The relationship between study sponsorship, risks of bias, and research outcomes in atrazine exposure studies conducted in non-human animals: Systematic review and meta-analysis.

BACKGROUND: A critical component of systematic review methodology is the assessment of the risks of bias of studies that are included in the review. There is controversy about whether funding source should be included in a risk of bias assessment of animal toxicology studies. OBJECTIVE: To determine whether industry research sponsorship is associated with methodological biases, the results, or conclusions of animal studies examining the effect of exposure to atrazine on reproductive or developmental outcomes. METHODS: We searched multiple electronic databases and the reference lists of relevant articles to identify original research studies examining the effect of any dose of atrazine exposure at any life stage on reproduction or development in non-human animals. We compared methodological risks of bias, the conclusions of the studies, the statistical significance of the findings, and the magnitude of effect estimates between industry sponsored and non-industry sponsored studies. RESULTS: Fifty-one studies met the inclusion criteria. There were no differences in methodological risks of bias in industry versus non-industry sponsored studies. 39 studies tested environmentally relevant concentrations of atrazine (11 industry sponsored, 24 non-industry sponsored, 4 with no funding disclosures). Non-industry sponsored studies (12/24, 50.0%) were more likely to conclude that atrazine was harmful compared to industry sponsored studies (2/11, 18.1%) (p value=0.07). A higher proportion of non-industry sponsored studies reported statistically significant harmful effects (8/24, 33.3%) compared to industry-sponsored studies (1/11; 9.1%) (p value=0.13). The association of industry sponsorship with decreased effect sizes for harm outcomes was inconclusive. CONCLUSION: Our findings support the inclusion of research sponsorship as a risk of bias criterion in tools used to assess risks of bias in animal studies for systematic reviews. The reporting of other empirically based risk of bias criteria for animal studies, such as blinded outcome assessment, randomization, and all animals included in analyses, needs to improve to facilitate the assessment of studies for systematic reviews.

The role of public participation in public health initiatives: an analysis of the WHO Framework Convention on Tobacco Control.

This is a content analysis of 489 written documents and 142 hearing testimonies, submitted to the World Health Organisation (WHO), regarding the Framework Convention on Tobacco Control (FCTC) during the comment period of 2000. Our aim was to consider the benefits and limitations of inviting public participation. We found that, overall, those who offered commentary were in support of the FCTC and any ensuing treaty, especially if it protected children. The minority who opposed the treaty argued that restrictions on tobacco trade would further damage the economies of poor nations that are financially dependent upon tobacco. The FCTC that was adopted at the World Health Assembly in May 2003 addressed many of the concerns raised by the public in written commentary and hearing testimony: children and youth; advertising and sponsorship; tobacco product labelling; second-hand smoke; taxes; smuggling; liability; tobacco product regulation; and the involvement of non-government organisations (NGOs). We conclude that the benefits of public participation in public health policy formation are numerous, including levelling the playing field for public health activists and NGOs, building the expertise of advocates that can be generalised to other public health efforts, giving the political process legitimacy and credibility, as well as coalition building and grassroots momentum.

Philip Morris involvement in the development of an air quality laboratory in El Salvador.

BACKGROUND: The tobacco industry has organised research institutions to generate misleading data on indoor air quality, including second-hand smoke exposure and health effects. OBJECTIVES: To describe tobacco industry involvement in the organisation and financial support of an air quality research laboratory in El Salvador. METHODS: Tobacco industry documents on the internet were systematically searched from August 2007 to February 2008 for air quality studies undertaken in El Salvador, and laboratory personnel were interviewed. RESULTS: Philip Morris sought to establish a network of air quality laboratories throughout Latin America. In El Salvador, in 1997, through Tabacalera de El Salvador (a subsidiary of Philip Morris) and the Salvadoran Foundation for Economic Development (FUSADES), the industry organised an air quality research laboratory. FUSADES was part of the industry's Latin American Scientific Network, which consisted of doctors hired as consultants who would send air samples from their research to FUSADES. Philip Morris Scientific Affairs personnel hired LabStat, a Canadian-based laboratory, to provide technical assistance to FUSADES (train and assist the laboratory in air quality measurements). In addition, the Washington-based HMS Group successfully implemented a plan to upgrade the laboratory and obtain international certifications. HMS Group also assisted in searching for sustainable funding for FUSADES, including seeking funds from international aid for Hurricane Mitch. CONCLUSION: Air quality studies that have used the FUSADES laboratory should be carefully interpreted, given the support that this laboratory received from Philip Morris.

WITHDRAWN: Printed educational materials: effects on professional practice and health care outcomes.

BACKGROUND: It is often assumed that merely providing information in an accessible form will influence practice. Although such a strategy is still widely used in an attempt to change behaviour, there is a growing awareness that simply providing information may not lead to appropriate changes in the practice of health care professionals. OBJECTIVES: To assess the effects of printed educational materials in improving the behaviour of health care professionals and patient outcomes. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register, reference lists of articles, and contacted content area experts. SELECTION CRITERIA: Randomised trials, interrupted time series analyses and non equivalent group designs with pre-post measures of interventions comparing 1. Printed educational materials versus a non-intervention control; and 2. Printed educational materials plus additional implementation strategies versus printed educational materials alone. The participants were any health care professionals provided with printed educational materials aimed at improving their practice and/or patient outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Eleven studies were included involving more than 1848 physicians. It proved impractical to examine the impact of interventions quantitatively because of poor reporting of results and inappropriate primary analyses. Nine studies examined comparison 1. Estimates of the benefit from printed educational materials ranged from -3% to 243.4% for provider outcomes, and from -16.1% to 175.6% for patient outcomes, although the practical importance of these changes is, at best, small. Six studies (seven comparisons) examined comparison 2. Benefits attributable to additional interventions ranged from -11.8% to 92.7% for professional behaviour, and -24.4% to 74.5% for patient outcomes. Two of the 14 estimates of professional behaviour, and two of the 11 estimates of patient outcomes were statistically significant. AUTHORS' CONCLUSIONS: The effects of printed educational materials compared with no active intervention appear small and of uncertain clinical significance. These conclusions should be viewed as tentative due to the poor reporting of results and inappropriate primary analyses. The additional impact of more active interventions produced mixed results. Audit and feedback and conferences/workshops did not appear to produce substantial changes in practice; the effects in the evaluations of educational outreach visits and opinion leaders were larger and likely to be of practical importance. None of the studies included full economic analyses, and thus it is unclear to what extent the effects of any of the interventions may be worth the costs involved.

The limits of competing interest disclosures.

OBJECTIVE: To assess the effectiveness of conflict of interest disclosure policies by comparing a competing interests disclosure statement that met the requirements established by the journal in a 2003 article on health effects of secondhand smoke based on the American Cancer Society CPS-I dataset with internal tobacco industry documents describing financial ties between the tobacco industry and authors of the study. DESIGN: Descriptive analysis of internal tobacco industry documents retrieved from the Legacy Tobacco Documents Library, University of California, San Francisco. RESULTS: Meeting the requirements for financial disclosure established by the journal did not provide the reader with a full picture of the tobacco industry's involvement with the study authors. The tobacco industry documents reveal that the authors had long standing financial and other working relationships with the tobacco industry. CONCLUSION: These findings are another example of how simply requiring authors to disclose financial ties with the tobacco industry may not be adequate to give readers (and reviewers) a full picture of the author's relationship with the tobacco industry. The documents also reveal that the industry funds research to enhance its credibility and endeavours to work with respected scientists to advance its goals. These findings question the adequacy of current journal policies regarding competing interest disclosures and the acceptability of tobacco industry funding for academic research.

A nicotine delivery device without the nicotine? Tobacco industry development of low nicotine cigarettes.

BACKGROUND: Defining harm reduction and regulating potentially reduced exposure products (PREPs), including low nicotine products, are key issues in tobacco control policy. The US Congress has been considering legislation authorising the Food and Drug Administration (FDA) to regulate tobacco products. OBJECTIVE: To investigate tobacco industry perceptions, interests, motivations, and knowledge regarding the marketability of low nicotine tobacco products. METHODS: Qualitative analysis of internal tobacco industry documents identified in the Legacy Tobacco Documents Library between February 2002 and June 2004. Search terms included low-, no-, reduced-nicotine; denicotinization; low-, reduced- alkaloids; Next; de-nic; and key names of people, organisations, projects, and their common abbreviations and acronyms. RESULTS: The tobacco industry has made repeated efforts to develop low nicotine cigarettes. Reasons for doing so include consumer appeal and economic importance in a highly competitive cigarette market for "healthier" products. The industry considered the development of a new "denic" market segment a critical challenge. CONCLUSIONS: The tobacco industry exploits consumer misunderstanding of the health effects of nicotine in development and marketing efforts. The industry has risked the development of a less addictive product to expand the market reach of tobacco products based on perceived health benefits and appeal to quitters.

Creating a text data-mining application for use in public health informatics.

Recent litigation and the Master Settlement Agreement of 1998 have made millions of tobacco industry internal documents available on the Internet (http://legacy.library.ucsf.edu). The Legacy interface, housed at the University of California, San Francisco, is based on a traditional information retrieval model in which documents are indexed and retrieved based on user-specified queries. One problem with the Legacy interface is information overload. In an attempt to ease this problem, we are developing a text-mining interface to enable exploratory analysis and discovery of information from collections of data. Users could uncover new patterns and concepts and thus text mining could result in searches that are targeted and specific, which would decrease information overload. In order to determine information needs, nine in-depth interviews with regular users of the Legacy interface were conducted. Results show that participants identified clustering as a useful tool in identifying and extracting key concepts and identified the need to recognize relationships between terms and concepts within the data. We encourage researchers who are developing text-mining interfaces to survey the users to learn what particular aspects of their research could be enhanced by text mining.

Systematic reviews of the effectiveness of quality improvement strategies and programmes.

Systematic reviews provide the best evidence on the effectiveness of healthcare interventions including quality improvement strategies. The methods of systematic review of individual patient randomised trials of healthcare interventions are well developed. We discuss methodological and practice issues that need to be considered when undertaking systematic reviews of quality improvement strategies including developing a review protocol, identifying and screening evidence sources, quality assessment and data abstraction, analytical methods, reporting systematic reviews, and appraising systematic reviews. This paper builds on our experiences within the Cochrane Effective Practice and Organisation of Care (EPOC) review group.

Science in regulatory policy making: case studies in the development of workplace smoking restrictions.

OBJECTIVE: To study the role of science related and other arguments in the development of workplace smoking regulations. DESIGN: Case study, content analysis SUBJECTS: Written commentaries and hearing transcripts on proposed indoor air regulations in Maryland and Washington. MAIN OUTCOME MEASURES: We coded each written commentary and hearing testimony for position toward the regulation, affiliation of the person submitting it, criteria used to evaluate science and scientific, ideological, economic, political, engineering and procedural arguments. RESULTS: In both states, opposition to the regulations came primarily from the tobacco industry, small businesses, and business organisations and appeared to be coordinated. There was little coordination of public health support for the regulations. Arguments about science were used more often by those opposed to the regulations than by those in favour. Supporters emphasised the quantity of the evidence, while opponents criticised its reliability, validity, and quality. Arguments not related to science (61% of total arguments; 459/751), were more common than scientific arguments (39% of total arguments; 292/751). Economic and ideological arguments were used to a similar extent by regulation supporters and opponents. CONCLUSIONS: Advocates can support health related regulations by submitting commentary emphasising the sound research base for regulation and countering criticisms of research. National coordination of these efforts could avoid duplication of effort and make more efficient use of limited public health resources.

Changing provider behavior: an overview of systematic reviews of interventions.

BACKGROUND: Increasing recognition of the failure to translate research findings into practice has led to greater awareness of the importance of using active dissemination and implementation strategies. Although there is a growing body of research evidence about the effectiveness of different strategies, this is not easily accessible to policy makers and professionals. OBJECTIVES: To identify, appraise, and synthesize systematic reviews of professional educational or quality assurance interventions to improve quality of care. RESEARCH DESIGN: An overview was made of systematic reviews of professional behavior change interventions published between 1966 and 1998. RESULTS: Forty-one reviews were identified covering a wide range of interventions and behaviors. In general, passive approaches are generally ineffective and unlikely to result in behavior change. Most other interventions are effective under some circumstances; none are effective under all circumstances. Promising approaches include educational outreach (for prescribing) and reminders. Multifaceted interventions targeting different barriers to change are more likely to be effective than single interventions. CONCLUSIONS: Although the current evidence base is incomplete, it provides valuable insights into the likely effectiveness of different interventions. Future quality improvement or educational activities should be informed by the findings of systematic reviews of professional behavior change interventions.

Policy makers' perspectives on tobacco control advocates' roles in regulation development.

OBJECTIVE: To identify, from policy makers' perspectives, strategies that enhance tobacco control advocates' effectiveness in the regulatory arena. DESIGN: Key informant interview component of a comparative case study of regulatory agencies in the USA. SUBJECTS: Policy makers involved in the development of four regulatory tobacco control policies (three state and one federal). METHODS: Interviews of policy makers, field notes, and deliberation minutes were coded inductively. RESULTS: Policy makers considered both written commentary and public testimony when developing tobacco control regulations. They triaged written commentary based upon whether the document was from a peer reviewed journal, a summary of research evidence, or from a source considered credible. They coped with in-person testimony by avoiding being diverted from the scientific evidence, and by assessing the presenters' credibility. Policy makers suggested that tobacco control advocates should: present science in a format that is well organised and easily absorbed; engage scientific experts to participate in the regulatory process; and lobby to support the tobacco control efforts of the regulatory agency. CONCLUSIONS: There is an important role for tobacco control advocates in the policy development process in regulatory agencies.

Cigar magazines: using tobacco to sell a lifestyle.

OBJECTIVE: To assess the content of two cigar "lifestyle" magazines, Cigar Aficionado and Smoke. DESIGN: Content analysis of cigar focused articles. SUBJECTS: Cigar focused articles (n = 353) from Cigar Aficionado and Smoke magazines. MAIN OUTCOME MEASURES: Primary focus; mention of health effects, environmental tobacco smoke, or scientific research; quotation and description of individuals; characteristics such as sex, age, ethnicity, smoking status, affiliation, and stance towards cigars; and overall image of cigars. RESULTS: Cigar business-focused articles were the largest category (40%, n = 143), followed by articles about cigar events (12%, n = 42). Notable were articles featuring cigar benefits to raise money for health charities. Celebrities were featured in 34% (n = 121) of articles and 96% (n = 271) favoured cigar use. Only four (1%) articles featured health effects of cigars as a primary focus. CONCLUSIONS: Cigar Aficionado and Smoke broke new ground in tobacco marketing by combining promotion of product, lifestyle, and industry in the same vehicle and linking the medium directly to product related events that extended its reach. The creation and marketing of new tobacco use sites challenges the increasing "isolation" of smokers, and positions cigar use as a socially welcome relief from restrictions. Public health advocates should anticipate and challenge other new tobacco marketing vehicles as communications technologies advance and public spaces for smoking shrink.

Taking advantage of the explosion of systematic reviews: an efficient MEDLINE search strategy.

CONTEXT: Systematic reviews of the literature are an important resource for clinicians. Unfortunately, the few published strategies for identifying these articles involve MEDLINE interfaces not widely available outside of academic medicine. In addition, the performance of these strategies is unknown. OBJECTIVE: To develop and evaluate a search strategy for identifying systematic reviews by using a publicly available MEDLINE interface (PubMed). DESIGN: Diagnostic test assessment. DEFINITION OF SENSITIVITY: The proportion of recognized systematic reviews (indexed in the Cochrane Library's Database of Abstracts of Reviews of Effectiveness [DARE] or in ACP Journal Club) that are identified by the search strategy. DEFINITION OF POSITIVE PREDICTIVE VALUE: The proportion of articles identified in one of three sample searches (screening for colorectal cancer, thrombolytic therapy for venous thromboembolism, and treatment of dementia) that meet a minimum definition of systematic review. RESULTS: Our PubMed search strategy identified 93 of 100 DARE-indexed systematic reviews, a sensitivity of 93% (95% CI, 86% to 97%). For the sample of systematic reviews drawn from ACP Journal Club (n = 103), the PubMed strategy achieved a sensitivity of 97% (CI, 91% to 99%). When the three sample search strings were used, approximately 50% of retrieved articles met our minimum definition of systematic review. In contrast, the similar precision of a PubMed search restricted to review-type articles (as indexed by MEDLINE) was less than 10%. CONCLUSIONS: This search strategy identified most systematic reviews without over-whelming users with numerous false-positive results. A "single-click" filter based on this strategy is now available as part of the Clinical Queries feature of PubMed.

The cigar revival and the popular press: a content analysis, 1987-1997.

OBJECTIVES: The purpose of this study was to examine print media coverage of cigars during the period 1987 to 1997. METHODS: A content analysis of 790 cigar-focused newspaper and magazine articles was conducted. RESULTS: Cigar-focused articles increased substantially over the study period, paralleling increased cigar consumption. Articles focused on cigar business (39%) and events (19%). Only 4% of articles focused on health effects. Sixty-two percent portrayed cigars favorably. The tobacco industry was mentioned in 54% of articles and portrayed positively in 78%. Forty-two percent of the individuals quoted or described in articles were affiliated with the tobacco industry; only 5% were government/public health figures. CONCLUSIONS: Print coverage of cigars failed to communicate health risk messages and contributed to positive images of cigars.

Lessons learned from the tobacco industry's efforts to prevent the passage of a workplace smoking regulation.

OBJECTIVES: This study assessed the implementation of tobacco industry strategies to prevent a workplace smoking regulation. METHODS: Tobacco industry internal documents were identified; hearing transcripts for the affiliations, arguments, and positions regarding the regulation of testifiers were coded; and media coverage was analyzed. RESULTS: Tobacco industry strategies sought to increase business participation and economic discussions at public hearings and to promote unfavorable media coverage of the regulation. The percentage of business representatives opposing the regulation grew from 18% (5 to 28) to 57% (13 of 23) between the hearings. Economic arguments opposing the regulation rose from 25% (7 of 28) to 70% (16 of 23). Press coverage was neutral and did not increase during the period of the regulatory hearings. CONCLUSIONS: The tobacco industry was successful in implementing 2 of its 3 strategies but was not able to prevent passage of the comprehensive workplace regulation.

Assessing faculty financial relationships with industry: A case study.

CONTEXT: A growing number of academic researchers receive industry funding for clinical and basic research, but little is known about the personal financial relationships of researchers with their industry sponsors. OBJECTIVES: To assess the extent to which faculty researchers have personal financial relationships with the sponsors of their research, the nature of those financial relationships, and efforts made at the institutional level to address disclosed financial relationships and perceived conflicts of interest. DESIGN AND SETTING: Case study of the University of California, San Francisco (UCSF). Data sources included disclosure forms and official documents maintained by the UCSF Office of Research Administration from December 1980 to October 1999, including decisions made by the UCSF Chancellor's Advisory Panel on Relations with Industry. MAIN OUTCOME MEASURES: Number and types of personal financial relationships with external sponsors (positive financial disclosures from all clinical, basic, or social science faculty who were principal investigators), amount of annual income received from sponsors, and decisions and management strategies used by the advisory panel. RESULTS: By 1999, almost 7.6% of faculty investigators reported personal financial ties with sponsors of their research. Throughout the study period, 34% of disclosed relationships involved paid speaking engagements (range, $250-$20, 000 per year), 33% involved consulting agreements between researcher and sponsor (range, <$1000-$120,000 per year), and 32% involved the investigator holding a position on a scientific advisory board or board of directors. Fourteen percent involved equity ownership, and 12% involved multiple relationships. The advisory panel recommended managing perceived conflicts of interest in 26% of the cases, including recommending the sale of stock, refusing additional payment for talks, resigning from a management position, or naming a new principal investigator for a project. CONCLUSIONS: Faculty researchers are increasingly involved in financial relationships with their research sponsors. Guidelines for what constitutes a conflict and how the conflict should be managed are needed if researchers are to have consistent standards of behavior among institutions. JAMA. 2000;284:2209-2214.