how drug companies systematically manipulate scientific research in pursuit of profit

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http://www.healthmatters.org.uk/stories/morgan.html

 

Health Matters issue 43 Winter 2000/01 Buying science, selling drugsSteve

Morgan, Morris Barer and Robert Evans explain how drug companies systematically

manipulate scientific research in pursuit of profit

According to standard economic theory the behaviour of private firms is driven

by the desire to make as much money as possible. For drug companies, which have

extraordinarily high fixed costs and low variable costs of production, the route

to profitability is through sales.

 

At least part of the selling process in the pharmaceutical industry involves

creating and disseminating scientific evidence about the merits of a product. In

an ideal world, corporate investment in clinical research would facilitate

prescribing decisions based on objective evaluations of scientific evidence on

safety, efficacy and cost-effectiveness. Reality, alas, intrudes.

 

Pharmaceutical companies are not educational charities, investing in

disinterested product evaluation. Science and objectivity are of interest to a

private, for-profit corporation only insofar as they further the drive for

profits. In fact, to the discomfort of many economists, economic theory does not

rule out destroying scientific information or producing false information as a

means of pursuing the profit objective, just as it does not rule out

contaminating the environment, using child labour or selling known carcinogens.

Consider, for example, the long and sordid history of the tobacco industry.

 

In the pharmaceutical sector, it may be profitable for a firm to promote bias in

the creation, evaluation and dissemination of information so as to encourage

sales – provided that such behaviour is either undetected or carries penalties

that are outweighed by its profit potential.

 

The picture that has emerged from the clinical sciences overwhelmingly suggests

that such practices are profitable because they routinely occur in the

pharmaceutical industry.1 Despite scientific pretences, drug companies have

injected various forms of bias into virtually every aspect of the product

evaluation process.

 

They begin at the front line, courting practising physicians – most notoriously

by proffering gifts: complimentary meals, travel, gifts and entertainment all

have a documented impact on prescribing, increasing the use of the sponsor's

products regardless of appropriateness.2,3 If gifts and other inducements did

not affect prescribing behaviour, economic theory (and common sense) predicts

that they would not be offered.

 

Not every physician accepts gifts and not all of those who accept them are

influenced. Further, even physicians most likely to believe drug manufacturers'

promotional claims will also be influenced by other sources of information. For,

along with other potentially competing interests, the physician's primary duty

of trust is to the patient. This makes it imperative for drug companies to

influence, to whatever extent they profitably can, the ostensibly

non-promotional sources of drug-related information.

 

Medical associations have long been a third-party source of drug-related

information for prescribers. Prescribing information, cautions, and guidelines

disseminated under the auspices of medical associations carry the implicit

scientific credibility that such endorsement brings – so drug companies have

invested tremendous resources in marketing activities channelled through medical

associations. In the process, drug-makers have allied the medical profession as

a whole just as they have allied individual physicians. Through grants,

advertising and other sources of financial support, medical associations are

heavily reliant on the pharmaceutical industry as a source of funding, placing

the associations in an obvious conflict of interest.4-7

 

Despite the fact that virtually every systematic review of the content and

impact of drug advertising confirms that it is of dubious information value,3,4

the financial gains from permitting advertising have proved too strong for

associations and their journals to resist. Through medical associations, drug

companies fund continuing medical education programmes, consensus conferences,

scientific meetings and prescribing guideline development. As economic theory

would predict, the result is educational events that systematically favour the

sponsor's products.8,9

 

Not only do firms influence the process by which evidence is disseminated –

putting their 'spin' on whatever the findings may be – they also influence how

the evidence is created in the first place. If investment in clinical sciences

can be orchestrated in a way that generates favourable findings – which, in

turn, generate more sales – economic theory predicts that firms will so

orchestrate their investments. And indeed, using financial, contractual and

legal means, drug manufacturers retain a degree of control over clinical

research far greater than most people realise.

 

The most obvious mechanisms through which the evidence can be biased occur in

drug trials sponsored by corporations.10 Trial sponsors commonly control the

research question, selection of patients, and other means to control the

evaluation. Combined, these have documented effects on empirical findings.

Clinical trials funded by drug companies are more likely than non-industry

funded trials to generate 'scientific evidence' that favours the funding

company's product, and the data is more favourably interpreted by those with

financial ties to related drug companies.11

 

Drug companies are also very careful about what aspects of their studies reach

the public domain.12,13 Since the clinical data generated by industry-funded

drug trials is proprietary, it is seldom open to competitive or public scrutiny.

Secrecy, however, is the antithesis of good, transparent science. It not only

undermines the external review processes for studies that are 'made public', but

it also engenders reporting biases because positive results are more likely to

get published and are frequently published multiple times.13-15 The evidence put

before the public is far rosier than the actual experiences of test subjects

would suggest.

 

Hospitals and universities have too often tacitly acquiesced to such practices

by permitting contract-based research on terms inimical to good science and

patients' interests.16 It should not be surprising, in a time of declining

public funding, that universities and hospitals are willing to accept research

contracts with strict disclosure and confidentiality clauses and/or

methodological flaws. Pharmaceutical companies are a major source of revenue

upon which hospitals and universities increasingly depend.

 

In addition to fees paid on contract for specific studies, drug companies give

large corporate grants to public institutions. These for-profit firms do not

engage in hand-outs without reasons tied, directly or indirectly, back to the

corporate bottom line. Gifts to public institutions from a drug company raises

that company's image and serves as a means through which it can influence the

decisions of universities and hospitals.

 

Even when drug companies are not the sponsors of research studies, they use

lawsuits and other means to influence what is studied and what is reported.

Legal threats, regardless of their merit, are increasingly being used as a means

by which the drug industry silences recalcitrant researchers.17-21 Lawsuits

significantly raise the anticipated costs of conducting and publishing clinical

research that yield results 'unfriendly' to the objectives of manufacturers.

 

Even if individual researchers under legal attack win in the courts, they lose

considerable time, energy and money, and are put at a disadvantage in research

competitions with their peers.17,20 Other researchers note this. It is hard to

gauge how much critical research is 'chilled' as a result, but such chilling is

a plausible company objective – 'punish one to teach a thousand'.

Evidence-biased medicine

Drug companies have also launched legal actions against those who conduct

independent evaluations and publish clinical guidelines.

 

In 1997, Bristol-Myers Squibb sought an injunction to prevent the Canadian

Coordinating Office of Health Technology Assessment (CCOHTA) from releasing a

summary report on drugs to lower blood cholesterol.

 

They were unsuccessful at trial, and on appeal, and received a judicial rebuke.

But they effectively shut down CCOHTA for a year and drained its budget.

Meanwhile they preserved their leading market position, generating revenues that

undoubtedly more than covered their legal expenses.

 

Increasingly, the industry is simply leaving the academics behind by having drug

trials designed, managed and reported by private, for-profit contract research

organisations. In 1991, academic centres accounted for 80 per cent of

industry-funded clinical trials; in 1998 they accounted for only 40 per

cent.22-24 Private research firms picked up the difference. The ostensible

reason for this change is that private firms can conduct research more quickly

than universities and hospitals. This is clearly of interest to firms who wish

to get the maximum number of market days out of their fixed-term patents.

 

But a second advantage of contract research is that the firm can retain complete

control over questions, methods, data and publications, without hindrance from

academic review processes. While academic researchers and clinicians may still

be involved, no individual will have sufficient grasp of the overall project to

be able to question methods or see warning signs in data coming in from all

participating centres.

 

Professional medical writers frequently write up the results of privately

contracted research. The articles are then published under the names of

prominent researchers or clinicians paid a fee for reviewing the manuscript and

attaching their names. The practice of ghost-written papers published under

'honorary' authorships has become so pervasive, and the belief that this reduces

accountability for research is so strong, that some medical journals now require

that authors list their contribution to the research.25

 

Using profit-making organisations to conduct research on behalf of drug

companies, and using public relations firms to put media 'spin' on the results

and coordinate their publication, completes the process by which the industry

has infiltrated every stage of the modern research enterprise. Faced with this

infiltration, patient welfare and scientific process are simply overwhelmed by

the profit objective of the pharmaceutical companies. Private practitioners have

become more-than-willing pawns in this process, often putting their own

financial and academic interests ahead of their patients' interests. In the

private, contract-based research setting, data gathering is conducted by

ordinary practising physicians.22-24 The fees paid for enlisting patients in

these studies, together with bonuses for meeting recruitment targets and

deadlines, can amount to hundreds of thousands of dollars a year.24 In this

context the notion of supplier-induced demand takes on a whole new complexion.

Inappropriate treatment occurring under heavy financial incentives appears to be

a form of 'collateral damage' acceptable to the doctors, contract research

organisations and funding drug companies.

 

Contract research for profit is a recent development, but all the other

marketing practices described above are decades old. Documentation of attempts

to generate biased clinical evidence for marketing purposes dates back decades.

As early as the mid-1950s, public commissions of inquiry in Canada, the US and

the UK all received testimonies of industry efforts to introduce bias into the

prescribing process, not only by the ubiquitous practice of giving gifts and

other benefits to prescribing physicians, but through financing articles in

journals intended for prescribing doctors, and influencing their content.26-28

 

Then, as now, drug companies: sponsored drug trials; hand-picked investigators

depending on the degree of quality needed (for example, picking young

investigators of little or no reputation to study the more dubious drugs);

discouraged the publication of unfavourable results; used multiple trials at

different centres to raise awareness of a drug before its market launch; and

published results multiple times (both before and after the drug's launch) so as

to hamper those searching for scientific evidence.

 

As Yale political scientist Ted Marmor has noted, 'Nothing that is regular is

stupid.' These practices are profitable.

References

1. Barer ML, McGrail KM et al (eds) (2000) Tales From the Other Drug Wars:

Proceedings from the 12th Annual Health Policy Conference. Centre for Health

Services and Policy Research, UBC. www.chspr.ubc.ca [26 September 2000]

 

2. Wazana A. (2000) Physicians and the pharmaceutical industry: Is a gift ever

just a gift? JAMA; 283 (3): 373–280.

 

3. Lexchin J. (1993) Interactions between physicians and the pharmaceutical

industry: what does the literature say? Can Med Assoc J; 149 (10): 1401–1407.

 

4. Guyatt G. (1994) Academic medicine and the pharmaceutical industry: a

cautionary tale. Can Med Assoc J; 150(6): 951-953.

 

5. Glassman PA et al (1999) Pharmaceutical advertising revenue and physician

organizations: how much is too much? Est J Med; 171 (4): 234–238.

 

6. Mabin DC. (1995) BMJ should declare its own conflict of interest. BMJ; 311:

878.

 

7. Ubel PA, et al (1995) Acceptance of external funds by physician

organizations: issues and policy options. J Gen Intern Med; 10: 624–630.

 

8. Sheldon TA, Smith GD. (1993) Consensus conferences as drug promotion. The

Lancet; 341 (8837): 100–103.

 

9. Spingarn RW, Berlin JA, Strom BL. (1996) When pharmaceutical manufacturers'

employees present grand rounds, what do residents remember? Acad Med; 71: 86–88.

 

10. Bero LA, Rennie D. (1996) Influences on the Quality of Public Drug Studies.

Int J Technol Assess Health Care; 12 (2): 209-237.

 

11. Brill-Edwards M. (2000) Canada's Health Protection Branch: Whose Health,

What Protection? In Tales From the Other Drug Wars: Proceedings from the 12th

Annual Health Policy Conference, Barer ML, McGrail KM et al. (eds.) Centre for

Health Services and Policy Research, UBC 2000; www.chspr.ubc.ca [26 September

2000]

 

12. Wahlbeck K, Adams C. (1999) Beyond conflict of interest: Sponsored drug

trials show more-favourable outcomes. BMJ; 318 (7181): 465.

 

13. Rosenberg SA. (1996) Secrecy in medical research. N Engl J Med; 334 (6):

392–4.

 

14. Rennie D. (1999) Fair conduct and fair reporting of clinical trials. JAMA;

282 (18): 1766-1768.

 

15. Johansen HK, Gotxche PC. (1999) Problems in the design and reporting of

trials of antifungal agents encountered during meta-analysis. JAMA; 282 (18):

1752–1759.

 

16. Angell M. (2000) Is academic medicine for sale? N Engl J Med; 342 (20):

1516-1518.

 

17. Shuchman M. (2000) Consequences of blowing the whistle in medical research.

Ann Intern Med; 132 (12): 1013–1014

 

18. Hemminiki E, Hailey D, Koivusalo M. (1999) The courts – a challenge to

health technology assessment. Science; 285 (5425): 203–204.

 

19. Hailey D. (2000) Scientific harassment by pharmaceutical companies: time to

stop. Can Med Assoc J; 162 (2): 212–213.

 

20. Evans RG. (2000) Uses and abuses of research and the research process. In

Barer ML, McGrail KM et al. (eds) Tales From the Other Drug Wars: Proceedings

from the 12th Annual Health Policy Conference. Centre for Health Services and

Policy Research, UBC 2000; www.chspr.ubc.ca [26 September 2000]

 

21. Rich P. (1999) Re-evaluating guidelines: clash between researcher and drug

company shows need for further clarification of the process. Medical Post; 25

(41): cover, 64.

 

22. Rettig R. (2000) The industrialization of clinical research. Health Affairs;

19 (2): 129–146.

 

23. Bodenheimer T. (2000) Uneasy alliance – clinical investigators and the

pharmaceutical industry. N Engl J Med; 342 (29): 1539.

 

24. Eichenwald K, Kolata G. (1999) Drug trials hide conflicts for doctors. New

York Times; May 16, 1999.

 

25. Rennie D, Flanagin A, Yank V. (2000) The contribution of authors. JAMA; 284

(1): 89–91.

 

26. Lang RW. (1974) The Politics of Drugs: A comparative pressure-group study of

the Canadian Pharmaceutical Manufacturers Association and the Association of the

British Pharmaceutical Industry. England: Saxon House.

 

27. Temin P. (1980) Taking Your Medicine: Drug Regulation in the United States.

Cambridge: Harvard University Press.

 

28. Restrictive Trade Practices Commission (1963) Report Concerning the

Manufacture, Distribution and Sale of Drugs. Ottawa: Queen's Printer.

 

Steve Morgan, Morris Barer and Robert Evans are academics at the Centre for

Health Services and Policy Research, University of British Columbia.

 

 

 

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