Pharmageddon (21 page)

Patient hopes and expectations work in favor of a pharmaceutical company bringing a new drug to the market, but in addition since the 1990s, doctors in many countries, whether they work for a health maintenance organization or in a universal healthcare system, have also had to adhere to drug formularies (lists of approved drugs) which dictate what they can and cannot prescribe. These formularies arose in response to perceptions that healthcare costs were escalating uncontrollably and that a key element in this escalation was the price of drugs. The formularies often start with a principle that, where possible, doctors should prescribe cheaper generic rather than higher cost, branded compounds. The guidelines are intended to be both evidence-based and cost-sensitive—with some trade offs, so that if a new drug costs more but could show a real benefit over older agents, for example, it would be included on the approved list. The types of assessments pharmacists and doctors with no links to industry would make in constructing formularies, it was thought, would in general slow the entry of unnecessary new drugs to the market.

When it came to managing costs, from the 1990s onward service managers and others could, at least in theory, also turn to health economics to assess company claims that their new drugs offered good value for the money. And of course if the market really was a free market and several different companies each brought to market new antihypertensives or treatments for osteoporosis, competition should drive the price of the new drugs down—as many from Senator Kevaufer in 1962 onward have argued.
⁵
But this has never happened.

In the fifteen years following the FDA ruling on Risperdal and other new antipsychotics, no independent evidence appeared that any of the newer antipsychotics was superior to the older ones in terms of either safety or efficacy—even though the new treatments cost between fifty and eighty times as much.
⁶
But in the interim the companies managed to convert virtually everyone in the medical community from older to newer antipsychotics, and all of the new drugs made it on to hospital formularies—how? More generally, how do the pharmaceutical companies manage to market newer drugs so successfully when the cost of healthcare is forcing everyone to be aware of costs and in the face of guidelines, which ostensibly based on the evidence might be expected to come to the same conclusion as the FDA?

Part of the answer to this conundrum lies in the medical academics who, as we have seen, are among the key people who influence a doctor's view of particular drugs. Regulators have no control over what these academics say—academics, often, whom pharmaceutical companies have made into opinion leaders. In the case of antipsychotics like Risperdal, statins like Lipitor, or proton pump inhibitors like Nexium, professors of medicine, psychiatry, pharmacology, or general practice can say what they like in lectures or report what they like in medical journals. Companies can even include statements in their ads claiming that, say, Risperdal is superior to haloperidol, provided it is clear the statement has been made by an academic rather than the company. There will be a footnote in the ad to a medical article in which superiority is claimed—almost certainly a ghostwritten article.

An even more effective marketing technique is to coax support from medical academics who are not hired guns, who may even see themselves as hostile to company marketing and keen to constrain this marketing within a framework of independent treatment guidelines. It is in fact by manipulating the most independent of medical academics through guidelines that companies have been able to make new drugs from Risperdal to Lipitor, Vioxx, Nexium, and Fosamax into the most profitable drugs in the world.

CONSENSUS CONFERENCES

In the 1980s it seemed obvious to many medical academics with no links to the pharmaceutical industry that where there was a dispute about a drug or other medical treatment it made sense to bring representatives of the differing points of view together in an attempt to achieve consensus. This led to the creation of consensus conferences aimed at producing guidelines for clinical practice.
⁷
Initially, these consensus conferences seemed like a way to rein in the excesses of pharmaceutical company marketing departments—if we review all the evidence it will surely be clear that the benefits of a new drug are far less than the marketing hype might suggest. With this in mind, groups across medicine began to convene conferences to produce treatment guidelines on new drugs for conditions ranging from arthritis to schizophrenia.

Initially, the organizers of these consensus conferences were in the business of developing guidance for doctors rather than guidelines to be rigidly adhered to. Twenty years later the guidelines we now have still notionally offer guidance to doctors, but this is the kind of help that once led Ronald Reagan to suggest that the scariest words in the English language were “I'm from the Government and I'm here to help you.”

By the time I was invited to a consensus conference in London convened by Catalyst Healthcare Communications on behalf of Janssen in 1995, drug companies far from feeling constrained by guidelines had begun to embrace them. Other invitees to this London meeting included senior psychiatrists, pharmacists, and economists. No one among the invitees would have been thought of as a friend of the pharmaceutical industry. We were presented with the published results of Janssen's trials of Risperdal. There was no attempt to stifle debate or to block us from bringing in any relevant material we might have been aware of.

The exercise involved taking the published research on Risperdal and discussing what would happen in real life if the results found in the clinical trials, which had all been reported in the better journals, applied. What effect would it likely have on the rate patients got discharged from acute hospital settings or from longer-term care facilities and on their rates of readmission to a hospital bed? When costing the outcomes, a significantly higher cost was used for Risperdal compared to the older drugs. Nevertheless, use of Risperdal came out as less expensive compared with older drugs in the long run. This result didn't make sense to me and was at odds with everything I saw about the use of Risperdal in clinical settings, where those taking Risperdal should have clearly been doing better if this “finding” was a real one.

Looking at how Catalyst pulled off this trick, it became clear that companies can almost guarantee an outcome like this. The reason: the bedrock on which guidelines depend is the published evidence from company clinical trials. If a guideline is going to be credible, its proposers should have access to all relevant trial data—exactly what the companies appeared to offer (but didn't). With this assumption, advocates of evidence-based medicine would think that, based on the data, the individual bias of participants or collective bias of the group or any bias stemming from the fact that these were company trials should have little effect on the final conclusions. A group of radiologists, doctors free of drug company influence, or even hostile to industry but prepared to go by the evidence, should come to much the same conclusion on Risperdal as our consensus group—that switching patients from older drugs to Risperdal would save money. This consensus-group meeting resulted in a publication claiming that treatment with Risperdal offered value for money.
⁸
It was followed over the next few years by publications on results from similar exercises undertaken with Zyprexa and other antipsychotics.
⁹

Slightly over a year later I was invited to another consensus conference, again linked to Janssen and Risperdal. The procedure was the same. We had all been sent a dossier with all the published Risperdal trials as well as trials of other new antipsychotics. Any other information we asked for was forthcoming. Based on this material, we were asked what would be the optimal and cost-effective first line of treatment for patients with schizophrenia in chronic care and other treatment settings. Again based on the clinical trial data, Risperdal looked good and “our findings” were presented under our names at major international psychopharmacology settings.
¹⁰

Pharmaco-economic evaluations like that of our consensus group were, at least on the surface, aimed at costing medical procedures to determine which offered value for money. A few voices at the time were saying that we in medicine couldn't do what the economists were purporting to do—that too little was understood about what really goes on in medical care. But it seemed clear the pharmaceutical industry was going to pull this new discipline into existence. Drugs function within healthcare the way automobiles do in the wider economy—they can be costed while the degradation of the environment or of medical care remains unmeasurable and uncostable.

Before getting involved in any of these consensus conferences, I had committed myself to the position that pharmaco-economics was bogus science in a debate over claims that the first of the new antipsychotics, Clozaril, which had been launched in 1989 with a price tag of roughly $10,000 per year compared with $100 for the older drugs, was nevertheless cost-effective.
¹¹
It was clear at the time that Clozaril had set a price benchmark that, if it did not meet significant resistance, would become the price norm for any subsequent new antipsychotics coming on the market, with major economic consequences for individual patients and health systems in general.

As part of company marketing strategies, economic evaluations of antidepressants also began to come onstream in the 1990s. These purported to show that despite a price of $1,000 per year for a drug like Prozac, compared with the $100 (or less) price tag for older drugs, the new drugs represented value for the money.
¹²
Along with colleagues, I had argued that such prices were even more likely to lead to serious adverse financial consequences for the health services than the even bigger markup on antipsychotics because so many more people were prescribed antidepressants.
¹³
This seemed obvious, but no one else was saying it. In the face of publications in leading journals claiming the SSRIs or other new treatments would produce savings, there was no dissent.

Given my published positions, it is interesting that company personnel felt confident asking me along to a meeting on economic evaluations and consensus guidelines. Ironically, a few years later, when an independent expert for Britain's National Institute for Health and Clinical Excellence (NICE) suggested consulting me on the antidepressant guidelines NICE were constructing, the idea was shot down on the basis that Healy was too anticorporate when it came to drugs. Too anti-drug-company for NICE, but just perfect, it seems, for pharmaceutical companies.

Why go to meetings like this? It paid. For many outside observers, the repeated endorsement of on-patent products over older drugs at guideline meetings is close to inexplicable. Finding that the participants at these meetings have at some time been paid by a pharmaceutical company seems the only way to account for this. How else can you explain, for instance, the fact that in these guidelines Healy seems to be endorsing things when he has in other places appeared to say the opposite?

Another factor is lots of us want to be where the action is and industry is very good at creating action or at least the appearance of action. A further factor is friendship. Put in rooms for meetings like these, even people who have been on the opposite sides of arguments in print tend to get on. If others seem friendly in the flesh, it's somehow easier to see where they're coming from or to find a way to reconcile views. Companies excel at cultivating friendships—remembering details about you and making you feel that you count. Besides, as the taint of working with industry has receded and as more and more people are linked in, there increasingly seem to be fewer and fewer differences between “them” and “us.” This is a world in which conflict of interest becomes a badge of honor, the more links to the greater number of companies the better.

These are all important issues but the conflicting interests of payment, friendship, or boredom do not explain what happens. Here's a further puzzle—the guidelines emanating from company-sponsored meetings are all but indistinguishable from those produced by committees with no links to the pharmaceutical industry. Whether the game is played by free market rules or within a socialized system, industry wins.

ONE GUIDELINE, ONE VOICE

To bring out how companies manage to win regardless of which way the game is played, let us contrast practices in the United States and Britain, in particular the operations of the British guideline system run by the National Institute for Health and Clinical Excellence (NICE), widely regarded as the most independent guideline system in the world, and the American Texas Medication Algorithm Project (TMAP).
¹⁴
TMAP was created by industry. NICE was set up in part to contain industry and has the distinction of having been sued by companies for advising against current drug treatments for Alzheimer's disease. NICE is exactly the kind of system that the Obama administration looked to put in place as part of its healthcare reform package.
¹⁵

TMAP was set up in 1994, the year after Risperdal was launched in the United States. The project was initially funded by Janssen but soon thereafter all of the other major pharmaceutical companies had signed on as well. TMAP started with a panel of experts convened to produce a consensus on the use of antipsychotics. Later panels were pulled together to consider the use of antidepressants and mood stabilizers. Many of these consultants had prior links to Janssen and other companies operating in the mental health field, but these experts were distinguished psychiatrists and psychopharmacologists, and none have complained about having data withheld from them.

The first set of TMAP guidelines concluded that the recently launched antipsychotics—Risperdal, Zyprexa, and Seroquel—were the drugs of choice for schizophrenia. A second set of guidelines concluded that rather than older, cheaper antidepressants, the more recently launched on-patent Prozac, Paxil, and Zoloft were now the drugs of choice for depression. Further guidelines moved on to endorse mood stabilizers such as Depakote over other treatments for bipolar disorder. In each case the guidelines recommended newer drugs as safer, more effective, and better tolerated than older agents. In 1999 TMAP commissioned a set of guidelines for the management of childhood mental disorders, even though at the time no psychotropic drugs had been licensed for use in children or teenagers.
¹⁶