sponsored studies more often had favorable efficacy results, RR: 1.27 (95% CI: 1.17 to 1.37) (25 papers) (moderate quality evidence), similar harms results RR: 1.37 (95% CI: 0.64 to 2.93) (four papers) (very low quality evidence) and more often favorable conclusions RR: 1.34 (95% CI: 1.19 to 1.51) (29 papers) (low quality evidence) compared with non-industry sponsored studies. Nineteen papers reported on sponsorship and efficacy effect size, but could not be pooled due to differences in their reporting of data and the results were heterogeneous. We did not find a difference between drug and device studies in the association between sponsorship and conclusions (test for interaction, P = 0.98) (four papers). Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment, follow-up and selective outcome reporting. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.25 (95% CI: 1.05 to 1.50) (13 papers), compared with non-industry sponsored studies. In industry sponsored studies, there was less agreement between the results and the conclusions than in non-industry sponsored studies, RR: 0.83 (95% CI: 0.70 to 0.98) (six papers)., Authors' Conclusions: Sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.

Canada is the only country with a universal public health care system that does not include coverage for prescription drugs; lack of drug coverage leads to underuse of necessary medications. Arguments have been advanced for and against a national pharmacare plan. This article investigates six commonly cited reasons for not introducing such a program in order to determine their validity - private plans are doing a good job, public plans should only cover the poor, strengthening the pan-Canadian Pharmaceutical Alliance is all that is needed, a public plan will deny people access to important new drugs, pharmacare will cost too much and pharmacare is just about money. The evidence presented shows that these are just myths.

Background: Professional medical associations (PMAs) play a crucial role in providing accredited continuing medical education (CME) to physicians. Funding from the pharmaceutical industry may lead to biases in CME., Objective: This study examines publicly available policies on CME, adopted by Canadian PMAs as of December 2015., Methods: Policies were evaluated using an original scoring tool comprising 21 items, two questions about PMAs' general and CME funding from industry, and three enforcement measures., Results: We assessed 236 policies adopted by Canadian PMAs (range, 0 to 32). Medical associations received summative scores that ranged from 0% to 49.2% of the total possible points (maximum score = 63). Twenty-seven associations received an overall score of 0%. The highest mean scores were achieved in the areas of industry involvement in planning CME activities (mean: 1.1/3), presence of a review process for topics of CME activities (mean: 1.1/3), content review for balanced information (mean: 1.1/3), and responsibility of distribution of funds (mean: 1.0/3). The lowest mean scores were achieved in the areas of awards (mean: 0.0/3), industry personnel, representatives, and employees (mean: 0.1/3), distribution of industry-funded educational materials at CME activities (mean: 0.1/3), and distinction between marketing and educational materials (mean: 0.1/3)., Conclusion: These results suggest that Canadian PMAs' publicly available policies on industry involvement in CME are generally weak or non-existent; therefore, the accredited CME that is provided to Canadian physicians may be viewed as open to bias. We encourage all Canadian medical associations to strengthen their policies to avoid the potential for industry influence in CME.

Diverse legal and regulatory measures are used internationally to control the information provided during pharmaceutical sales visits. Little is known about the comparative effectiveness of these measures however. We analyzed the perceptions of regulators, pharmaceutical industry officials, health professionals, and consumer respondents concerning these approaches in Canada, France, and the United States using an empirical realist interests-based approach. Interviews focused on the aims and effectiveness of regulation, barriers and enablers to regulation and suggestions for improvement. An alignment was found in North America regulator and industry respondents' satisfaction with the status quo and their view that further intervention is unfeasible and unnecessary. Health professionals generally expressed a lack of confidence in the impact of regulations on sales visit information while consumer advocates voiced their disappointment in both regulators and health professionals for their failure to counteract the influence of pharmaceutical marketing. Regulator and industry respondents in France differed from their North American counterparts in their willingness to increase and diversify the scope of regulatory interventions. As the first international comparison of regulatory experiences in this sector, the findings highlight the universal need for more focused and inclusive discussions among groups about how to tailor regulations to achieve public health goals.

Introduction: First-in-class drugs use a unique mechanism of action. This study assessed the therapeutic innovativeness and safety of these drugs approved by Health Canada from 1997-2012., Methods: A list of new drugs was compiled and a database from the Food and Drug Administration was used to determine first-in-class status. Post-market safety warnings and drugs withdrawn for safety reasons were identified from the MedEffect Canada website. Therapeutic innovation evaluations came from the Patented Medicine Prices Review Board (PMPRB) and Prescrire International. The proportion of first-in-class drugs that were innovative was compared to the proportion of non-first-in-class drugs that were innovative. Kaplan-Meier survival curves assessed safety., Results: In all, 462 drugs were approved by Health Canada during the period under study. Among these, 345 were evaluated by PMPRB and/or Prescrire, and first-in-class data were available for 292. Ninety-eight of the 292 were first-in-class and 16 were innovative compared to 9 of 194 drugs that were not-first-in-class. There was no difference in safety between the two groups., Discussion: Overall, the benefit-to-harm ratio of first-in-class drugs, as measured by post-market safety warnings/withdrawals, is better than those that were not-first-in-class., (Copyright © 2016 Longwoods Publishing.)

The Trans Pacific Partnership Agreement (TPP) is a large regional trade agreement involving 12 countries. It was signed in principle in February 2016 but has not yet been ratified in any of the participating countries. The TPP provisions place a range of constraints on how governments regulate the pharmaceutical sector and set prices for medicines. This article presents a prospective policy analysis of the possible effects of the TPP on these two points in Canada and Australia. Five chapters of relevance to pharmaceutical policy are analyzed: chapters on Technical Barriers to Trade (Chapter 8), Intellectual Property (Chapter 18), Investment (Chapter 9), Dispute Resolution (Chapter 28), and an annex of the chapter on Transparency and Anti-Corruption (Chapter 26, Annex 26-A). The article concludes that the TPP could have profound effects on the criteria these countries use to decide on drug safety and effectiveness, how new drugs are approved (or not) for marketing, post-market surveillance and inspection, the listing of drugs on public formularies, and how individual drugs are priced in the future. Furthermore, the TPP, if ratified and enforced, will reduce future policy flexibility to address the increasing challenge of rising drug prices., (© The Author(s) 2016.)

Background: Clinical practice guidelines are widely distributed by medical associations and relied upon by physicians for the best available clinical evidence. International findings report that financial conflicts of interest (FCOI) with drug companies may influence drug recommendations and are common among guideline authors. There is no comparable study on exclusively Canadian guidelines; therefore, we provide a case study of authors' FCOI declarations in guidelines from the Canadian Medical Association (CMA) Infobase. We also assess the financial relationships between guideline-affiliated organizations and drug companies., Methods: Using a population approach, we extracted first-line drug recommendations and authors' FCOI disclosures in guidelines from the CMA Infobase. We contacted the corresponding authors on guidelines when FCOI disclosures were missing for some or all authors. We also extracted guideline-affiliated organizations and searched each of their websites to determine if they had financial relationships with drug companies., Results: We analyzed 350 authors from 28 guidelines. Authors were named on one, two, or three guidelines, yielding 400 FCOI statements. In 75.0 % of guidelines at least one author, and in 21.4 % of guidelines all authors, disclosed FCOI with drug companies. In 54.0 % of guidelines at least one author, and in 28.6 % of guidelines over half of the authors, disclosed FCOI with manufacturers of drugs that they recommended. Twenty of 48 authors on multiple guidelines reported different FCOI in their disclosures. Eight guidelines identified affiliated organizations with financial relationships with manufacturers of drugs recommended in those guidelines., Conclusions: This is the first study to systematically describe FCOI disclosures by authors of Canadian guidelines and financial relationships between guideline-affiliated organizations and pharmaceutical companies. These financial relationships are common. Because authoritative value is assigned to guidelines distributed by medical associations, we encourage them to develop formal policies to limit the potential influence of FCOI on guideline recommendations.

Canada needs a national strategy to fulfill its obligation to ensure universal access to necessary healthcare, including prescription drugs. A 2004 attempt at a national strategy for pharmaceutical policy failed because it lacked clear vision, logical planning and commitment from federal and provincial governments. The result of uncoordinated pharmaceutical policies in Canada has been more than a decade of poor system performance. In this essay, we present a framework for a renewed national strategy for pharmaceutical policy. Building on published research and international frameworks, we propose that pharmaceutical policies of federal, provincial and territorial governments be coordinated around a core health-focused goal. We strongly suggest policy actions be taken on four core objectives that are necessary to support the overarching health goal. If implemented, the proposed strategy would offer clear benefits to all Canadians who use medicines, federal and provincial governments and to the economy as a whole. We therefore argue that political leadership is now needed to articulate and implement such a plan on behalf of Canadians., (Copyright © 2016 Longwoods Publishing.)

Margaret McGregor and colleagues consider Bradford Hill's framework for examining causation in observational research for the association between nursing home care quality and for-profit ownership.

Aims: Adverse drug events are an important cause of emergency department visits, unplanned admissions and prolonged hospital stays. Our objective was to synthesize the evidence on the effect of early in-hospital pharmacist-led medication review on patient-oriented outcomes based on observed data., Methods: We systematically searched eight bibliographic reference databases, electronic grey literature, medical journals, conference proceedings, trial registries and bibliographies of relevant papers. We included studies that employed random or quasi-random methods to allocate subjects to pharmacist-led medication review or control. Medication review had to include, at a minimum, obtaining a best possible medication history and reviewing medications for appropriateness and adverse drug events. The intervention had to be initiated within 24 h of emergency department presentation or 72 h of admission. We extracted data in duplicate and pooled outcomes from clinically homogeneous studies of the same design using random effects meta-analysis., Results: We retrieved 4549 titles of which seven were included, reporting the outcomes of 3292 patients. We pooled data from studies of the same design, and found no significant differences in length of hospital admission (weighted mean difference [WMD] -0.04 days, 95% confidence interval [CI] -1.63, 1.55), mortality (odds ratio [OR] 1.09, 95% CI 0.69, 1.72), readmissions (OR 1.15, 95% CI 0.81, 1.63) or emergency department revisits at 3 months (OR 0.60, 95% CI 0.27, 1.32). Two large studies reporting reductions in readmissions could not be included in our pooled estimates due to differences in study design., Conclusions: Wide confidence intervals suggest that additional research is likely to influence the effect size estimates and clarify the effect of medication review on patient-oriented outcomes. This systematic review failed to identify an effect of pharmacist-led medication review on health outcomes., (© 2015 The British Pharmacological Society.)

The benefits and harms of antipsychotic medication (APM) use in nursing home residents need to be examined because, although commonly used, APMs are considered an off-label use by the Food and Drug Administration for residents with dementia and behavioral problems. The objective of this study was to provide a realist literature review, summarizing original research studies on the clinical effects of conventional and atypical APM use in nursing home residents. Searches of multiple databases identified 424 potentially relevant research articles, of which 25 met the inclusion criteria. Antipsychotic medication use in nursing home residents was found to have variable efficacy when used off-label with an increased risk of many adverse events, including mortality, hip fractures, thrombotic events, cardiovascular events and hospitalizations. Findings suggested certain APM dosing regimens (e.g. fixed-dose) and shorter duration of use might have fewer adverse events. Non-pharmacological interventions should still be considered the first-line treatment option for nursing home residents with dementia related behavioral disturbances, as more studies are needed to establish safer criteria for APM use in nursing homes residents., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aims: Health Canada has developed a pathway to approve drugs that have limited efficacy and safety data, the Notice of Compliance with conditions (NOC/c) policy. Increased safety reporting is required for these drugs but there has not been any systematic review of their post-market safety. This study compares safety warnings for NOC/c drugs with drugs with a priority and a standard review., Methods: A list of drugs approved between January 1 1998 and March 31 2013 was developed and serious safety warnings for these drugs were identified. Drugs were put into one of three groups based on the way that they were approved. Kaplan-Meier curves were generated to examine the likelihood of NOC/c drugs receiving a serious safety warning compared with drugs with a priority and a standard review. The time spent in the review process for each of the groups was also measured., Results: Compared with drugs with a priority review, NOC/c drugs were not more likely to receive a serious safety warning (P = 0.5940) but were more likely than drugs with a standard review (P = 0.0113). NOC/c drugs spent less time in the review process compared with drugs with a standard review., Conclusions: Possible reasons for the increase likelihood of a serious safety warning are the limited knowledge of the safety of NOC/c drugs when they are approved and the length of time that they spend in the review process. Health Canada should consider spending longer reviewing these drugs and monitor their post-market safety more closely., (© 2014 The British Pharmacological Society.)

Some drugs eventually have to be removed from the market because of a negative benefit-to-harm ratio, including an excess of mortality. Drug safety is the result of multiple factors, commencing with how clinical trials are designed, the information generated by and/or hidden through these trials, trial analysis by drug regulatory authorities (DRAs) and the amount of information that DRAs choose to release, the amount of published information regarding drug safety, the effectiveness of postmarket surveillance systems in recognizing and reporting adverse drug reactions, and the structure of DRAs such as the United States Food and Drug Administration and its equivalent in other countries. This commentary will look at each of these issues in order to highlight the problems in the current approach to drug safety and finally indicate how some of these deficiencies should be addressed.

Background: Drugs are approved for formulary listing based on limited knowledge of their safety. Serious safety issues are often identified after a drug is marketed., Objective: To determine whether the listing status of drugs on the Ontario Drug Benefit (ODB) Formulary changes following the identification of safety concerns by Health Canada and whether the results of reviews by people responsible for the ODB Formulary are made public., Methods: All new active substances (NAS) approved by Health Canada from January 1, 2002 to March 31, 2012 that subsequently had a warning issued about a serious safety concern were identified. Editions of the ODB Formulary were searched to find which of these drugs were listed on the Formulary before the safety warning was issued., Results: A total of 263 NAS were approved of which 42 subsequently acquired one or more serious safety warnings and 15 of these were listed on the ODB Formulary before the safety warning was issued. The listing status of 14 of the 15 drugs was unchanged after the release of the safety warning. No information is available about whether the listing status of these 14 drugs was reassessed., Conclusions: The ODB Formulary should develop a set of criteria to determine whether the listing status of drugs should be reviewed after Health Canada issues a serious safety warning. The results of any reconsiderations should made public so that prescribers and patients alike know that the ODB Formulary officials still regard the drugs as having a positive benefit to harm ratio.

Background: Although selective and incomplete publication is widely acknowledged to be a problem, full access to clinical trial data remains illusive., Sources of Data: Authors' personal files, key documents from Food and Drug Administration and European Medicines Agency and focussed searches of PubMed., Areas of Agreement: Existing sources of information provide an incomplete overview of scientific research., Areas of Controversy: Persistent arguments about commercial confidentiality and the potential difficulties in de-identifying raw data can block important progress. Current industry efforts are voluntary and only partially satisfy the need for complete data., Growing Points: Requirements for trial registration are increasing. Important regulatory changes in particular in Europe have the potential to result in the release of more information., Areas Timely for Developing Research: Documenting the effects of prospective trial registration and requirements for proactive clinical trial publication on healthcare decisions, public health and rational resource allocation., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To obtain information about the similarities and differences in regulating different types of medical research in the European Union (EU)., Methods: Web searches were performed from September 2009 to January 2011. Notes on pre-determined topics were systematically taken down from the web pages. The analysis relied only on documents and reports available on the web, reflecting the situation at the end of 2010., Results: In several countries, regulatory legislation applied only to clinical trials on drugs and medical devices, in other states various types of research were also regulated but by laws different from those concerning trials, and in many countries, some research areas were not controlled by legislation at all. In very few countries was all medical research handled similarly from a legal point of view. The number of research ethics committees (RECs) in a single country varied from one to 264. Their areas of responsibility, working principles and length of time to grant research permission varied as well as the rules for obtaining informed consent from vulnerable groups. In 10 EU countries, there was no appeal mechanism after a negative decision by an REC. The RECs were not accountable to any organisation in five EU countries., Conclusions: There is a need for a fundamental debate regarding whether and which kinds of changes are needed for the further harmonisation of medical research governance in the EU and how cross-country medical research could be facilitated in the future., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

On a per capita basis, Canadian drug costs are already the second highest in the world after the United States and are among the fastest rising in the Organization for Economic Co-Operation and Development. The Comprehensive Economic and Trade Agreement (CETA) between the European Union (EU) and Canada will further exacerbate the rise in costs by:  Committing Canada to creating a new system of patent term restoration thereby delaying entry of generic medicines by up to two years; Locking in Canada's current term of data protection, and creating barriers for future governments wanting to reverse it;  Implementing a new right of appeal under the patent linkage system that will create further delays for the entry of generics.CETA will only affect intellectual property rights in Canada-not the EU. This analysis estimates that CETA's provisions will increase Canadian drug costs by between 6.2% and 12.9% starting in 2023. The Canadian government committed to compensating provinces for the rise in costs for their public drug plans. Importantly, this means that people paying out-of-pocket for their drugs or receiving them through private insurance, will be charged twice: once through higher drug costs and once more through their federal taxes.As drug costs continue to grow, there are limited options available for provincial/territorial governments: restrict the choice of medicines in public drug plans; transfer costs to patients who typically are either elderly or sick; or take money from other places in the health system, and threaten the viability of Canada's single payer system. CETA will therefore negatively impact the ability of Canada to offer quality health care.

Background: Health Canada's Summary Basis of Decision (SBD) documents outline the clinical trial information that was considered in approving a new drug. We examined the ability of SBDs to inform clinician decision-making. We asked if SBDs answered three questions that clinicians might have prior to prescribing a new drug: 1) Do the characteristics of patients enrolled in trials match those of patients in their practice? 2) What are the details concerning the drug's risks and benefits? 3) What are the basic characteristics of trials?, Methods: 14 items of clinical trial information were identified from all SBDs published on or before April 2012. Each item received a score of 2 (present), 1 (unclear) or 0 (absent). The unit of analysis was the individual SBD, and an overall SBD score was derived based on the sum of points for each item. Scores were expressed as a percentage of the maximum possible points, and then classified into five descriptive categories based on that score. Additionally, three overall 'component' scores were tallied for each SBD: "patient characteristics", "benefit/risk information" and "basic trial characteristics"., Results: 161 documents, spanning 456 trials, were analyzed. The majority (126/161) were rated as having information sometimes present (score of >33 to 66%). No SBDs had either no information on any item, or 100% of the information. Items in the patient characteristics component scored poorest (mean component score of 40.4%), while items corresponding to basic trial information were most frequently provided (mean component score of 71%)., Conclusion: The significant omissions in the level of clinical trial information in SBDs provide little to aid clinicians in their decision-making. Clinicians' preferred source of information is scientific knowledge, but in Canada, access to such information is limited. Consequently, we believe that clinicians are being denied crucial tools for decision-making.

Objectives: Examine the probability of new active substances (NASs) approved in Canada between 1 January 1997 and 31 March 2012 acquiring a serious postmarket safety warning., Design: Cohort study., Data Sources: Annual reports of the Therapeutic Products Directorate and the Biologic and Genetic Therapies Directorate; evaluations of therapeutic innovation from the Patented Medicine Prices Review Board and Prescrire International; MedEffect Canada website., Interventions: Postmarket regulatory safety warning or withdrawal from market due to safety reasons., Primary and Secondary Outcome Measures: Compare the probability of acquiring a postmarket safety warning in Canada in four different groups of drugs: (1) traditional medications versus biologics; (2) medications that offer significant new therapeutic benefits versus those that do not. Determine how well the type of review that an NAS received from Health Canada predicted the product's postmarket therapeutic value., Results: The probability of a traditional NAS acquiring a serious safety warning and/or being withdrawn was 29.9% (95% CI 21.8% to 40.2%) vs 27.3% (95% CI 18.2% to 39.7%) for an NAS of biological origin (p=0.47, log-rank test). For medications that were significant therapeutic advances the probability was 40.2% (95% CI 24.5% to 60.9%) vs 33.9% (95% CI 26.4% to 42.7%) for those that were not (p=0.18, log-rank test). Health Canada was 77.4% accurate in predicting the therapeutic importance of an NAS., Conclusions: There was no difference in postmarket regulatory safety action between traditional medications and biologics and no difference between drugs with significant therapeutic benefits and those without. Although these results draw on Canadian data, they are likely to be relevant internationally. Further research should assess whether the current level of premarket safety evaluation is acceptable.

Background: Studying drugs withdrawn from the market for safety reasons can help in evaluating the strengths and weaknesses of the pre- and post-market safety evaluation systems. This study considered 2 questions: Has there been a change over time in the percentage of new drugs that are eventually withdrawn because of safety reasons? How long are new drugs on the market before their serious safety problems are recognized?, Methods: All drugs approved between 1 January 1990 and 31 December 2009 and subsequently withdrawn for safety reasons (until 1 October 2013) were identified, and the generic name, date of approval, and date of withdrawal were recorded. The total number of drugs approved over the same period was obtained from annual Health Canada reports. The percentages of new active substances approved in the 5-year periods 1990-1994, 1995-1999, 2000-2004, and 2005-2009 and eventually withdrawn were compared using the χ(2) test. The time between approval and withdrawal was calculated in days., Results: Of the 528 new drugs approved over the period of interest, a total of 22 (4.2%) were eventually withdrawn. Between 3.9% and 4.4% of the drugs approved in each 5-year period were eventually withdrawn (χ(2) = 0.04, p = 0.99 for difference among 5-year periods). The median time between approval and withdrawal was 1271 days (interquartile range 706-2876)., Interpretation: One explanation for the finding of no difference in the percentage of drugs approved in the four 5-year periods that were eventually withdrawn is the lack of any change in the rigour of the premarket evaluation system and the postmarket surveillance systems. The 1271-day median time between Notice of Compliance and withdrawal emphasizes the need to be particularly cautious in prescribing new drugs early in their life cycle.

Background: Pharmaceutical advertisements have been argued to provide revenue that medical journals require but they are intended to alter prescribing behaviour and they are known to include low quality information. We determined whether a difference exists in the current level of pharmaceutical advertising in print general medical journals, and we estimated the revenue generated from print pharmaceutical advertising., Methods: Six print general medical journals in Canada, the United States, and the United Kingdom were sampled between 2007 and 2012. The number of advertisements and other journal content in selected issues of the Canadian Medical Association Journal (CMAJ), Canadian Family Physician (CFP), Journal of the American Medical Association (JAMA), New England Journal of Medicine (NEJM), British Medical Journal (BMJ), and Lancet were determined. Revenue gained from pharmaceutical advertising was estimated using each journal's 2013 advertising price list., Findings: The two Canadian journals sampled (CMAJ, CFP) contained five times more advertisements than the two American journals (JAMA, NEJM), and two British journals (BMJ, Lancet) (p<0.0001). The estimated annual revenue from pharmaceutical advertisements ranged from £0.025 million (for Lancet) to £3.8 million (for JAMA). The cost savings due to revenue from pharmaceutical advertising to each individual subscriber ranged from £0.02 (for Lancet) to £3.56 (for CFP) per issue., Conclusion: The volume of pharmaceutical advertisements differs between general medical journals, with the two Canadian journals sampled containing the most advertisements. International and temporal variations suggest that there is an opportunity for all general medical journals to reduce the number of pharmaceutical advertisements, explore other sources of revenue, and increase transparency regarding sources of revenue.

Background: Since the mid 1990's, Canada has introduced partial direct-to-consumer advertising (DTCA) of prescription drugs through administrative policy shifts. Little documentation exists on how regulation occurs in practice., Objective: To evaluate Health Canada's response to complaints about DTCA., Methods: We use case studies about DTCA spanning from 2000 to 2011 to examine the stringency of regulation by Health Canada. The aim was to identify key themes in Health Canada's approach to regulation from a public health perspective. All of the material related to the cases was independently read by each of the authors and any disagreements in interpretation were resolved through discussion., Results: We identified six weaknesses in how Health Canada deals with DTCA: failure to act on concerns about promotion for unapproved "off-label" uses, possible financial inducements to use a product, advertisements perceived to stimulate unwarranted fear about disease risks, and advertising of products with serious safety concerns identified in Health Canada safety advisories; ineffective enforcement actions undertaken by Health Canada; and lack of transparency in Health Canada's decision-making., Conclusions: There is an astonishing degree of discordance between public health priorities and regulation of DTCA in Canada. The current approach to enforcement is notable both for its lack of teeth and lack of accountability and transparency.

Clinical trials present an ethical dilemma for pharmaceutical companies. While companies may want to undertake and report these trials in an ethical manner, negative results can significantly affect product sales. There is accumulating evidence that company-financed trials are biased in favor of the product that the company makes. Ethical conduct in this article is defined as whether the trials are conducted in the best interests of the participants and/or reported in the best interests of patients. Nine examples of how clinical trials are violating multiple articles in the Declaration of Helsinki are discussed using concrete case reports from the literature. The recognition of ethical problems in company run trials is not something new, but to date no meaningful action has been taken to resolve this issue. What is necessary is to separate the financing of clinical trials from their conduct.

In the past two decades, Health Canada has been accused of favouring the pharmaceutical industry over the public in areas of pharmaceutical policy. This orientation has been tied to the introduction of user fees by the industry in 1994 that help finance key aspects of drug regulation. This paper provides a preliminary examination of the history of the relationship starting in 1939 until the mid-1980s in an attempt to discern whether 1994 really represented a key turning point. Clientele pluralism, a theory that explains the relationship between the state and interest groups, is used to explain the nature of the events described., (Copyright © 2013 Longwoods Publishing.)

Background: Many health professional and regulatory groups have guidelines for identifying, disclosing and managing potential conflicts of interest (COI). The opinions of the Canadian public regarding what constitutes COI are unknown., Methods: Bilingual telephone survey in all provinces using a validated questionnaire on public opinions on physician-pharmaceutical industry interactions (POPPII). Adults 18 years or older were contacted using random digit dialing (RDD) with representative national sampling of households. Results were analyzed for predictors of opinions and were compared with the reference COI guideline. Two follow-up focus groups were held., Results: 1041 participants (56.8% female, mean age 52.6 years (SD 16.5), 18.2% francophone, 57.7% with post-secondary education) completed the survey. 34.0% reported a prior concern about physician-pharmaceutical industry relationships. Acceptability of interactions varied from high for requesting information about a particular drug or small gifts of obvious educational value to the patient, to mixed for free meals to listen to pharmaceutical industry personnel or payment to attend a conference, to low for research recruitment fees, personal use of medication samples or for using information not yet public about a new drug to make investment decisions. Age of the participant influenced ratings of acceptability. There was reasonable agreement (>60% participants) with only half of the related reference COI guideline statements., Conclusions: Public opinions on physician-pharmaceutical industry interactions differ depending on the scenario but suggest a significant level of concern regarding interactions involving direct financial benefit to physicians., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Canadian reports have recommended that health as a human right must be Canada's overarching global commitment and that the primacy of human rights should be prioritized over other elements of international law including international trade and investment law as it applies to access to pharmaceuticals. This paper uses a series of case reports to examine Canada's commitment to this goal. Specifically it examines cases where improved access has been in conflict with increased intellectual property rights. The 6 cases are: Canada's position when 39 pharmaceutical companies took South Africa to court in 1998 over its legislation to allow parallel importation of patented medicines and to regulate the price of medications; the stance that Canada took in the negotiations around the Doha Declaration in 2001; the passage of Canada's Access to Medicines Regime in 2004 and subsequent attempts to amend the legislation in 2011 and 2012; Canada's involvement in the final declaration at the United Nations High-Level meeting on non-communicable diseases in 2012; Canada's views about the terms in the Anti-Counterfeiting Trade Agreement as expressed in 2009; and Canada's 2013 position on the extension of the exemption for least developed countries from having to comply with the terms of the Trade Related Aspects of Intellectual Property Rights Agreement. In the first case Canada was neutral but in the remaining 5 cases Canada prioritized intellectual property rights over access. This position is consistent with how Canada has acted around domestic issues involving intellectual property rights for pharmaceutical products. Canada has supported strengthened rights despite the fact that their touted benefits have not been realized either domestically or in developing countries. As a result Canada has failed in its humanitarian duty to protect the human right to health in the form of safe and low cost medicines for the people in developing countries.

Over the past 35 years, patients have suffered from a largely hidden epidemic of side effects from drugs that usually have few offsetting benefits. The pharmaceutical industry has corrupted the practice of medicine through its influence over what drugs are developed, how they are tested, and how medical knowledge is created. Since 1906, heavy commercial influence has compromised congressional legislation to protect the public from unsafe drugs. The authorization of user fees in 1992 has turned drug companies into the FDA's prime clients, deepening the regulatory and cultural capture of the agency. Industry has demanded shorter average review times and, with less time to thoroughly review evidence, increased hospitalizations and deaths have resulted. Meeting the needs of the drug companies has taken priority over meeting the needs of patients. Unless this corruption of regulatory intent is reversed, the situation will continue to deteriorate. We offer practical suggestions including: separating the funding of clinical trials from their conduct, analysis, and publication; independent FDA leadership; full public funding for all FDA activities; measures to discourage R&D on drugs with few, if any, new clinical benefits; and the creation of a National Drug Safety Board., (© 2013 American Society of Law, Medicine & Ethics, Inc.)

Introduction: The education of medical students should be based on the best clinical information available, rather than on commercial interests. Previous research looking at university-wide conflict of interest (COI) policies used in Canadian medical schools has shown very poor regulation. An analysis of COI policies was undertaken to document the current policy environment in all 17 Canadian medical schools., Methods: A web search was used to initially locate COI policies supplemented by additional information from the deans of each medical school. Strength of policies was rated on a scale of 0 to 2 in 12 categories and also on the presence of enforcement measures. For each school, we report scores for all 12 categories, enforcement measures, and summative scores., Results: COI policies received summative scores that ranged from 0 to 19, with 0 the lowest possible score obtainable and 24 the maximum. The highest mean scores per category were for disclosure and ghostwriting (0.9) and for gifts and scholarships (0.8)., Discussion: This study provides the first comprehensive evaluation of all 17 Canadian medical school-specific COI policies. Our results suggest that the COI policy environment at Canadian medical schools is generally permissive. Policy development is a dynamic process. We therefore encourage all Canadian medical schools to develop restrictive COI policies to ensure that their medical students are educated based on the best clinical evidence available, free of industry biases and COI relationships that may influence the future medical thinking and prescribing practices of medical students in Canada once they graduate.

The Canadian constitution divides the responsibility for pharmaceuticals between the federal and provincial governments. While the provincial governments are responsible for establishing public formularies, the majority of the safety and efficacy information that the provinces use comes from the federal government. We interviewed drug plan officials from eight of the ten provinces and two of three territories regarding their views on the Canadian drug safety system. Here we report on the following categories: the federal drug approval system; the strengths and weaknesses of the federal system of postmarket pharmaceutical safety (i.e., pharmacosurveillance); resources available to support provincial formulary decision making; provincial roles in pharmacosurveillance; how the drug safety system could be improved; and the role of the Drug Safety and Effectiveness Network, a recently established virtual network designed to connect researchers throughout Canada who conduct postmarket drug research. Next, we place the Canadian system within an international context by comparing informational asymmetry between government institutions in the United States and the European Union and by looking at how institutions support each other's roles in sharing information and in jointly developing policy through the International Conference on Harmonization. Finally, we draw on international experiences and suggest potential solutions to the concerns that our key informants have identified.

Background: Pressures on health care budgets have led policy makers to discuss how to balance the provision of costly technologies to populations in need and making coverage decisions under uncertainty. Coverage with evidence development (CED) is being employed to meet these challenges., Methods: Twenty-four interviews were carried out between June 2009 and December 2010 with researchers, decision makers and policy makers from Australia, Canada, United Kingdom and United States. Three phases of coding occurred, the first being manual coding where the interviews were read and notes were taken and nodes were extracted and imputed. NVIVO coding was applied to the interview transcripts, with both broad general searches for word usages and imputed nodes., Results: Four overarching thematic areas emerged out of contextual analysis of the interviews - (1) what constitutes CED; (2) the lack of a systematic approach/governance structure; (3) the role of the pharmaceutical industry and overt political considerations in CED; and (4) alternatives and barriers to CED. We explore these themes and then use concrete examples of CED projects in each of the four countries to illustrate the political issues that our interviewees raised., Conclusion: Until the underlying political nature of CED is recognized then fundamental questions about its usefulness and operation will remain unresolved.

Background: Clinical research affecting how doctors practice medicine is increasingly sponsored by companies that make drugs and medical devices. Previous systematic reviews have found that pharmaceutical industry sponsored studies are more often favorable to the sponsor's product compared with studies with other sources of sponsorship. This review is an update using more stringent methodology and also investigating sponsorship of device studies., Objectives: To investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship., Search Methods: We searched MEDLINE (1948 to September 2010), EMBASE (1980 to September 2010), the Cochrane Methodology Register (Issue 4, 2010) and Web of Science (August 2011). In addition, we searched reference lists of included papers, previous systematic reviews and author files., Selection Criteria: Cross-sectional studies, cohort studies, systematic reviews and meta-analyses that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. We had no language restrictions., Data Collection and Analysis: Two assessors identified potentially relevant papers, and a decision about final inclusion was made by all authors. Two assessors extracted data, and we contacted authors of included papers for additional unpublished data. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether the conclusions agreed with the study results. Two assessors assessed risk of bias of included papers. We calculated pooled risk ratios (RR) for dichotomous data (with 95% confidence intervals)., Main Results: Forty-eight papers were included. Industry sponsored studies more often had favorable efficacy results, risk ratio (RR): 1.24 (95% confidence interval (CI): 1.14 to 1.35), harms results RR: 1.87 (95% CI: 1.54 to 2.27) and conclusions RR: 1.31 (95% CI: 1.20 to 1.44) compared with non-industry sponsored studies. Ten papers reported on sponsorship and effect size, but could not be pooled due to differences in their reporting of data. The results were heterogeneous; five papers found larger effect sizes in industry sponsored studies compared with non-industry sponsored studies and five papers did not find a difference in effect size. Only two papers (including 120 device studies) reported separate data for devices and we did not find a difference between drug and device studies on the association between sponsorship and conclusions (test for interaction, P = 0.23). Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment and follow-up. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.32 (95% CI: 1.05 to 1.65), compared with non-industry sponsored studies. In industry sponsored studies, there was less agreement between the results and the conclusions than in non-industry sponsored studies, RR: 0.84 (95% CI: 0.70 to 1.01)., Authors' Conclusions: Sponsorship of drug and device studies by the manufacturing company leads to more favorable results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.