There is no doubting that in recent times, the pharmaceutical industry has been met with growing scepticism and outright mistrust from many quarters. This is primarily in relation to the controversy surrounding many drug companies' decision to withhold negative clinical trial data from public scrutiny. The practice of non-disclosure relating to such negative findings leads to erroneously exaggerated claims of efficacy or minimised reports of harm in relation to a drug. In the UK, the All Trials Initiative is spearheading the lobbying of government, regulators and research bodies to impose mandatory disclosure of all clinical trial data. But what if these initiatives actually succeeded in achieving their goals? Would this really signify an absolute victory over the pharmaceutical industry's use of deceptive tactics to mislead doctors and patients alike? Or do they have other ways and means of manipulation?
I fear there is another facet in the industry's armamentarium which has hitherto been relatively neglected in the shadow of clinical trial disclosure-welcome to the world of drug promotion. After all, even if a drug company was compelled to publish all its data pertaining to a particular medication, why would this necessarily prevent them from going on to market their product by selectively minimising (or even omitting) the negative findings, whilst simultaneously exaggerating the positive ones?
In a landmark case in 2012, Johnson and Johnson were fined $1.1 billion after a court ruled that the company misled doctors over the risks associated with the antipsychotic drug risperidone. It declared that the company engaged in ‘false or deceptive’ acts in 2003, when it sent a letter to 6000 doctors claiming that it was safer than its rivals .
A study published in the Lancet suggested that misleading drug advertising aimed at prescribers was a widespread phenomenon . A researcher in Spain reviewed over one hundred advertisements for blood pressure and cholesterol drugs published in medical journals, and found that 44% made claims which were not backed by evidence. Similarly, Dutch researchers analysing the world's leading medical journals found that only half of the claims in adverts were supported by the trials that the adverts themselves referenced, and less than half referenced high-quality trials to substantiate their claims . Indeed, the most exhaustive systematic review assessing drug advertisements found that a third did not contain claims supported by a randomised controlled trial, a systematic review or meta-analysis .
In the UK, in 2005, the MHRA (Medicines and Healthcare Products Regulatory Agency) reported that it planned to ‘name and shame’ companies which engage in poor practice with respect to producing misleading promotional material . It claimed that it would clamp down on companies whose adverts used inflated claims or confusing information. Professor Kent Woods, Chief Executive of the MHRA stated, ‘the key principle behind the guidelines is that they must protect the public, by preventing people from being mislead by poor advertising.’ However, the authority has been accused of weak regulation. The Consumer's Association accused the MHRA of failing to adequately police the pharmaceutical industry after three adverts were withdrawn from medical journals in 1 year following investigations by their publication, Drug and Therapeutics Bulletin. The Consumer Association's principal policy advisor commented, ‘the fact that yet another advert has had to be withdrawn not only calls into question the ability of the MHRA to do it's job, but highlights the fact that drug companies are incapable of communicating honesty with healthcare professionals, let alone the public.' The editor of the Drug and Therapeutics Bulletin further added, ‘there appears to be an epidemic of misleading advertising.’ Thus, it would appear that the pharmaceutical industry is not sufficiently concerned by the regulatory body's warnings if they are found to be using misleading advertising, and are free to capitalise on weak regulation. Clearly, the requirement that such promotions are rectified with immediate effect and the associated negative publicity are not sufficient deterrents for the companies to change their behaviours. Unfortunately, the UK Department of Health has refused to insist that drug companies who make false claims are forced to issue statements of correction in their advertisements . This appears that until the authorities are able to take much more aggressive and punitive action against drug companies, they will continue to take their chances and act with apparent impunity.
Misleading advertising is an even bigger problem in the US, where drug companies are permitted to advertise their products ‘direct to the consumer’. Prior to the late 1990s, drugs were seldom advertised on television because regulators required exhaustive details including all potential side effects, no matter how rare. However, the FDA relaxed these regulations in 1997, opening the floodgates to overhyped marketing. Spending on drug advertisements aimed at consumers skyrocketed, from a mere $844 million in 1997, to $2.2 billion by 2000 . It was clear that the FDA had relaxed its stance on regulating the drug companies promotion of their products to consumers, issuing only 21 ‘warning letters’ in 2006 (as compared with 142 in 1997) . Most drug companies circumvented the less onerous side effect rules by simply listing them in extremely rapid scrolling sequence in tiny print at the very end of the promotion.
Keen to make amends, the FDA had made serious attempts to curb the practice in the US, where its Office of Prescription Drug Promotion (OPDP) launched the ‘BadAd’ campaign on the 11th of May 2010. This is ‘an outreach program designed to educate healthcare providers about the role they can play in helping the agency make sure that prescription drug advertising and promotion is truthful and not misleading.’ It encourages healthcare professionals to report possible instances of such activities. Unfortunately, despite the FDA's tougher stance on dealing with inaccurate, unbalanced or otherwise misleading drug promotions, the industry is still willing to chance its arm. This was exemplified by another ‘warning letter’ issued to Pfizer in July 2011 (FDA 2010–2011 BadAd annual report). The letter notified the company of misrepresentations regarding three of its medications which were advertised on a Lipitor (trade name for Atorvastatin) webpage link. The FDA reported that in all three cases, no risk information was provided. This was most alarming in the case of Chantix, its smoking cessation drug, which carries a black box warning (the most serious alert) on its packaging relating to suicidality. Fortunately for us in the EU, such overt deceptive tactics through ‘direct to consumer’ advertising are not a concern, as legislation outlaws this practice.
Another tactic employed by drug companies in advertising campaigns is to change the basis of a condition in a way which aligns it to their product's particular actions. A prime example of this practice is observed in the marketing of the selective serotonin reuptake inhibitor (SSRI) antidepressants. The so-called ‘chemical imbalance’ theory of depression, primarily relating to a deficiency in serotonin, has long been recognised as a gross oversimplification of the mechanisms underpinning clinical depression. Despite this, the theory is very convenient and exploitable for those companies selling drugs which increase serotonin levels. After all, most depressed individuals would prefer to believe that their misery is attributable to a simple chemical imbalance which can be restored to normal by simply taking a pill everyday. It is postulated that anxious and depressed patients, like other vulnerable groups, ‘are probably more susceptible to the controlling influence of advertisements.’ That is to say, they are highly suggestible, and are thus at risk of falling under the spell of the seductive drug advert . In a sense, it absolves them of any responsibility for maintaining their illness, and implies that lifestyle changes, talking therapies and drugs which act via different mechanisms are all useless. Those who are convinced that they are suffering from a neurotransmitter deficit have been shown to be more likely to request antidepressants, and to be sceptical of doctors who suggest alternative treatment modalities such as CBT . And so, drug companies are keen to perpetuate this erroneous notion as it makes their drugs seem like the simple answer to the simple problem of chemical imbalance. And so, we have adverts for sertraline stating, ‘scientists believe that depression could be linked with an imbalance of a chemical called serotonin’ , and for paroxetine, ‘with continued treatment, paroxetine can help restore the balance of serotonin’ . There are no references to the limitations of the serotonin hypothesis in these advertisements. And despite protestations, the FDA has never cited a drug company for this type of misleading advertising. Several studies have demonstrated the impact of such adverts on prescribing. One such study employed trained actors to present to their physicians with symptoms of depression, and then to act in one of three ways: to request a specific antidepressant, to request an unspecified medication, or to make no request. The outcome: patients usually get what they ask for, and this is exactly the effect advertisements strive to achieve. Furthermore, the same actors presented with an adjustment disorder, half of those who requested a specific drug got a prescription for it, even when it may not have been clinically indicated .
This tactic is part of a wider covert ploy known as ‘disease mongering’, or ‘medicalisation’, whereby conditions are altered (as exemplified above), given greater prominence or are broadened in concept, usually with the motivation of driving up sales of a newly available drug or drug indication. Ray Moynihan and colleagues, writing in the BMJ, described disease mongering as, ‘widening the boundaries of treatable illness in order to expand markets for those who sell and deliver treatments’ . The SSRIs once again make a good case in point. At present, these medications have licensed indications not only for depression, but also for generalised anxiety disorder, social phobia, OCD, premenstrual dysphoric disorder, panic disorder, PTSD and bulimia nervosa. Whilst there is good evidence that these drugs are effective treatments for such a heterogeneous range of conditions, there is little doubt that drug sales have benefited from increased public awareness of these illnesses at the hands of the pharma industry. The US National Comorbidity Survey of 1998 estimated that more than 13% of Americans experience the symptoms of social phobia at some point in their lives, and that 4.5% of the population meets the diagnostic criteria at any given point . Based on these figures, the study concluded that social phobia was the third most common mental disorder in the US, after depression and alcoholism. In 1999, paroxetine became licensed for the treatment of social phobia, and GSK launched a $90 million campaign to ‘raise awareness’ of the condition: ‘imagine being allergic to people’, the tagline read. It is a very clever form of indirect drug promotion: if you raise awareness of a condition, you raise awareness of a pill to cure it. Of course, the dangers of this practice are clear: many people will end up being labelled with conditions they may not have (at least not to a clinical degree), and end up on medication which they may not need (in addition to exposing them to unnecessary iatrogenic harm). The same malevolent forces were recognised to be influencing the promotion of Prozac to treat Premenstrual Dysphoric Disorder, when in 2003, the Committee for Proprietary Medicinal Products removed the license for this indication, stating ‘PMDD is not a well-established disease entity across Europe …. There was considerable concern that women with less severe premenstrual symptoms might erroneously receive a diagnosis of PMDD resulting in widespread inappropriate short and long-term use of fluoxetine’ . This growing trend for medicalisation or labelling of dubious nosological entities is gathering pace at an alarming rate, and as the publication of the American Psychiatric Association's DSM-5 looms large, we wait with baited breath for treatment guidelines for conditions such as ‘Temper Dysregulation Disorder with Dysphoria’, and ‘Slow Cognitive Tempo Disorder’.
Sometimes, drug companies will up the ante even further, going from ‘disease mongering’ to downright ‘scare mongering.’ In 2003, Pfizer, the manufacturer of Lipitor (atorvastatin), ran a campaign with print adverts that used images of a tagged toe of a corpse, with the tagline ‘which would you rather have, a cholesterol test or a final exam’. On television, they depicted a young, healthy man dying suddenly of a heart attack, leaving his family grief-stricken. These adverts strongly implied that cholesterol testing and treatment could prevent premature death from heart attacks in healthy people, contrary to the prevailing evidence at the time .
There are some who may contest that pharmaceutical companies are businesses just like any other, and as such, they use perfectly legitimate marketing techniques to boost sales of their products. All companies promote their products in such a way as to maximise profits, after all. From this perspective, the pharma industry is no more guilty than any other business stream. Their function is to make money, after all, the industry is estimated to be worth $600 billion per annum.
So what of other, more covert, techniques drug companies may utilise to encourage doctors to prescribe their products over the competition. The use of ‘drug representatives’ is a long-established method of covert influence. This tactic clearly works, as evidenced by the fact that at least half of a drug company's promotional budget is spent on paying drug representatives. A philosophy of targeting the doctors of the future seems to be prevalent in this world, with the vast majority of medical students reporting having some contact with drug representatives before they qualify . One may assume that doctors are impervious to the influential effect of contact with drug reps, and that such interactions wouldn't affect the prescribing practice of professionals who are supposed to follow robust, impartial, evidence-based work. Sadly, the research in this area tends to suggest otherwise. A recent systematic review revealed that almost 60% of the studies scrutinised found that doctors who have regular contact with drug representatives are more likely to prescribe their medication, and that they are more prone to divert from best-practice guidelines . And exposure to drug representatives is virtually unavoidable in clinical practice, even if you make a concerted effort not to consort with them. In reality, most doctors would agree that drug representatives have an almost omnipresent power. Even if you decline a personal meeting with a representative, you will encounter them and their promotional paraphernalia at the vast majority of teaching events, be it local, regional, national or international. The majority of CPD events are drug-company sponsored, with lavish meals in fashionable eateries. As long as there is some ‘educational content’ along the way, these are all perfectly legitimate tactics regularly deployed to charm and ingratiate doctors. Indeed, the hospitality offered by drug companies for sponsored ‘educational’ events are unregulated. And so, we are treated to conferences held in posh hotels, with free accommodation, food and even alcohol. Many doctors would find such offers too tempting to turn down, even if they have no interest in the drug being promoted. And the evidence suggests that drug representatives leave quite an impressionable mark, particularly on the newly qualified naive ones . Indeed, in 2011, the Serious Fraud Office declared that it would be investigating corporate entertainment for NHS staff, which it felt went beyond ‘sensible proportionate promotional expenditure’ .
And then there are always the indirect, covert ways of planting a particular drug's name in your head-the pens, the mugs, the sticky notepads, the flash drives and on the list goes. How can repeated exposure to a drug logo on a pen or mug we use many times every day not have some subconscious influence on our prescribing practice. Repeated exposure is a well-established and proven marketing technique.
Other covert tactics of influence exist in the domain of academia. A technique employed by drug company sponsored research articles, reviews and editorials is to assign an acclaimed or influential ‘expert’ in a particular field as the lead author, when, in fact, they may have had little (or nothing) to do with the piece of literature. They are known as ‘ghost authors.’ This is obviously a mutually beneficial arrangement symbiosis at its finest! The drug company gets the credibility of a well-renowned expert backing their claims, and the expert accrues an ever-expanding list of articles to their name. Of course, it is nigh on impossible to quantify exactly how widespread this practice is. However, a landmark study published in the BMJ in 2011, which analysed almost 900 articles from the six leading medical journals, revealed that 8% of the two-thirds of articles who responded, admitted to using ghost authors . This figure, although alarming in itself, is likely to be a massive underestimation of the true extent of the practice.
In conclusion, pharmaceutical companies are well-oiled business machines, which employ a variety of tactics to promote or influence the uptake of their products. These vary from misleading advertising to charm offences to repeated exposure to ‘doctored’ research articles. Their armamentarium of techniques is broad and sophisticated. The only way to counter such business tactics is to increase awareness of tactics employed, and to maintain a healthy dose of scepticism and vigilance. Caveat emptor!