Hopes and realities:

Research into the placebo effect in autism can be broken down into three rough categories. The first of these is the result of an experimental necessity: Most measurements in a clinical trial rely on parents’ observations. “Parents are exquisitely attuned to very subtle variations in behavior that may not really be apparent to other observers,” says Adrian Sandler, medical director of the Olson Huff Center at Mission Children’s Hospital in Asheville, North Carolina. Sandler worked on the first placebo-controlled secretin trials.

In autism studies, the participants themselves generally do not report how they feel; instead, parents or researchers report their observations of the participants. As in Merryday Porch’s case, many parents notice changes after a treatment that don’t exist. This phenomenon is by no means limited to parents of children with autism. A group of scientists from the Menninger Clinic in Houston, Texas, gave sweet drinks to children whose parents described them as sugar-sensitive. Unbeknownst to the parents, the drinks were actually sugar-free, but parents still rated their children’s behavior afterward as more hyperactive and erratic than before.

Along these lines, facilitated communication — a popular technique in which children with autism use a keyboard as an assistant guides their hands — has turned out to be a modern-day Ouija board, driven by the wishful thinking of the assistants. The placebo effect doesn’t only interfere with observations made by parents and caregivers: Physicians can also easily become persuaded to see improvement in a child.

One wrinkle here is that often the observed progress isn’t a mirage. In any course of treatment, people tend to take medicines when their condition is at its worst, and then attribute the relief they observe to the medicine rather than to the condition’s natural course. Besides, development in all children happens in fits and starts. A well-timed vitamin supplement can seem to be effective when, in reality, the change is due to a natural spurt in development.

The second way placebos play out in autism research is more complicated. Even if a parent is able to suppress the desire to see a positive outcome, she may reveal signs of her excitement. A new therapy can breathe hope and anticipation into a household. Children, being naturally observant of their parents, may respond to this atmosphere by masking symptoms in order to please their parents. This kind of ‘placebo-by-proxy,’ in which children pick up on cues and expectations from their parents, is common throughout pediatric research because, among other reasons, children are highly suggestible.

“Are we seeing things that are simply just relating to a parental placebo effect? Or are parental expectations influencing the child, and then the child’s behavior changes?” asks Rebecca Jones, a neuroscientist at Weill Cornell Medicine in New York. To pin down parents’ role in the placebo effect, Jones, along with Weill Cornell clinical psychologist Catherine Lord, compared the accuracy of observations made by parents and clinicians with objective, quantitative measures. The results are unpublished, but Jones says they suggest that researchers must take into account the contribution of expectation from all of the parties involved — the trial participants, parents and clinicians.

In fact, parents’ opinions seem to predict how a child responds to placebo. For example, multiple studies have found that children whose parents are optimistic about a trial’s results at the outset have a more robust placebo response than do children of more clear-eyed parents. A 2012 study showed that children prone to tantrums have fewer spells after they drink a flower essence that supposedly calms children, but is actually a placebo. The concoction seemed to work, but the researchers found that its success was more closely tied to the expectations of the parents than the observed behavior of the children.

“If the adults expect little, they get little; if they expect a lot, they get a lot,” says Ami Klin, director of the Marcus Autism Center in Atlanta and a professor at Emory University.

This disconnect between observed reality and biological reality makes it extremely difficult to measure how a treatment is performing in a clinical trial. In other words, expectation constantly muddies the scientific waters. Sometimes, a placebo apparently affects researchers more than it affects the participants: In a 2009 meta-analysis of trials for depression treatments, researchers rated the participants’ improvement almost three times higher than the participants themselves did. In a similar meta-analysis of irritable bowel syndrome treatments (a favorite topic of study for placebo researchers because of its high placebo rate), the clinicians rated improvement 50 percent higher than the participants did.

It’s difficult enough to separate placebo from drug effects when participants report their own experiences, says Karin Jensen, a placebo researcher at the Karolinska Institute in Stockholm, Sweden, but it’s nearly impossible when other people are in the mix. The excitement in the media and the autism community over the secretin trials is a perfect example of this phenomenon, she says. “Most of [autism research] is based on subjective ratings,” she says. “Expectations were sky high, and so that was transferred to patients via parents and caretakers.”

Of course, not all placebo responses are positive, especially when it comes to the wide world of questionable therapies. If a treatment is painful or uncomfortable, and a child is afraid of the therapy, she might change her behavior to mask her condition. Although there’s little research into how fear might change the behavior of a child with autism, some in the autism community are convinced that it can play a big role.

Emma Dalmayne, an autism advocate, has the condition, as do five of her six children. She says uncomfortable sham treatments — such as bleaching agents that can damage the digestive system — can cause a child to pretend to feel better out of fear. The treatments may seem to the child to be a punishment for her autism-related behavior. “Children aren’t stupid,” Dalmayne says. “If you’re a child and you’ve been told you’ve got monsters living in your tummy and your mom wants to flush you with bleach,” she says, “you are going to stop the stimming behavior, the vocalizing and the flapping.”

Misled by this sort of placebo effect, families may waste precious time, energy and money on worthless treatments that, over time, may even be dangerous.