Peter R Mansfield

Information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing: A systematic review

Geoff Spurling and colleagues report findings of a systematic review looking at the relationship between exposure to promotional material from pharmaceutical companies and the quality, quantity, and cost of prescribing. They fail to find evidence of improvements in prescribing after exposure, and find some evidence of an association with higher prescribing frequency, higher costs, or lower prescribing quality.

What Are the Public Health Effects of Direct-to-Consumer Drug Advertising?

Background to the debate: Only two industrialized countries, the United States and New Zealand, allow direct-to-consumer advertising (DTCA) of prescription medicines, although New Zealand is planning a ban [ 1]. The challenge for these governments is ensuring that DTCA is more beneficial than harmful. Proponents of DTCA argue that it helps to inform the public about available treatments and stimulates appropriate use of drugs for high-priority illnesses (such as statin use in people with ischemic heart disease). Critics argue that the information in the adverts is often biased and misleading, and that DTCA raises prescribing costs without net evidence of health benefits.

Single-Enantiomer Drugs Elegant Science, Disappointing Effects

Most new drugs are marketed as single enantiomers but many older agents are still available in racemic form. As these drugs reach the end of their patent life manufacturers become interested in marketing single enantiomer equivalents. This is called ‘chiral switching’ and it has been claimed that it will bring clinical benefits in terms of improved efficacy, more predictable pharmacokinetics or reduced toxicity. We reviewed the clinical evidence and prices for three recently marketed single enantiomer versions of widely used racemic drugs: escitalopram, esomeprazole and levosalbutamol. Claims of increased efficacy were based on comparisons of non-equivalent doses and any advantages seemed small and clinically unimportant. Prices of esomeprazole and levosalbutamol were higher than their racemic alternatives and we predict that these prices will remain high despite the market presence of generic versions of the racemates. Patent protection and a perception of superiority based on promotion rather than evidence will maintian price premiums for single enantiomer drugs that are not justified on the basis of clinical performance.

Educating Health Professionals about Drug and Device Promotion: Advocates' Recommendations

Mansfield and colleagues outline the recommendations from four advocacy groups for improving the education of health professionals on promotion of drugs and devices.

Drug companies' evidence to justify advertising

Ten international pharmaceutical companies were asked by letter to supply their best evidence in support of marketing claims for seventeen products. Fifteen replies were received. Seven replies cited a total of 67 references: 31 contained relevant original data and only 13 were controlled trials, all of which had serious methodological flaws. There were four reports of changes in advertising claims and one company ceased marketing nikethamide in the third world. Standards of evidence used to justify advertising claims are inadequate.

Escitalopram: Superior to Citalopram or a Chiral Chimera?

Background: Escitalopram is the active isomer of the antidepressant citalopram. In theory single-isomer drugs may be superior but few have been found to have clinically significant advantages. The manufacturer claims that escitalopram has more efficacy and a faster onset of effect than citalopram. The purpose of this study was to assess how far these claims are justified. Methods: Relevant trial reports were requested from H. Lundbeck A/S and the Swedish drug regulatory authority. The trials consisted of a pooled analysis of 1,321 patients from one unpublished, one partly published and one published eight-week trial, as well as a 24-week trial with 357 patients published as a poster. The studies compared escitalopram with placebo and/or citalopram in outpatients aged ≧18 years who met specified criteria for depression. The trials’ quality was assessed with Moncrieff et al.’s quality assessment instrument and the results compared with the claims from the advertisements. Results: The advertising claims are not justified because they are based on secondary outcomes, non-intention-to-treat analyses and arbitrarily defined subgroups. The subgroup results are inconsistent. Methodological flaws in the trials could account for the differences found. Even if the differences claimed were real they appear too small to justify higher prices. Conclusions: On the evidence available to us the manufacturer’s claims of superiority for escitalopram over citalopram are unwarranted. The Swedish and Danish drug regulatory authorities reached similar conclusions. This highlights the need for wider dissemination of national authorities’ statements to other countries affected by the European Union’s mutual recognition procedure.

Banning all drug promotion is the best option pending major reforms

Drug promotion should be evaluated according to its impact on health, access to information, informed consent, and wealth. Drug promotion currently does more harm than good to each of these objectives because it is usually misleading. This is a systemic problem. Whilst improved regulation and education will address it to some degree, major reforms to payment systems for drug companies and doctors are also required. Until all these systemic reforms can be put in place, the best policy option is to ban the promotion of drugs to doctors and the public. Consequently, pending major reforms, it is appropriate for governments to restrict drug promotion as much as is politically achievable.

General practitioners and pharmaceutical sales representatives: quality improvement research.

Background and objective: Interaction between pharmaceutical sales representatives (PSRs) and general practitioners (GPs) may have an adverse impact on GP prescribing and therefore may be ethically questionable. This study aimed to evaluate the interactions between PSRs and GPs in an Australian general practice, and develop and evaluate a policy to guide the interaction. Methods: Doctors’ prescribing, diaries, practice promotional material and samples were audited and a staff survey undertaken. After receiving feedback, the staff voted on practice policy options. The resulting policy was evaluated 3 and 9 months. Results: Prior to the intervention, GPs spent on average 40 min/doctor/month with PSRs. There were 239 items of promotional material in the practice and 4660 tablets in the sample cupboard. These were reduced by 32% and 59%, respectively, at 3 months after policy adoption and the reduction was sustained at 9 months. Vioxx was the most common drug name in promotional material. Staff adopted a policy of reduced access to PSRs including: reception staff not to make appointments for PSRs or accept promotional material; PSRs cannot access sample cupboards; GPs wishing to see PSRs may do so outside consulting hours. At 3 and 9 months, most staff were satisfied with the changes. Promotional items/room were not significantly reduced at 3 months (−4.0 items/room ; 95% CI −6.61 to −1.39; p = 0.066) or 9 months (−2.63 items/room; 95% CI −5.86 to 0.60; p = 0.24). Generic prescribing significantly increased at 3 months (OR 2.28, 95% CI 1.31 to 3.86; p = 0.0027) and 9 months (OR 2.07, 95% CI 1.13 to 3.82; p = 0.016). Conclusion: There was a marked reduction in interactions with PSRs with majority staff satisfaction and improved prescribing practices. The new policy will form part of the practice’s orientation package. Reception staff give PSRs a letter explaining the policy. It is hoped that the extra 40 min/doctor of consulting time translates into more time with patients and time to evaluate more independent sources of drug information.

Bribes for Doctors: A Gift for Bioethicists?

Research, teaching, and debate about gifts from drug companies to doctors might give bioethicists the greatest opportunity to help improve healthcare during the twentyarst century. My organization, Healthy Skepticism, has been campaigning for 20 years to improve health by reducing harm from misleading promotion (see http:// www.healthyskepticism.com). We have identiaed gifts as a key factor in the widespread dependence of doctors on information from drug companies. That information is often misleading. Consequently the article by Dana Katz, Arthur Caplan, and Jon Merz (2003) about gifts is extremely important. They have produced an excellent summary of the evidence that all gifts, both large and small, are a major cause of harm. One of the many strengths of their article is the use of insights from psychology to understand how the use of conscious and subconscious reciprocal obligation can manipulate doctors. I will provide four additional considerations and then speculate about how medical students and doctors think about gifts. Finally I will attempt some constructive suggestions about how bioethicists can help advance this issue.

Industry-Sponsored Research: A More Comprehensive Alternative

Julio Sotelos proposal for pharmaceutical research to be organised by a Collegiate Research Council (CRC) funded by drug companies [1] is one of several alternatives that deserve debate [2]. The Sotelo proposal has advantages, but if the CRC is a single international monopoly how could the risk of corruption and inefficiency be managed? Alternatively, if there were competing CRCs, they would be under pressure to compromise to win more contracts, as happens already with contract research organisations. Fiona Godlee has proposed that pharmaceutical manufacturers be banned from researching their products [3]. She suggests that “to get their products licensed [drug companies] would contribute to a central pot for independent, publicly funded clinical trials.” She did not specify what percentage of the “central pot” would be funded by taxpayers versus pharmaceutical companies. If the funding was mostly from pharmaceutical companies then her proposal is similar to Sotelos. If not, how will governments to be persuaded to allocate adequate funds? My organisation, Healthy Skepticism Inc., advocates a more comprehensive alternative that will also reduce the harms currently caused by misleading promotion, biased industry funding of education, and high drug prices. Our alternative is politically achievable because implementation can be achieved without increasing costs for pharmaceuticals currently paid by individuals and/or third party payers (governments or insurance companies) whilst securing long-term competitive return on investment for the pharmaceutical industry. Pharmaceutical companies currently have four main functions: manufacturing, research, promotion, and education. Performance of those functions is currently distorted by incentive systems that reward only activities that increase sales of more expensive drugs regardless of the impact on health care. We recommend that these four functions be paid for separately by government agencies via iterative open competitive public tender. This would allow the relevant divisions and subcontractors of pharmaceutical companies to compete with universities and other non-profit organisations for funding to provide each function separately. Incentives can then to be aligned to reward quality performance at each function separately. If a company performed poorly, e.g., committed research fraud or provided misleading promotion, then it would not get funding for that function in the next tender round. Drug prices would no longer include a premium for research, promotion, and education. Consequently, drug companies would no longer fund those functions from drug sales. Lower prices would make drugs more cost-effective for larger numbers of people. Our recommendations can be implemented quickly or slowly by gradually reducing prices and transferring the savings to organisations that fund research (e.g., the United Kingdom Medical Research Council); education (e.g., medical schools and specialist colleges); and promotion (e.g., Best Practice Advocacy Centre, New Zealand). We also recommend improving regulation of pharmaceutical companies and improving education, incentive systems, and regulation for health professionals[4–7].