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The 1997 SMA Ethics Convention was held on 26 October 1997 at the College of Medicine Building. This was held in conjunction with the conferment of SMA Honorary Membership on Dr Kwa Soon Bee, and the 1997 SMA Lecture delivered by Dr Wong Heck Sing, which was reproduced in full in the November issue of the SMJ. The Keynote Address on “The Medical Profession and the Industry” was given by Professor Tan Siang Yong, Professor of Medicine and Adjunct Professor of Law, University of Hawaii Medical School. The Ethics Convention addressed two areas where ethical dilemmas abound: relationship with the pharmaceutical industry and Managed Care. The seminar on medical profession and the pharmaceutical industry is reported in this issue. The report on the Managed Care Seminar will be published in the January 1998 issue of the SMA News. 

Keynote address 
The medical profession and the pharmaceutical  industry are inseparable components of the medical ecosystem and exist in symbiosis. The onslaught of corporatised medicine in recent years threatens to erode this synergistic relationship and the moral fabric of the profession. Professor Tan Siang Yong addressed some of the ethical dilemmas which doctors may face in this milieu of market-driven forces in the keynote address. 

Pharmaceutical trade is lucrative business in the USA. The annual turnover of about 100 pharmaceutical companies in the US amounts to US$55 billion. Drug costs account for 8% of total health expenditure paid for mainly by patients themselves. It takes a company at least 12 years to put a drug on the market at an estimated cost of US$231 million per drug. For every 10,000 new applications to the USFDA for drug trials, about 20 enter animal trials, 10 enter human Phase 1 trials and only 1 finally gains approval for registration. It is evident therefore that the pharmaceutical industry takes high risks at high costs, but the pay-offs are enormous once a drug is registered for use. Prof Tan observed that it is only natural for pharmaceutical companies to strive to recoup their R & D costs and maximise the returns on their heavy investment before patent expiration in about 10 year’s time. 

To achieve their sales targets, pharmaceutical companies employ aggressive marketing strategies and spend up to US$10 billion a year on detailing, gifts and samples. Drug-sponsored CME is another promotion strategy and constitutes the major source of CME for doctors in the US. In 1988, 16 companies spent a total of US$200 million sponsoring 34,686 symposia. While such funding is essential for the majority of CMEs, a situation could arise whereby the theme of discussion revolves around the use of a particular drug manufactured by the sponsoring company. The organisers of the CME must have complete autonomy over the choice of topics and speakers. With increased collaboration between the academia and the industry, drug-sponsored research must be subjected to rigorous scientific scrutiny by neutral parties, and the researchers involved in the study must have no vested financial interest in the sponsoring company, or if they do, disclosure of such conflict of interest should be mandatory. Prof Tan advocated the “ABC” method for ethical analysis of any relationship between the medical profession and the industry - Appearance of impropriety; Benefit to patient; and Cost to patient. 

Looking into future trends in the next millenium, Prof Tan highlighted four main issues which need to be carefully evaluated. These are: direct marketing, generics, pharmacy benefit managers and the regulation of alternative medicine. 

There is an increasing trend towards direct marketing to patients by drug companies. In 1996, the industry spent US$600 million on direct marketing. Although this practice promotes healthy competition, educates the consumer and forces the doctor to keep up to date, drug advertisements could be misleading and generate unnecessary demand for new drugs which the consumer perceives as beneficial. 

The use of generics is increasing with US$15 billion being spent in 1995, compared to US$5.5 billion in 1991. Generics account for more than 60% of drugs prescribed and 80% of generics are manufactured by brand-name firms. The FDA approves about 200 generics each year while 1O pioneer drugs lose their patent protection annually. Although generics are cheaper than their brand-name counterparts, the rigorous quality control to ensure bioequivalence of within 20% of the patent drug may be absent. This could have significant clinical implications for drugs with narrow therapeutic window, such as psychotropic and anticonvulsant drugs. 

In recent years, Pharmacy Benefit Managers (PBM) have emerged to market drugs at cheap prices to HMOs in the USA. PBMs offer, in addition, services such as drug utilisation review, disease-state management protocols, patient compliance management, fomulary advice and CME programmes to their clients. Three of the largest PBMs in the US have been bought over by major pharmaceutical companies. PBMs provide clients with a cost effective prescribing mechanism through vertical integration. However, the use of PBMs tends to encourage a ‘cheque-book’  strategy and runs counter to fair competition from local companies. 

A New England Medical Journal article published in January 1993 observed that more Americans, especially the educated upper-income whites, are using alternative medicine than previously recognised. In 1990, Americans spent US$13.7 billion on alternative medicine. Such products include traditional Chinese medicine and ‘naturopathic’ products like melatonin, DHEA and Gingko. Proponents of alternative medicine assert that it is safe, effective and more holistic than Western medicine. The down side of alternative medicine is that it promotes quackery, exploits vulnerable patients and could even be dangerous and delays diagnosis and treatment of serious illnesses. 

The doctor as a client 
The roles of doctors and phamaceutical firms are in one sense complimentary. Such firms research and market new drugs, without which the therapeutic options available to doctors to combat disease will stagnate. However, if doctors do not support these new products, pharmaceutical firms cannot get any return on their investments, and will be forced to close. Unfortunately, while their roles may be complementary, the primary reasons for their existence differ fundamentally. Whatever their mission statements may say, pharmaceutical companies, like all other commercial company, exist primarily for profits. The management of the company is accountable to its shareholders in this manner. On the other hand, doctors practice medicine primarily to improve the health of their patients, with commercial considerations coming only a distant second. These differences may pose ethical considerations to doctors practising alone. 

Dr Lee Pheng Soon, pharmaceutical physician and GP, said that the prescribing habits of doctors tend to be modified by information provided to them by pharmaceutical companies. This may be in the form of advertisements in professional journals, product monographs, or even the content of verbal ‘sales-calls’. The SAPI Code states that regardless of the mode of transmission, any information provided to the doctor should be accurate, fair and objective. Claims should not be stronger than what scientific evidence warrants  and  every  effort  should  be  made  to  avoid ambiguity. However, it is in the company’s interest to present information about its products in the most favourable light possible. 

Dr Lee cited examples of unacceptable standard of promotion which he had observed over the years as a GP. 
1.  Incomplete information provided about the type of trial conducted. 
     Promotional material, quoting the results of a clinical trial, may not clearly state how far 
     the study design used falls short of the gold-standard in pharmaceutical medicine (ie. a 
     double-blind placebo controlled prospective randomised trial in an appropriate 
     sample). This omission is important, as sub-optional clinical trial design limits the 
     reliance that the doctor can place on the reported results. 
2.  Omission of the result of trials that do not support the drug. 
     Most advertising and promotional material only highlight results of positive trials. They 
     omit results of negative trials, and trials with competitor products that may be more 
     efficacious, or safer, or both. The predilection of medical journals to publish only the 
     results of clinical trials with positive results further compounds the information bias. 
3.  Inappropriate statistics. 
     Examples of misleading statistics include using graphs that do not have axes that start 
     from zero, using p-values calculated from one-tailed tests when the hypothesis is clearly 
     two-tailed, and using inappropriate statistical values, eg. using SE instead of SD. There 
     is also frequent failure to distinguish between ‘clinically significant’ and ‘statistically 
     significant’. Finally, one must also be wary of meta-analyses of convenience - pooling 
     non-compatable data and invalid cross comparisons to demonstrate superiority. 

Dr Lee advised doctors not to take product information at face value. They should question sales representatives intelligently on the basis of their claims of superiority and efficacy. Copies of the studies from which the data were drawn should be made available. He is certain that reputable pharmaceutical companies will welcome this sort of genuine interest, as it will give the more reputable companies the opportunity to distinguish themselves by their ethical promotional methods. Finally, doctors should not limit their source of drug information to what is provided by the pharmaceutical profession, but should attend CMEs and read journal updates as well, as these are more likely to provide information free of self-interest. 

The doctor as researcher-educator 
Doctors in institutional practice and the academia who are involved in research and education are in positions of leadership and influence and have the capability of shaping the opinions of other doctors, who are themselves potential prescribers. The researcher-educator interacts with the pharmaceutical profession in several ways, including: 
1.  Keeping up to date with research results from all available sources; 
2.  Evaluating new information on drugs; 
3.  Participating in clinical and non-clinical research; and 
4.  Teaching and informing the medical profession and the public of research results. 

There are possible ethical problems in each of these interactions. The likelihood of conflict of interest is real with the increase in the number of pharmaceutical companies funding research at all levels. Professor Lee Kok Onn of the National University Hospital highlighted the differences in the doctor-industry interaction in these areas between the USA and Europe, which could arise from differences in societal perception of the role of doctors in these countries. In the USA, the doctor is perceived as more of a consumer service provider while in Europe, he is accorded the role of the traditional healer, counsellor and patient-advocate, guided by an unseen divine hand. The perception of doctors in Singapore by the public lies in between the two. 

Doctors evaluating research in the USA are required to declare any conflict of interest. There are formal investigation channels and legal procedures to deal with fraudulent research in the USA while the situation in Europe and in Singapore is not that clear. ln Europe, publication rights lie with the doctor-researcher while in the USA, they are bound by contract. Direct lecturing to the public on pharmaceutical products by individual doctors is permissible in the USA but not in Europe or Singapore. 

Ultimately, doctors involved in research and teaching have to bear in mind that despite the possibility of conflict of interest, the patient’s welfare must come first and be the guiding principle in the conduct of any clinical research.