Our Unfounded Medical Optimism – Slate Magazine

Chris Gard and Connie Yates, the parents of terminally ill baby Charlie Gard, speak to the media on Monday in London.

Carl Court/Getty Images

The parents of Charlie Gard announced on Monday that theyd given up on treating their 11-month-old child, who suffers from a rare and deadly gene mutation affecting his mitochondrial DNA. The roller-coaster case began in February when physicians at the London hospital treating the infant said it was time to remove Charlies life support. They refused to let the British couple fly him to New York City for a last-ditch, experimental treatment that, according to its inventor, had a small but significant chance of reversing his brain damage. Over the past five months of legal battles, the hospital never wavered from its claims that every reasonable means of saving Charlie had been tried already and that he should be spared any further suffering that might come with a form of therapy that has never been tested on a patient with exactly his condition, and which isnt part of any clinical trial.

Daniel Engberis a columnist for Slate.

Charlies parents now say that its too late for any intervention and that its time to let him go. But for several months now, the #CharlieGard saga has served as the focus for a broader push for patients rights in Washington. Conservative politicians were quick to champion Charlies parents causePresident Trump tweeted his support and the House tried to grant the couple permanent residencyin keeping with the GOPs strong endorsement of so-called right-to-try laws. These measureslately passed in 33 statesare meant to guarantee very sick people access to experimental or nonconventional medical treatments that havent yet passed muster with the Food and Drug Administration. In practice, that means the parents of a dying patient such as Charlie wouldnt need to ask permission from the FDA to move ahead with therapy; they could just request it directly from the manufacturer.

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Its hard to argue with vocal patient-advocates who say their lives were saved by gaining access to experimental treatments. The right to try sounds like common sense: It should be up to patients to decide whether the potential upside of a treatment (surviving a terminal illness) seems worth any risk of painful side effects. Why not let them give it hell and go down swinging? But stepping back from anecdotes, the spread of experimental access laws (like the calls for Charlies puddle-jumping medevac) suggests that critical decisions about the final months of peoples lives are often based on biased judgments of reality. Patients seem to overvalue innovation, as a rule, and assume that newer drugs have a better chance of working than any other treatment, just because theyre new. Not only does this sanguine view of scientific progress fail to fit the facts; it also leads patients to the converse, false impression that nonconventional treatments arent likely to be harmful in themselves. A more sober view suggests that the hope that often moves people to seek out these types of treatmentsand the ever-present pressure to fight until the endis not as useful as we think.

The spread of experimental access laws suggests that critical decisions about the final months of peoples lives are often based on biased judgments of reality.

Unfounded optimism tends to be the rule in medicine. A 2015 review of several dozen studies of peoples expectations from treatment, comprising data from more than 27,000 subjects, found systematic evidence of a Pollyanna Patient problem: We overestimate the value of the care that we receive and underestimate its harm. That work is cited in an excellent article by Liz Szabo of Kaiser Health News, on the surprising ineffectiveness of cancer drugs that have been FDA approved. Its not just that these treatments do little to prolong survival, Szabo says; according to one study, many patients never grasp this fact. In a sample of several thousand adults, 39 percent said they believe the FDA only approves prescription drugs that are extremely effective; 1 in 6 asserted that drugs that have serious side effects cannot be advertised to consumers. Neither statement is even close to being true. According to Vinay Prasad, an oncologist and expert in evidence-based medicine at Oregon Health and Sciences University, we dont have any hard evidence of benefitin terms of patients living longer livesfor the majority of cancer drugs approved in recent years.

If FDA-approved drugs often fail to offer substantive benefits, then experimental onesthose that havent even passed the suspect bar for agency signoffare even less likely to be helpful. In fact, about 90 percent of experimental treatments flunk out during clinical trials, either because they arent shown to be any more effective than the standard treatment or because their side effects are too severe. In some cases, experimental treatments once thought to be miraculouslike the use of bone-marrow transplants as a cure for breast cancer, which started in the 1980shave turned out to be worse than ineffective in clinical trials. In the bone marrow case, the procedure could be deadly on its own. This abysmal failure rate persists in spite of the enormous cost of running trials and researchers clear incentive (read: bias) to produce positive results.

Such dire stats have done little to discourage eager patients, though. When it comes to clinical trials, we seem to harbor a version of the favoritelong shot biasthe tendency of horse-track gamblers to overvalue the underdog at the expense of the odds-on favorite. In medicine, this translates to fixation on the value of experimental treatmentsand the remote possibility that they might turn out to be wonder cures. Indeed, for those who are faced with imminent death, the desire to bet ones health on long-shot drugs (and the right to do so, when all other options have been tried) is so insistent that patients even deride clinical trials as another structure blocking access to potentially life-saving treatments. The trials randomized treatment groups and stringent inclusion criteria mean the majority of patients never get the chance to serve as guinea pigs at all.

In certain casesthink of early AIDS drugs or Ebola vaccinesthis rigidity can indeed have tragic consequences. But how much rigor should be sacrificed, and how many rules should be suspended, on behalf of patients whose expectations may be substantially inflated? In late June, that question served as the backdrop for a two-day symposium of doctors, bioethicists, patient-advocates, and public-health officials on the future of randomized controlled trials. The problems with RCTs are legion, speakers said: Theyre not well-suited to emerging threats; theyre too expensive; theyre too slow.

But it seemed just as clear from the proceedings that patients should think twice before they clamor for inclusion in these trials and for greater flexibility in their administration. The randomized trial is the single greatest medical innovation of the 20th century, said Prasad, who was in New York City for the meeting. But he warned against the use of massive studies of experimental treatments that may have only very tiny benefits in the end. Its unethical, he said, to put so many desperate patients on a drug unless you have good reason to believe in its effectiveness.

Even in this era of informed consent, patients may not understand exactly what they stand to gain (or lose) by entering a trial. Research going back to 1982 has found that many suffer from a therapeutic misconception: They assume theyll benefit personally from being in a clinical trial, though in fact they may not get the tested treatmentand even if they did, chances are it wouldnt help. (In fairness, some researchers now say this problem has been overstated.) My advice is, youre better off in the control group, warned former FDA chief Robert Califf in his keynote lecture at the symposium, speaking to prospective patients in the audience who had been arguing for greater access to experimental drugs. Most things dont work or theyre dangerous.

This creates an intoxicating atmosphere of progressa sense that new and better treatments are always on the verge of coming out.

The fact that an experimental drug is usually a bad bet isnt likely to dull our instinct to gamble on untested treatments, though. The idolatry of experimentation has even spawned a sinister, for-profit industry, lurking in the shadows of the FDA approval process. In a disturbing paper published last week, bioethicist Leigh Turner describes how the government website ClinicalTrials.gova registry established in 1997 to improve the reliability of formal research on potential treatmentsis being used to market sketchy medical practices. Patients who are looking for a way to break into a clinical trial may scan the registry for opportunities to volunteer; now, instead of finding only legitimate, government-sanctioned research trials, they could land on so-called patient-funded or patient-sponsored ones. In these, they have to pay for access to a therapy that isnt necessarily based on any peer-reviewed, preclinical data, and which may lack any evidence of safety or effectiveness. (Already there have been reports of patients suffering severe complications from their participation in these ersatz trials.)

What makes us so gung-ho for things that arent fully tested? It may in part be human nature, but aspects of the bias seem to be conditioned, too. Even honest science coverage tends to focus on putative medical breakthroughs that have either just occurred or may be coming soon; less scrupulous media figures hawk salves or potions with little basis whatsoever. Taken altogether this creates an intoxicating atmosphere of progressa sense that new and better treatments are always on the verge of coming out.

Top Comment

We're also too quick to pretend that a dead child isn't dead; Charlie Gard died months ago. Nothing that was offered would have changed that. I mention this because the other prob with have is an infantile faith in miracles. More...

Yet the excitement in the air rarely matches up to reality: Actual medical advancement tends to be incremental and excruciatingly slow. The discord this createsbetween the feeling of innovation inspired by the media and the real options that were offered in the clinicmay distort our view of experimental treatments. It could make us think there must be some reason why our cancers havent yet been cured; there must be some external factors preventing us from getting access to the new and better drugs weve heard so much about. If only regulators werent so overcautious and uptight, we end up thinking, it would be possible to tap this cache of innovation.

Right-to-try laws indulge the fear that unbending bureaucrats in Washington have kept patients from medical cures with an excess of red tape. In fact, these laws have little real effect. Thats because the FDA already offers access to experimental treatments with very modest oversightand in recent years the agency has done away with a few unnecessary rules that slowed the process down. The problem isnt that patients (or their parents) have insufficient freedom to decide how theyd like to balance out potential risks and benefits from experimental treatments. Its that our bias often makes them victims of false hope.