The trial is legitimate. It’s partially funded by the California Institute for Regenerative Medicine, the state's stem cell agency; well-known spinal experts are participating; and the FDA has certified the treatment as one that preliminary clinical evidence indicates has the “potential to address unmet medical needs” related to a “serious or life-threatening disease or condition.”

There have also been a steady stream of media reports about the possibility of a breakthrough, including our own coverage and a recent feature by Discover magazine and front-page story from the San Francisco Chronicle.

"'Super exciting' results in stem cell therapy trial," was the headline, quoting Dr. Edward Wirth, the chief medical officer at Asterias.

It's Still Early

Regaining two motor levels in spinocervical patients is significant. That level of improvement could mean the difference between full paralysis from the neck down, requiring a ventilator to breathe, versus regaining some arm, hand and finger movement, enabling patients to take care of many of life’s daily tasks unassisted.

Below is video of Kris Boesen, a patient in the trial who at the age of 20 was paralyzed from the neck down.

"I couldn't drink, I couldn't feed myself, I couldn't text or pretty much do anything," he says. "I was basically just existing."

But after the stem cell treatment, he says, "I'm able to live my life."

Another trial patient, Lucas Lindner, was in a car accident that left him a quadriplegic, with no use of his hands or legs. After receiving the stem cells, he recovered to the point of being able to throw a ball, type and use a soldering gun.

These are compelling stories. And if the treatment really does work, it could provide hope to traumatic-injury patients who might otherwise show little progress or improvement in their paralysis.

But of course, the sample size we've seen so far is small — really small — just six patients. And it's true that some patients have been known to spontaneously recover some movement after spinal injuries without having received a cutting-edge stem cell treatment. Also, in this second phase of the trial, there is no control group. A double-blind, control-group study is planned in Phase III next year.

So we wondered, how can the people running the trial know, right now, that the level of improvement in their subjects is favorable to patients who haven't received the treatment, prompting such optimistic press releases? And how much excitement should anyone allow themselves over these early results?

Using Historical Data to Compare

The likelihood of all six patients recovering to the degree they have on their own is unlikely, researchers say.

“This is as good as you could hope at this point,” said USC's Liu, in March. “So far all the evidence is pointing in the right direction."

Asterias, based in Fremont, Calif., has tried to assess these early results by comparing the improvement in its cohort of patients to historical data from an estimated pool of 3,300 spinal injury victims in the European Multicenter Study about Spinal Cord Injury. Asterias says the level of progress for its six subjects is about twice the rate of recovery patients saw in the European data, dating back to 2001.

"The 12-month data showed 67% (4/6) of Cohort 2 (subjects) have recovered 2 or more motor levels on at least one side through 12 months, which is more than double the rates of recovery seen in both matched historical controls and published data in a similar population," the company wrote in an October press release.

But according to Oswald Steward, director of the Reeve-Irvine spinal cord research center at the UC Irvine School of Medicine, there are so many variables to be considered when you look at historical data, you really have to take any conclusions with a few grains of salt.

“It sounds good, but it’s not a control group, there’s no real data here," Steward says. "It’s nice to give some background, to give you a sense of [comparative recovery rates], but that’s definitely the way I would put it."

Getting background information to give a rough framework of comparison is exactly what the company wanted to accomplish, according to Wirth, Asterias' chief medical officer.

"The take-home message is that we can only hope to truly demonstrate efficacy in a randomized control trial," he says.

That's the plan in Phase III of the trial. "The historical controls are merely a temporary comparator to help us determine whether the ... program should move forward."

An Unusual Step

Historical data is often used in cancer studies because of the fixed nature of outcomes in some cancer types, but it's unusual to see early-stage clinical trials in other areas use it as a comparison, says Karen Messer, chief of the Biostatistics and Bioinformatics division at the Moores Cancer Center at UC San Diego Health.

“Use of historical controls is common in early-phase cancer studies because they usually have small sample sizes and the end points are really well-defined," she says.

But spinal cord injury outcomes may be more varied, Messer says, so the results of an intervention wouldn't be as reliable.

“(T)here are a few things to watch for: Are the patients comparable? Has treatment changed? You want to make sure the response assessment is not subject to any judgment calls.”

Asterias mined the European historical data because it was the only large spinal-injury database with current information that could be licensed, Wirth said in an internal memo on the rationale and methods for compiling historical data.

In that memo, Wirth wrote that some variables are not included in the European database. These include MRI data on spinal cord lesions and the timing or quality of decompression, a bone-trimming surgery that makes more room for nerves. These differences in the data make direct comparisons harder.

Diana Miglioretti is a biostatistics professor at UC Davis. She says historical data is an interesting approach to frame a comparison.

“Obviously it isn’t as strong as a control group,” she says, “but if there aren’t major time trends, it can be a reasonable alternative.”

In other words, Miglioretti says, if outcomes haven't changed over time — due to improvements in treatment, for example — it's not out of the question that historical data can serve as a control.

But according to spinal cord researcher Steward, that’s the main concern about taking historical data on spinal injuries at face value .

“In the past we treated spinal injury differently,” Steward says. “For instance the amount of time people spend in rehab is a lot less than it was 10 years ago.”

Strong Anecdotal Statements

From Steward’s point of view, the real reason to get excited about the phenomenal initial results of this stem cell therapy is not the supporting historical data, but rather the anecdotal statements by the clinical researchers.

For instance, he points to the statements by Richard Fessler, the lead investigator of the Asterias trial and a professor of neurosurgery at Rush University Medical Center in Chicago. “I’ve been treating these kinds of patients for 30 years,” Fessler said in the San Francisco Chronicle story, “and I’ve never seen anything like this before.” (Fessler has no financial stake in Asterias, company officials say.)

“When someone like Fessler says 'I’ve never seen anything like that,' ” Steward says, “I spend more time listening to that than to historical data.”

Steward also points out that this stem cell therapy won’t help those with chronic spinal injuries, but says it could be a game-changer for newly injured patients.

“Still, this is huge,” he says. “Things are progressing in a positive way. No bad outcomes, and people seem to be improving in a way that may be unprecedented. As a scientist I think it’s very exciting.”

spinal injuriesspinal injuries

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