Clinical Practice and the Pharmaceutical Industry 

Pharmaceutical industries &Sponsorship of Researches

fact that the pharmaceutical industry now spends more on medical research than do the National Institutes of Health in the United States.

The report rejected a claim by critics of the pharmaceutical industry that drug companies spent more on advertising than on research and development. The report found that drug makers spent much more on research. Last year,it said companies spent $30.3bn on research and

development and $19.1bn on all promotion activities.including $2.7bn for advertising aimed at consumers

Congress

Cost Benefit

Effectiveness

Promotion

Pharmaceutical industry sponsorship and 

research outcome and quality

Physicians phamaceutical companies interrelations

•Representatives

•Funds

ResearchesScientific activities

Influences on general practitioners' decision to prescribe new drugs-the importance of who says what.

Prosser H, Almond S, Walley T.

Prescribing Research Group, Department of Pharmacology and Therapeutics, The Infirmary, 70 Pembroke Place, Liverpool L69 3GF and Royal Liverpool University Hospital, Liverpool L7 8XP, UK.

Prescribing of new drugs is not simply related to biomedical evaluation and critical appraisal but, more importantly, to the mode of exposure to pharmacological information and social influences on decision making. Viewed within this broad context, prescribing variation becomes more understandable. Findings have implications for the implementation of evidence-based medicine, which requires a multifaceted approach.

The methods of influence used include: B1. Gifts (reciprocal obligations)B2. Appeals to authorityB3. Social validation (Appeals to conformity)B4. Liking / friendshipB5. Commitment consistencyB6. ScarcityB7. Appeals to sympathyB8. Magic wordsB9. Images that appeal to desires B10. Repetition for agenda setting 

Rules and Guidelines on Doctors’ relations with drug companies

Elizabeth Wager

Code of conduct & complaint

Prohibit inducements

Commercially funded research

summary

Journal condition Unsupressed data

Guidance and good publication

Dialogue between the interestedparties

summary

Pharmaceutical industry sponsorship and 

research outcome and quality: systematic review 

British Medical Journal 31may03

Joel Lexchin, associate professor1, Lisa A Bero, professor2, Benjamin Djulbegovic, associate professor3, Otavio Clark, chief of clinical oncology section4

1 School of Health Policy and Management, York University, Toronto, ON, Canada M3J 1P3, 2 Department of Clinical Pharmacy and Institute for Health Policy Studies, University of California at San Francisco, San Francisco, CA 94118, USA,3 Interdisciplinary Oncology Program, H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA, 4 Instituto do Radium de Campinas, 13075-460 Campinas-SP, BrazilCorrespondence to: J Lexchin joel.lexchin@utoronto.ca 

An increasing number of clinical trials at all stages in a product's life cycle are funded by the pharmaceutical industry

Results that are unfavourable to the sponsor—that is, trials that find a drug is less clinically effective or cost effective or less safe than other drugs used to treat the same condition—can pose considerable financial risks to companies.

Possibility of

Pressure to show that the drug causes a favourable outcome may result in biases in design, outcome, and reporting of industry sponsored research.

Exclusion of

Possible biases

I. Clinical trialsPROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL (RCT).A. STATISTICAL CONSIDERATIONSB. ETHICAL CONSIDERATIONSC. STUDY POPULATIONSD. ENDPOINT ASSESSMENTE. ANALYSIS

recent systematic review of the impact of financial conflicts on biomedical research found that studies financed by industry, although as rigorous as other studies, always found outcomes favourable to the sponsoring company. However, this review looked for papers published only in English, excluded reports in letters and abstracts, and looked at studies funded by other industries.

Objective

To investigate whether funding of drug studies by the pharmaceutical industry is associated with outcomes that are favourable to the funder and whether the methods of trials funded by pharmaceutical companies differ from the methods in trials with other sources of support.

MethodsMedline (January 1966 to December 2002) and Embase (January 1980 to December 2002) searches were supplemented with material identified in the references and in the authors' personal files. Data were independently abstracted by three of the authors and disagreements were resolved by consensus.

Results

30 studies were included. Research funded by drug companies was less likely to be published than research funded by other sources. Studies sponsored by pharmaceutical companies were more likely to have outcomes favouring the sponsor than were studies with other sponsors (odds ratio 4.05; 95% confidence interval 2.98 to 5.51; 18 comparisons). None of the 13 studies that analysed methods reported that studies funded by industry was of poorer quality.

Conclusion

Systematic bias favours products which are made by the company funding the research. Explanations include the selection of an inappropriate comparator to the product being investigated and publication bias.

Relationships Between Authors of Clinical Practice Guidelines and the Pharmaceutical Industry Niteesh K. Choudhry, MD, FRCPC; Henry Thomas Stelfox, MD, FRCPC; Allan S. Detsky, MD, PhD, FRCPC

JAMA. 2002;287:612-617

JAMA. 2002;287:612-617

Eighty-seven percent 87 % of authors had some form of interaction with the pharmaceutical industry.

Fifty-eight percent 58 % had received financial support to perform research and

38% had served as employees or consultants for a pharmaceutical company.

CPG authors interacted with 10.5 different companies. Overall, an average of 81% (95% confidence interval, 70%-92%) of authors per CPG had interactions. Similarly, all of the CPGs for 7 of the 10 diseases included in our study had at least 1 author who had some interaction. Fifty-nine 59% percent had relationships with companies whose drugs were considered in the guideline they authored, and of these authors, 96% had relationships that predated the guideline creation process.

JAMA. 2002;287:612-617

Fifty-five percent of respondents indicated that the guideline process with which they were involved had no formal process for declaring these relationships. In published versions of the CPGs, specific declarations regarding the personal financial interactions of individual authors with the pharmaceutical industry were made in only 2 cases. Seven percent thought that their own relationships with the pharmaceutical industry influenced the recommendations and 19% thought that their coauthors' recommendations were influenced by their relationships.

JAMA. 2002;287:612-617

Interpretation bias  UKPDSSeeing what you want to see in randomised controlled trials James McCormack and Trisha Greenhalgh, 

BMJ 2000;320:1720-1723 ( 24 June) 

Nevertheless, many authors, journal editors, and the wider scientific community interpreted the study as providing evidence of the benefit of intensive glucose control

UKPDSSeeing what you want to see in randomised controlled trials James McCormack and Trisha Greenhalgh

Why Consider Economic Research

•Alone research by Pharmaceutical Lab

•Total Funds of scientific research

•Share witn others

Type of Funds

ECONOMIC EVALUATIONS: REAL OR IMAGINED?    

Correspondence to:Michael Drummond Marco BarbieriCentre for Health Economics Centre for Health EconomicsUniversity of York University of YorkHeslington, York Y010 5DD, UK Heslington, York Y010 5DD,UKTel: +44 1904 433709 Tel: +44 1904 434264Fax: +44 1904 433644 Fax: +44 1904 433644e-mail: chedir@york.ac.uk e-mail: mb35@york.ac.uk

 Stelfox et al. (1998) Review of English-language medical literature (1995-1996) about the safety of calcium channel antagonists. 70 articles found: 30 supportive of calcium-channels antagonist, 17 neutral, 23 critical. 96% of the supportive authors had financial relationship with manufacturers of calcium-channel antagonists, as compared with 60% of neutral and 37 of the critical authors. The association was statistically significant. 

Cho and Bero (1996)Comparison of drug studies published in symposium proceedings that are sponsored by drug companies with articles published in their parent medical journals.The percentage in favour of the drug of interest was 98% for articles with drug companies support and 79% for articles without drug companies support. The difference was statistically significant.   

Davidson RA (1986)Review of randomised clinical trials in different areas.107 published trials were analysed. 71% of trials favoured new therapies; 43% of these were funded by pharmaceutical firms. Of 31% of trials favouring the traditional therapy, only four (13%) were supported by drug companies. There was a statistically significant association between the source of funding and the outcome of the study. 

Rochon et al. (1994)Review of publications of manufactures-supported trial of NSAIDs (1987-1990)52 publications representing 56 trials were found. In all 56 trials the manufacturer-associated drug was reported as comparable (71.4%) or superior (28.6%) to the comparison drug. 

Gazzaniga and Garattini (1992)Review of 7 pharmacoeconomic studies on cholesterol-lowering agentsLack of methodological rigour in some part of the analyses, but this is not necessary linked to industrial sponsorship. The role of sponsor played by drug companies in 5 of the 7 studies did not seem to have significantly affected the quality of the results.

Sacristan et al. (1997)Review of economic studies published over the period 1988 to 1994. Analysis of publication bias.22 out of 24 studies (83%) published in PharmacoEconomics reported positive results, with 83% of them sponsored by drug companies. 34 out of 69 studies (49%) published in general medical journals reported positive findings, with 74% of them sponsored by government agencies. The difference in percentage of positive results between PharmacoEconomics and general medical journals was statistically significant. 

Drummond et al. (1997)Survey of decision-makers’ atitudes to economic evaluation conducted in the UK.59% of responders cited the lack of credibility of industry-sponsored studies as an obstacle to the use of the study, with 8% of respondents identifying this as the most important obstacle. By contrast, the possibility that government studies were not credible was identified as a problem by only 9% of respondents, with less than 1% identifying this as the most important. 

Azimi and Welch (1998)Comparison of cost-effectiveness analyses sponsored by drug companies with those sponsored by non-profit organisationsIndustry-financed cost-effectiveness analyses were more likely to support additional expenditures with investigational drugs than standard treatments.   

This publication bias can only be addressed by increasing the funding for economic evaluations of medicines from other, mainly public, sources.

ECONOMIC EVALUATIONS: REAL OR IMAGINED?

National Codes, Associattion of British Pharmaceutical industry (ABPI), Medicines Australia and Pharmaceutical Research and Manufacturers of America

France, legal code de la sante Publique (article L4113-6) Prohibit Physician from receiving benefitsmore than 30 euros (illegal payments)sanction 75 000 euros and a two yearsprison sentence