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Objectives We aimed to systematically review and assess published estimates of the cost of developing new drugs. Methods We sought English language research articles containing original estimates of the cost of drug development that were published from 1980 to 2009, inclusive. We searched seven databases and used citation tracing and expert referral to identify studies. We abstracted qualifying studies for information about methods, data sources, study samples, and key results. Results Thirteen articles were found to meet our inclusion criteria. Estimates of the cost of drug development ranged more than 9-fold, from USD$92 million cash (USD$161 million capitalized) to USD$883.6 million cash (USD$1.8 billion capitalized). Differences in methods, data sources, and time periods explain some of the variation in estimates. Lack of transparency limits many studies. Confidential information provided by unnamed companies about unspecified products forms all or part of the data underlying 10 of the 13 studies. Conclusions Despite three decades of research in this area, no published estimate of the cost of developing a drug can be considered a gold standard. Studies on this topic should be subjected to reasonable audit and disclosure of – at the very least – the drugs which authors purport to provide development cost estimates for.

CONTEXT: Disclosure of conflicts of interest (COIs) from pharmaceutical industry study funding and author-industry financial relationships is sometimes recommended for randomized controlled trials (RCTs) published in biomedical journals. Authors of meta-analyses, however, are not required to report COIs disclosed in original reports of included RCTs. OBJECTIVE: To investigate whether meta-analyses of pharmacological treatments published in high-impact biomedical journals report COIs disclosed in included RCTs. DATA SOURCES AND STUDY SELECTION: We selected the 3 most recent meta-analyses of patented pharmacological treatments published January 2009 through October 2009 in each general medicine journal with an impact factor of at least 10; in high-impact journals in each of the 5 specialty medicine areas with the greatest 2008 global therapeutic sales (oncology, cardiology, respiratory medicine, endocrinology, and gastroenterology); and in the Cochrane Database of Systematic Reviews. DATA EXTRACTION: Two investigators independently extracted data on disclosed study funding, author-industry financial ties, and author employment from each meta-analysis, from RCTs included in each meta-analysis, and on whether meta-analyses reported disclosed COIs of included RCTs. RESULTS: Of 29 meta-analyses reviewed, which included 509 RCTs, only 2 meta-analyses (7%) reported RCT funding sources; and 0 reported RCT author-industry ties or employment by the pharmaceutical industry. Of 318 meta-analyzed RCTs that reported funding sources, 219 (69%) were industry funded; and 91 of 132 (69%) that reported author financial disclosures had 1 or more authors with pharmaceutical industry financial ties. In 7 of the 29 meta-analyses reviewed, 100% of included RCTs had at least 1 form of disclosed COI (pharmaceutical industry funding, author-industry financial ties, or employment), yet only 1 of these 7 meta-analyses reported RCT funding sources, and 0 reported RCT author-industry ties or employment. CONCLUSION: Among a group of meta-analyses of pharmacological treatments published in high-impact biomedical journals, information concerning primary study funding and author COIs for the included RCTs were only rarely reported.

The timeliness with which national regulatory agencies approve new drugs for marketing affects health care professionals and patients. An unnecessarily long approval process delays access to new medications that may improve patients' health status. The author compared drug approval times in Canada, Australia, Sweden, the United Kingdom and the United States.Application and approval dates of new chemical or biological substances (excluding diagnostic products, and new salts, esters, dosage forms and combinations of previously approved substances) approved for marketing in the 5 countries from January 1996 to December 1998 were requested from the relevant pharmaceutical companies. Data on new drug approvals during the study period were also obtained from the national drug regulatory agencies in Canada, Australia and Sweden and from publications of the US Food and Drug Administration.A total of 219 new drugs were identified as being approved in at least one of the countries during the study period: 23 (10.5%) in all 5 countries, 23 (10.5%) in 4, 27 (12.3%) in 3, 42 (19.2%) in 2, and 104 (47.5%) in 1 country. By individual nation, 97 drugs were identified as being approved in Canada, 94 in Australia, 107 in Sweden, 55 in the UK and 123 in the US. Approval times in Canada and Australia were similar (medians 518 and 526 days respectively), but both countries had significantly longer approval times than Sweden (median 371 days), the UK (median 308 days) and the US (median 369 days). This pattern was consistent across all 3 years and for the 23 new drugs approved in all 5 countries during the 3-year period. Median approval times in Canada were similar in all of the reviewing divisions of Health Canada's Therapeutic Product Program (539-574 days) except the Central Nervous System Division (428 days) and the Bureau of Biologics and Radiopharmaceuticals (698 days).Median drug approval times during 1996-1998 decreased by varying amounts from the 1995 values in all 5 countries. However, the median approval time in Canada continues to be significantly longer than the times achieved in Sweden, the UK and the US, and it remains considerably longer than Canada's own target of 355 days for all new drugs.

OBJECTIVE: To determine if revenue generated from pharmaceutical advertisements in medical journals creates potential financial conflicts of interest for nonprofit physician organizations that own those journals. DESIGN: Convenience sample of six professional medical societies and their respective journals. Calculation of pharmaceutical advertising revenue generated by these journals for their respective professional medical societies. METHODS: Random selection of each journal for one month per quarter in calendar year 1996 and tabulation per edition of the average number of pharmaceutical advertising pages for each journal. OUTCOME MEASURES: Published advertising rates were used to estimate pharmaceutical advertising revenue for calendar year 1996 and compared with each organization's gross revenue and membership dues and assessments, based on Internal Revenue Service documents for the last available fiscal year (1995). RESULTS: Estimated pharmaceutical advertising revenue ranged from $715,000 to $18,630,000. Five organizations raised more than 10% of their gross income (range 2% to 30%) from a single journal's pharmaceutical advertising. Four organizations raised as much or more from pharmaceutical advertising as from members (range 17% to 790%). CONCLUSIONS: Potential financial conflicts of interest arising from pharmaceutical advertisements in medical journals may be substantial. The impact on professional societies' financial independence and behavior is unknown.

Some or all of the promotional activities of pharmaceutical companies are typically governed through self-regulatory codes administered by industry associations. However, the conflicts between the commercial objectives and the ethical and scientific goals of promotion can potentially lead to serious weaknesses in the way in which these codes are enforced. This paper focuses on 5 critical aspects involved in the enforcement of codes governing pharmaceutical promotion: mechanisms for recognizing violations, composition of monitoring committees, sanctions for code violations, the quantity and quality of information in reports issued about complaints and code violations, and the circulation these reports receive. The Code of Marketing Practices of the Pharmaceutical Manufacturers Association of Canada (PMAC) has serious weaknesses in all of these areas. Although the Pharmaceutical Advertising Advisory Board's Code of Advertising Acceptance avoids many of the deficiencies of the PMAC code, it, too, has weaknesses. Proposals for strengthening the enforcement of both codes are offered.

Drug therapy is an integral component of modern medical care, and practising physicians are faced with the difficult task of keeping up with rapid changes in pharmacologic treatments. Recent evidence indicates that prescribing practice is often inconsistent with criteria for safety and effectiveness. Surveys indicate that community-based physicians are not satisfied with current sources of information on prescription drugs. The dissemination of printed material alone does not lead to improved prescribing practice, but specific education and feedback strategies can. To improve prescribing practice in Canada we need to systematically evaluate strategies to change prescribing behaviour, to design quality assurance programs based on proven strategies and to develop collaboration and cooperation among providers, manufacturers, governments and the public.

OBJECTIVE: To evaluate the methodologic quality and relevance of references in pharmaceutical advertisements in the Canadian Medical Association Journal (CMAJ). DESIGN: Analytic study. DATA SOURCE: All 114 references cited in the first 22 distinct pharmaceutical advertisements in volume 146 of CMAJ. MAIN OUTCOME MEASURES: Mean methodologic quality score (modified from the 6-point scale used to assess articles in the American College of Physicians' Journal Club) and mean relevance score (based on a new 5-point scale) for all references in each advertisement. MAIN RESULTS: Twenty of the 22 companies responded, sending 78 (90%) of the 87 references requested. The mean methodologic quality score was 58% (95% confidence limits [CL] 51% and 65%) and the mean relevance score 76% (95% CL 72% and 80%). The two mean scores were statistically lower than the acceptable score of 80% (p < 0.05), and the methodologic quality score was outside the preset clinically significant difference of 15%. The poor rating for methodologic quality was primarily because of the citation of references to low-quality review articles and "other" sources (i.e., other than reports of clinical trials). Half of the advertisements had a methodologic quality score of less than 65%, but only five had a relevance score of less than 65%. CONCLUSIONS: Although the relevance of most of the references was within minimal acceptable limits, the methodologic quality was often unacceptable. Because advertisements are an important part of pharmaceutical marketing and education, we suggest that companies develop written standards for their advertisements and monitor their advertisements for adherence to these standards. We also suggest that the Pharmaceutical Advertising Advisory Board develop more stringent guidelines for advertising and that it enforce these guidelines in a consistent, rigorous fashion.

OBJECTIVE: To determine the effect of three types of interaction between physicians and the pharmaceutical industry--company-funded clinical trials, company-sponsored continuing medical education (CME) and information for physicians supplied by pharmaceutical detailers--on orientation and quality of clinical trials, content of CME courses and physicians' prescribing behaviour. DATA SOURCES: MEDLINE and HEALTH searches for English-language articles published from 1978 to 1993, supplemented by material from the author's personal collection. STUDY SELECTION: A total of 227 papers from the MEDLINE and HEALTH searches and about 2000 items from the author's library were initially reviewed. The following selection criteria were used: studies conducted in Australia, Canada, New Zealand, Britain and the United States; studies conducted after 1977; quantitative surveys containing details of the survey methods; studies on the orientation and quality of company-funded clinical trials and on the content of CME courses giving explicit criteria used in the evaluation; and reports on the outcome of interactions stating how the outcomes were assessed. Thirty-six studies met these criteria. DATA EXTRACTION: Information was extracted on five topics: physicians' attitudes toward drug industry interactions, frequency with which physicians participate in the interactions, orientation and quality of company-funded clinical trials, content of company-sponsored CME courses and changes in physicians' prescribing behaviour as a result of an interaction. DATA SYNTHESIS: Although most physicians participate only occasionally in company-sponsored clinical trials, most see detailers and attend company-sponsored CME courses. However, physicians do not have a very high opinion of the information from detailers or of company-sponsored CME events. Many doctors regard pharmaceutical companies as an important source of funding for clinical trials, but they also have concerns about accepting money from this source. Company funding of clinical trials may affect the quality of the trials and the types of research that physicians undertake. Company-sponsored CME courses may have a commercial bias even if conducted under guidelines designed to ensure the independence of the event. All three types of interactions affect physicians' prescribing behaviour and, in the case of obtaining information from detailers, physicians' prescribing practices are less appropriate as a result of the interaction. CONCLUSIONS: Physicians are affected by their interactions with the pharmaceutical industry. Further research needs to be done in most cases to determine whether such interactions lead to more or less appropriate prescribing practices. The CMA's guidelines on this topic should be evaluated to see whether they are effective in controlling physician-industry interactions. Further measures may be necessary if the guidelines fail to prevent negative effects on prescribing practices.

Forty-seven patients older than 65 years were randomly selected for structured chart review of all long-term medications documented during the prior year and the number of instances of potentially undesirable prescribing for each patient. A trained nurse subsequently made home visits to assess all long-term medications used regularly during the same period. Forty-five percent of elderly patients had one or more instances of potentially undesirable drug use, all of which appeared to be readily remediable. Commercial drug interaction software identified less than half of the potentially undesirable instances.

To compare how well graduates of a self-directed, problem-based undergraduate curriculum (at McMaster University [MU], Hamilton, Ont.) and those of a traditional curriculum (at the University of Toronto [UT]) who go on to primary care careers keep up to date with current clinical practice guidelines.Analytic survey. Management of hypertension was chosen as an appropriate topic to assess guideline adherence. An updated version of a previously validated questionnaire was mailed to the participants for self-completion.Private primary care practices in southern Ontario.A random sample of 48 MU graduates and 48 UT graduates, stratified for year of graduation (1974 to 1985) and sex, who were in family or general practice in Ontario; 87% of the eligible subjects in each group responded.Overall and component-specific scores; analysis was blind to study group.The overall mean scores were 56 (68%) of a possible 82 for the MU graduates and 51 (62%) for the UT graduates (difference between the means 5, 95% confidence interval 1.9 to 8.2; p0.01). Multivariate linear regression analysis of seven factors that might affect questionnaire scores revealed that only the medical school was statistically significant (p0.01). The MU graduates had significantly higher mean scores than the UT graduates for two components of the questionnaire: knowledge of recommended blood pressures for treatment (p0.05) and successful approaches to enhance compliance (p0.005). The trends were similar for the other components but but were not significant.The graduates of a problem-based, self-directed undergraduate curriculum are more up to date in knowledge of the management of hypertension than graduates of a traditional curriculum.

OBJECTIVE: To analyse the potential effect of generic drug competition on prices in Ontario to assess the costs and benefits associated with Bill C-22 (An Act to amend the Patent Act). DESIGN: Comparison of the cost of the least and most expensive versions of all products sold by more than one manufacturer in 1991. The number of brand-name and generic drug companies marketing each of the products was recorded. RESULTS: Of 1599 products 437 (27.3%) were made by more than one company. Almost half (44.6%) of the 437 were sold by two companies. The more companies that sold a drug the greater the difference in price between the least and most expensive versions. Similarly, as the proportion of generic drug companies in competition increased, the greater the price difference. When competition was between generic drug companies only, the price spread was smaller than when it was between brand-name drug companies only. CONCLUSIONS: Generic drug competition can result in savings to the Ontario Drug Benefit Plan. A more in-depth analysis of the potential savings is necessary to fully assess the costs and benefits associated with Bill C-22.