Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugsis a warm, humorous, and insightful book by Jerry Avorn about three questions: Which medicines work? What side effects and risks do they have? And how much should we pay for them?
Important as medicines are, many of Avorn's observations and suggestions generalize to other fields. Coming to acceptable tradeoffs between risks, benefits, and costs - especially when the discussion is distorted by those with self-interested agendas - is a key social technology for which this book offers practical insights.
Jerry Avorn's desire to improve the prescription drug infrastructure is clear, yet he builds his case carefully - advancing step by step with the reader toward understanding where the scientific and human challenges lie, why they exist, and what can be done about them.
For most of history, accurate medicinal knowledge was rare, except for the most obvious cases - intoxicants for dulling pain, poisonous mushrooms, that sort of thing. We're just not good at judging causality or probabilities without the scaffolding of statistics and controlled experiments.
Two great innovations helped overcome this. The first was careful epidemiological studies, as with 19th-century pioneer John Snow mapping cholera outbreaks to trace back the causal factors. The second was the randomized trial, which assigned putative treatments to different groups and used statistics to measure the results for significance.
Unfortunately, in the real world, the benefit of drugs can be very difficult to judge accurately. Randomized trials have limitations such as budget constraints, time, and the difficulty of accurately replicating the target population. And even given a large, well-funded randomized trial, there is the complexity of observational inference to contend with - drugs can have subtle or long-term effects that can be difficult to understand.
So one complementary avenue is to try pharmacoepidemiology - observe the effects of a drug in the wild (i.e. patients), and make inferences from the messy real world with all its confounding factors. This gives a much larger patient population with which to infer data than a randomized trial, and as a bonus the study of patient data can unearth correlations with pre-existing conditions, differences in treatment methods, the effect of economic and insurance policies, and so forth.
Suppose that all these hurdles are overcome, and you understand the benefits of a drug. You still must understand the risks that come with the benefits, which brings up another set of problems. For example, how can differing risks be compared? Is a 1 in 100000 chance of death worse than a 1 in 10 chance of severe nausea?
Of course, all these difficulties become greatly compounded when some profit-driven drug companies make exaggerated claims for medications, or use any of a host of methods to skew the informational landscape in favor of their products:
At the beginning of the twenty-first century, many find it pathetically retro to warn of the dangers of unlimited corporate freedom. But just as the last century proved the ineptitude of planned economies and excessive government intervention, we now risk demonstrating the opposite: the downsides of unfettered corporate license, and the risks of inadequate public oversight of markets. For many sectors of the economy, such as computers, clothing, food, and automobiles, the marketplace works reasonably well with only modest regulation. For others, like housing, energy, and telecommunications, history teaches us that more governmental oversight is essential. And for one key component of society, the delivery of health care, we are finding that a laissez-faire marketplace approach hasn't worked well at all...Despite the overwhelming sway that profit-driven models presently hold over policy discourse, we need to recall that useful human behavior can spring from other sources as well.
Avorn lists some hypothetical conditions that would be required for marketing drugs directly to consumers to yield acceptable outcomes, such as customers being able to judge the quality of the product and do a rough cost-benefit analysis. These conditions are rarely satisfied in practice. He then goes on to tackle a tough question: how much is an increase in health worth?
...It doesn't help for us to declare that human health is too precious to place a dollar value on, or that the government should just lower drug prices, or that all medication costs, however high they are, should simply be paid for by somebody. Even in countries with strict drug price controls, even when lower-cost generics are used whenever possible, these choices still force themselves upon us.
...One early attempt to measure the benefits that come from medications and other health care interventions was based on the notion of 'human capital', and flowed directly from industrial cost-benefit analyses. A decision on whether to repair a machine or retool a factory would start by calculating the future productivity expected from the equipment, given its age and condition...We've all confronted this kind of choice with our cars or refrigerators or computers, though usually not with our grandmothers."
He then goes on to disparage short-sighted "net livelihood" econometric analysis that values a health policy primarily on its effect on the affected population's productivity - e.g. the infamous claim that "smoking is economically useful" since smokers die before needing expensive medical care or pensions, or prioritizing toxic waste cleanup by the income of people living in each area. Willingness to pay (calculating how much a person would be willing to spend for a given increment of risk or pain reduction) is also largely dismissed, not least due to its inaccuracy in practice.
So what's left? There isn't an easy solution - even a minuscule increase in effectiveness at large expense may seem worthwhile, if it increases the chances of survival of a loved one. However, one clear step forward is to require that a drug that is more effective and safer be preferentially used if it is not more expensive than an alternative. Though this simple condition seems like a no-brainer, it is not always applied - e.g. when a new, patent-protected drug is heavily promoted over a generic that is at least as safe and effective.
The last part of the book is titled, simply, Information - and it has perhaps the most lessons for other policy areas. Some of the chapter titles speak for themselves: "Signals, Noise, and the Big Void" and "Informational Kudzu" are my favorites.
...The idea, rarely articulated, is that there is no need for anyone to have oversight over what we know or what we prescribe, since with all those competing companies hawking their wares and touting the advantages of each, the practicing physician can just evaluate all the claims and counterclaims in order to decide which are the best drugs to use. The marketplace model has a logical corollary: no one has to worry about the impact of our prescribing on the public's health or the public till, either. Individual physicians, patients, and payers, each pursuing their own interests, will take care of all that as well. The whole notion, charming in its naivete, is similar in many ways to belief in Santa Claus or the Tooth Fairy..."
...The area of pharmaceutical company influence on physician decision making has become a small research field in its own right. The respected British Medical Journal devoted an entire edition to this topic; the issue's title, "No More Free Lunches," borrowed the name of an American website, www.nofreelunch.org, which tracks this problem. In an editorial the journal's editors declared that "doctors and drug companies [are] being entangled in an embrace of avarice and excess, an embrace that distorts medical information and patient care." Compared with the highly focused and effective influence of the manufacturers, the editors wrote, "medicine is a disorganised mess. Doctors have become dependent on the industry in a way that undermines their independence and ability to do their best by patients." Articles in the issue documented ways in which pharmaceutical sponsorship can distort the very design of clinical trials, as well as how they are reported and promoted to doctors. Physicians must also bear some of the blame for this situation, the editors argued, noting "it takes two to entangle."
As with policies in social science, environmental challenges, and so much else, improving information and policies for medicines would be difficult even if the only challenge was the tough science and stats required to understand which drugs are better and worse. The challenge is made much tougher by the skewed informational landscape, especially for patients and time-pressed front line doctors.
Avorn ends the book with a number of positive suggestions and solutions. Some are specific to his field, involving voluntary and regulatory measures. Others are broadly applicable, such as arming consumers with better information.
It's not enough for a solution to be theoretically accessible to a knowledgeable researcher - to make a difference, it must be readily accessible to the public at large, and be more credible than misinformation supplied by self-interested parties. In tandem with effective regulatory agencies and incentives, the easy path of making money through heavy marketing of inferior or inappropriate products can be made less attractive, and effort redirected toward the hard work and innovation necessary for true medical breakthroughs.
I found Powerful Medicines to be a real page-turner...a highly readable combination of science, human stories, systemic analysis, and policy discussion.
A related note, this side of the great pond we are starting to have some serious discussion on childrens medicine. One of the big problems in the current system is the absence of research in the field of childrens medicine (more specificly the application of ordinary adult medication on children). New medication is rarely tested for its effect on children (there's no money in this). As a result, dokters face the choice between no treatment at al or treatment with medicine as yet untested on children.
To combat this situation, the European Commission is putting forward a proposal to allow an extra year of patent protection for drugs whose effects on children have been adequately tested. As usual there is a lot amis with EC proposal, but it still looks to be a step in the right direction...
Great article ! Made me re-think about a situation closer home - my perfeclty normal three year old being put on diet by her doctor. My post on the topic after reading this