Amid today’s interparty rancor, health care experts looked back on Monday at more tranquil times — say, December 2016 — when Democrats and Republicans worked together to pass legislation to fight cancer and other diseases, to boost research funding, and to speed potentially life-saving innovations to market.
Panelists at the Harvard T.H. Chan School of Public Health wondered whether the legislation, signed by President Barack Obama on Dec. 13, will live up to its promise. The 21st Century Cures Act authorizes $6.3 billion over 10 years in additional research spending, much of it for the National Institutes of Health (NIH), which is a major funding source for academic studies around the country.
The act authorized such spending, yet panelists pointed out that doesn’t mean the money definitely will be in the budget, because it still must survive the scrutiny of both the new administration and Congress.
Some panelists also cautioned that the act’s promise to speed new drug approval by the Food and Drug Administration (FDA) — intended to get new treatments to patients quicker — may yet have a downside. Running clinical trials takes time. By speeding the process, compounds may get onto the market that are not as thoroughly tested as in the past. Otis Brawley, chief medical officer for the American Cancer Society, said mere ineffectiveness is not the worst thing that can happen with a new drug. In the past, people have been harmed by flawed compounds and medical devices meant to help.
“I hope we don’t do that in the future, but I fear we will,” Brawley said.
Brawley described the act as a compromise, and he and other panelists hailed its promised increase in research funding. The funding is allocated mainly to brain research, precision medicine, and regenerative medicine. It also will support the “Beau Biden Cancer Moonshot,” named after former Vice President Joe Biden’s son, who died of brain cancer in 2015.
Aaron Kesselheim, associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital and director of the Program on Regulation, Therapeutics and the Law, pointed out that NIH funding has held roughly flat for more than a decade, resulting in a decline, when inflation is considered, of 22 percent.
Jeffrey Drazen, editor in chief of the New England Journal of Medicine, said it would be “wonderful” if the promised funding is actually approved, but he warned of a continuing concern that funding would fluctuate year to year, which would disrupt research begun when funding is up, forcing abandonment of potentially promising new ideas.
“The NIH is undergoing a slow strangulation,” Drazen said. “Money is what drives research. You need the resources when you have an idea.”
Drazen and the other panelists spoke at The Forum at Harvard T.H. Chan School of Public Health. The event, “The 21st Century Cures Act: Implications for Research and Drug Development,” was co-sponsored by the medical news web site STAT.
Both Kesselheim and Brawley raised some concern about speeding up the FDA’s drug approval process, saying that will result in decisions based on less-rigorous science. Brawley said that means more drugs will be approved whose negative or harmful effects won’t be detected until they’re in broader use. That is why, he said, the FDA should boost post-approval monitoring so that drugs that prove harmful once on the market can be quickly detected and recalled.
“Many parts of the bill overemphasize speed over science,” Kesselheim said.
However, Pamela Tenaerts, executive director of the Clinical Trials Transformation Initiative, disputed whether a faster approval process means a less rigorous one. The shift does allow the agency to consider additional evidence, such as patient experience, which she said would provide potentially valuable perspective about how a drug performs in the real world. She agreed, however, that smaller trials are not as revealing as large clinical trials, and that it’s important that patients enrolled be apprised of risks involved.
“Smaller numbers come with greater unknowns,” Tenaerts said.
The changed medical and health care landscape may also make it tougher to run large clinical trials, Brawley said. In the 1980s, when he did a lung cancer trial, there were believed to be two major types of lung cancer, and researchers were able to run trials with 200 subjects each. Genetic testing has since revealed that there are about 80 types of lung cancer and it’s harder to find people with each subtype, meaning that trials on specific types are much smaller, and so their conclusions have less scientific rigor.
Much of the law’s success, Brawley and Drazen said, will hinge on the abilities of FDA officials to wield the additional flexibility that the statute allows them to grant wisely.
“I look at the current FDA and see some wise people there with a good track record,” Brawley said. “I think they’ve walked a very fine tightrope.”
Pharmacovigilance is the collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products. Pharmacovigilance heavily focuses on adverse drug reactions, which are defined as any response to a drug which is noxious and unintended, including lack of efficacy. Medication errors such as overdose and misuse and abuse of a drug are also of interest.
More than 250 million prescriptions for painkillers are written each year in the United States. Enough were prescribed in 2010 to medicate each American adult every four hours for a month. Americans, about 5 percent of the world’s population, account for 99 percent of the world’s hydrocodone (Vicodin) consumption, 80 percent of the world’s oxycodone (Percocet and OxyContin) consumption and 65 percent of the world’s hydromorphone (Dilaudid) consumption. All the while the use of illicit drugs, including non-prescribed painkillers, continues to grow.
It’s no longer a secret that the substantial swath of Americans living under the influence of these opiates do so with at least the tacit approval of our political system. Our law enforcement agencies, after all, focus on only a small number of the poorest users (and then only the few who become addicted and engage in crime), and our taxpayer-funded healthcare programs support the epidemic by spending billions annually on these drugs. Moreover, government-sanctioned discussions of the problem typically revolve around addiction-related crime; the devastation the drug has brought to many small, rural communities; the spread of opioid use into the white middle class; or the easy transition to heroin use. Recent negotiations in Congress, touted for their bipartisan nature, are designed to make treatment and the anti-overdose drug Naloxone more available to addicts. There are also proposals to fund school-based educational programs and to limit the practice of “doctor shopping.” Analyses of the root causes of the epidemic as well as the inordinate profits of the pharmaceutical industry are typically left to reporters and filmmakers. But very little attention has addressed a most basic problem: Why are our elected officials not confronting this widespread drug dependence with the goal of limiting it, rather than trying to make addiction treatment more available?
Consider this analogy: Constipation caused by regular opioid use is now so common that there are medications marketed for opioid-induced constipation (OIC). That drug’s consumers are numerous enough to warrant an expensive Super Bowl commercial, one that depicts long-term opioid use as a given, and its amusingly chronic side effect as an easily treatable annoyance. According to the pharmaceutical industry, it’s the unfortunate consequence of long-term use that must be addressed. A second industry commercial mentions several specific side effects of OIC medications: a tear in the stomach or intestine and opioid withdrawal, for example. Another set of drugs designed to treat these symptoms is probably in the works, creating an expanding cycle of pills made to lessen the side effects of other pills, and so on. Though profitable for drug-makers, the pattern avoids the real problem while treating one set of symptoms after another.
This “symptom-response exchange” that occurs in the pharmaceutical industry intertwines with a similar symptom-response exchange taking place in the social world, where systemic problems are ignored while symptoms are addressed: A lack of jobs is responded to with medications; resulting crime elicits prison, which weakens families; broken families are responded to with welfare benefits, which breed dependence; and so on.
Perhaps the public furor elicited by the Buffalo case provides a hint of what would occur on a much wider and more active scale if fewer Americans were chemically numbed, or if their ready access to drugs were threatened, and if they instead confronted what they experience as painful lives. In tentative and understated ways, these otherwise silent Buffalonians pushed back on a system they had found nonresponsive. Previously mute, they found a voice. They demanded to be heard, and this time they were. In the end, they were not denied access to the painkillers that allowed them to get on with life and to be happy, even if for some it meant doing so in “zombie-like” fashion.
The personal assessments of hopelessness by the chronically poor and the former working class reflect what is often an objectively harsh reality, one that includes inferior education, lost jobs, low and stagnant wages, and little prospect of upward mobility. In a sense, the world they grew up in and anticipated living in has vanished. For the hollowed-out middle class, it’s frequently a life filled with the apprehension that accompanies continual change, and the fear of falling into the void that waits below. In this context, readily available and subsidized pain relievers offer an alluring promise of a more tolerable existence. It’s a promise that’s kept more reliably than are similar pledges offered every election cycle by mainstream politicians who are no longer believed.
Certainly, the benefits of widespread opioid use are understood by our elected leaders, especially in an era when respected pundits, viewing angry mobs, speak of a possible need to “restrain democracy.” It’s quite possible that during an era of gross inequality and low-paying, no-benefits jobs, a numbed electorate may be viewed favorably as an apathetic citizenry inclined to accept the status quo, even one that is traumatic, frightening, cruel, unfair, or lonely. It’s a status quo in which former sources of meaning are crippled or dead. Data on marriage and divorce rates, as well as those on non-marital childbearing and marital satisfaction levels, show that for the poor and working class, the family has effectively collapsed; jobs that provide a sense of dignity, control, and the wherewithal to provide for oneself and others, are gone; and religion’s capacity to nurture the spirit has broken down and a vibrant group life of neighborhoods has failed to replace it.
This reality has been ignored by those who helped create it. Only now, as darkness falls on a troubling presidential campaign, is the political class, suddenly worried about its own job security, conceding the devastation their policies have inflicted on so many. Unbalanced, international trade agreements and rampant outsourcing, the voiceless are finally told, might have been mistakes.
But what if they weren’t mistakes? What if these decisions were made with the knowledge that they would benefit the few and hurt the many? What if we have constructed a society in which there cannot be meaningful jobs for all who want them; a nation incapable of making all of its citizens literate; a place in which the sources of stability in families and neighborhoods cannot be resuscitated; one in which houses of worship and voluntary associations can no longer sustain a shared set of altruistic beliefs? What if, unwilling to provide the conditions necessary for contentment, our leaders are settling for a state of indifferent acceptance, one in which, rather than a reasonable income or usable skill set, they offer the disaffected a prescription?
Karl Marx wrote, “Religion is the sigh of the oppressed creature, the heart of a heartless world, and the soul of soulless conditions. It is the opium of the people.” By encouraging compliance and promising relief and contentment after death, religion convinces the exploited and the alienated to endure a burdensome existence. But Marx also believed that religion was a form of protest against those oppressive conditions, one that could become as real as the suffering itself. In this context, opiates may be fulfilling the political function once met by religion by keeping the masses quiet; but it could also be where the “revolution” begins: with the refusal of a small group in Buffalo to allow their comfortably numb lives to be threatened. When that distorted reality is interfered with, as one day it will likely be, the collapse of institutionalized widespread chemical pain relief could prove Marx right, sort of.
Religion’s grip on the lower classes has loosened considerably and may soon lack the ability to placate an expansive and increasingly diverse category of people. Soon, the truth in the metaphor underlying Marx’s observation may be reversed, with opiates becoming the religion of the masses, tied to shared beliefs, common rituals, and sacred objects. It may be the opioid epidemic that is the sigh of the oppressed creature, a lament for what has been lost, a distorted vision of a contented life worth rebelling for, a cry for change.
Marx believed that the premise of all criticism is the criticism of religion, that a critique of religion would lead to the critical assessment of other social institutions. In the United States today, an analysis of the opioid epidemic leads to an understanding of the profit-driven pharmaceutical industry, which in turn triggers a critique of the economy, and then of the political system that facilitates it, and so on.
Many of the Buffalo doctor’s supporters, for example, denounced those politicians who threatened easy access to painkillers, saying they were only trying to make a name for themselves and get votes. Others condemned the profit-hungry pharmaceutical industry for creating such widespread dependence in the first place. One comment cut to the core of the issue by asking what one was to do when life was defined by psychological or physical suffering: “If there is no cure for what a person has, should that person just curl up and suffer? Go from doctor to doctor trying to find some kind of mental relief—even a psychiatrist and therapist for months and years? Go from doctor to doctor for months and years looking for and praying for physical relief? Or just call it quits and find someway to end their life?”
In our secularized world, suffering and praying have lost their cachet; suicide has not, with rates increasing alarmingly among the white working class. For now, those who protest their diminished lives have limited themselves to rowdy displays of support for a man who promises to resurrect what has been lost. In Buffalo, confronted with the unwelcome prospect of viewing reality soberly, a group of people formed a small and angry congregation outside a closed pain management clinic.
SYMBIOSES INSIDE HUMANS
The richest riskiest symbioses are playing out inside. The human body is home to 100 trillion microbes in mobile constellation. A mere 100 million stars, by comparison, make up the Milky Way. On our skin, encircling our orifices, throughout our guts and even within our cells, their genes outnumber ours by 500 to one. The changing census of these microbial presences, both tourists and residents, is our individualized microbiome. It is shaped by the food we eat, the company we keep, whether we were born vaginally or cut out of our mothers, fed from the breast or the bottle. A rough-and-ready measure of a healthy symbiosis is if our bacterial communities are not seen, smelt or felt. We ignore their mainly reliable, diligent and beneficial labor: they are our silent majority.
The presence of a defensive microbe can force a pathogen to become less virulent. Defensive microbes can also steal vital proteins from pathogens to make themselves stronger, causing the pathogens to evolve to produce fewer such proteins. This, in turn, makes the defensive microbes weaker – but enough damage has already been done to the pathogen to stifle its future growth and virulence.
Humans can start to risk considering microbes as allies. In Occident, infectious disease is no longer the leading cause of death. But to divide bacteria into two flavors, the baddies that make us sick and the goodies found in yogurt drinks, is to oversimplify an intriguing mess. Microbes don’t have static identities, and they don’t behave the same in different parts of our bodies. What’s untroubling in the gut can burn through the urinary tract or, if we’re unlucky, run riot in the blood. This is sepsis, and this can kill you.
HIDDEN BENEFITS OF TV DRUG ADS
We have all seen the ads: an earnest employee or parent who complains of fatigue but with the help of a specific drug is able to get back on the job or play catch with the kids in the backyard. These TV pharmaceutical advertisements, known as direct-to-consumer (DTC) ads, are ubiquitous—with drug makers spending $3 billion dollars a year on them in 2012. Yet they remain controversial among economists and other industry observers.
There’s a longstanding economics question about the effects of ads. Do they provide helpful information or just try to persuade people to buy a particular product.
Some argue that drugmakers use DTC ads mainly to steal business from rivals. This results in a costly arms race that guides consumers toward one of several negligibly differing, expensive branded drugs over equally effective generics. At the extreme, that line of argument supports banning DTC ads.
But other economists suggest DTC ads offer patients important information, boosting overall demand for classes of drugs that can genuinely help people, and ultimately serve a preventative role that benefits society as a whole. After all, some types of drugs, such as cholesterol-lowering statins, provide a broader societal benefit by preventing costly and life-threatening heart attacks.
To get at the true effects of these pharmaceutical ads, Starc took advantage of their displacement during the months preceding the 2008 presidential election, when campaign ads dominated people’s screens instead. Specifically, Starc examined how the absence of DTC ads impacted drug sales of four cholesterol-reducing statins.
The U.S. is unique in allowing DTC ads. New Zealand is the only other country that does. There are a lot of policy implications of this kind of advertising, so we were excited to do the research.
While the ads did cause some people to switch to a different brand-name drug, the overall benefit to society of encouraging consumers to try the drugs outweighs these costs. Given the health and financial benefit of taking a pill versus having a heart attack, she calculates that the benefit of the statin ads is enough to justify all spending on DTC ads.
We know statins reduce the number of heart attacks people have, and large numbers of people on statins are on government-funded Medicare, so if they have a heart attack, that’s very expensive for Medicare to cover. As taxpayers, we’d rather pay the $3 a day for a statin than the high cost of hospitalization for a heart attack.
If you think these ads increase demand for a cost-effective drug, then that’s a practice you don’t want to ban but to encourage. DTC ads for statins boost sales for more than just the single drug being advertised. Ads have positive effects when you consider the category as a whole. When you see a Crestor ad, you’re more likely to get Crestor, but you’re also more likely to potentially get one of the older drugs that’s off-patent, which we can see as positive spillover.
This informational effect of DTC ads, in the case of statins, promotes healthier choices by a larger group of consumers. That the advertising is getting more people to take statins is good from a social standpoint. In fact, the ads do significantly draw prescriptions away from competitors. The findings showed that revenue for branded advertised drugs would have been up to 24% higher in the absence of rival advertising. The “you advertise, so I have to advertise” mentality within the industry may result in more advertising than is truly needed.
Still, because of the overall benefits that statins provide, the value to society of direct-to-consumer advertising is positive on the whole. Meaning, even if companies are prompted to use DTC ads because of competition, the overall impact is good. In fact, banning DTC ads would lower sales of unadvertised drugs by about 4%.