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Drug Shows Promise For Newborn Blindness


4 Star

Drug Shows Promise For Newborn Blindness

Our Review Summary

There was a lot to like in this story, and maybe that wet our whistle for how much better it could have been.  Room for improvement:

  • The story didn’t mention a key line from the study: it “was too small to assess safety.”
  • We understand, in general, why the story pits Avastin against Lucentis.  But in the context of this story, it isn’t explained adequately.
  • Some of the language was too vague.  For example, “An injection of Avastin stopped blood-vessel growth.” For all babies? The story later explains the problem came back in 4 of 70, but readers may not be able to connect the dots. (Read more below.)


Why This Matters

The study presents important evidence that could help many babies in the future and will likely lead to future studies. The article got the gist, yet there were some lapses in its presentations of the benefits, harms, and comparator treatments. We think these gaps combine to tilt the story into Avastin promotion, and addressing them would have centered the keel.


Does the story adequately discuss the costs of the intervention?


It gets credit for discussing the costs of Avastin.

In this review, we’ll keep coming back to the lack of context for the comparison to Lucentis. This article doesn’t discuss the use of Lucentis in this condition. Is it a real, off-label alternative or a hypothetical one? Since the study compared Avastin and a laser, the latter’s price tag would’ve been more relevant instead.

Does the story adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

Consider this rating a partial credit. We were happy to see some results in absolute terms and the important subgroup result for babies with type 1 disease. But the article gets enough dings to withhold a satisfactory grade.

First are the qualitative summaries. “An injection of Avastin stopped blood-vessel growth.” That’s a bit vague for such a zinger. For one thing, one of Avastin’s apparent advantages was that it doesn’t stop vessel growth in the peripheral retina. For another, does this sentence mean Avastin cured all babies? (Retinopathy came back in 4 of 70.) Or does it mean Avastin universally stopped vessel growth at the outset? (The main endpoint of the study was recurrence of disease. Maybe the laser also stops vessel growth at first.)

And we think the story could set a neater table before comparing the benefits of Avastin and the laser therapy. It names 3 downsides of laser therapy, but efficacy (50% recurrence in zone I disease) wasn’t one. Since the study was designed to compare recurrence rates, we assume this downside of the laser is prominent. Another downside of the laser was given: some babies need several treatments. But, in comparison, we’re told that “in many cases” Avastin only needed one treatment. “Some do” means the same thing as “many don’t,” so a cleaner comparison would’ve been nicer.

Here’s a final aside, not of the same magnitude as the prior comments. In an ideal world, the article could’ve addressed the different types of retinopathy of prematurity. Indeed Avastin was superior in the overall cohort, especially in Zone I disease, and the article accurately quotes the editorial as suggesting Avastin should become the treatment of choice in Zone I. But absent is the fact that this study showed no significant benefit in Zone II disease, the larger group of enrolled babies. There was a trend towards benefit, but it wasn’t statistically significant. The message from the editorial is that Avastin is possibly superior in Zone II, but we’ll need more studies. This thread would’ve added some nice balance to the story’s conclusion that Avastin “far surpassed” laser therapy in treating this disease, and would allow them to be more specific about the 15 hospitals that stopped using the laser (for whom? all zones?).

Does the story adequately explain/quantify the harms of the intervention?

Not Satisfactory

Room for improvement. We give the article credit for noting that Avastin has limited safety information in this setting and that the investigator has noted no significant side effects in this cohort. It also gives some theoretical reasons to be optimistic. But what’s missing from the story is the key line from the study: it “was too small to assess safety.” You know the saying about absence of evidence and evidence of absence?

As noted, as readers we are unclear why Avastin is sparring with Lucentis. The article elevates Avastin because it “can’t easily travel outside the eye,” while Lucentis has a theoretical concern of systemic effects. That paragraph gave us several itches:

  • The editorial tallies Avastin’s potential for systemic side effects as one of its disadvantages.
  • Without knowing the role of Lucentis in therapy, it doesn’t matter much how it stacks up to Avastin hypothetically. Without more context, it seems like a straw comparison that serves to make Avastin look safe.
  • The study states that a much larger trial would be needed to investigate Avastin’s potential for systemic side effects. That means the jury is still out, and systemic side effects are a live concern.

The article states that the 7 deaths in the study were unrelated to either treatment. We don’t see that conclusion in the publication or editorial. Perhaps it was based on an interview with the lead researcher? If so we’re unable to verify, since we can’t interpret the raw mortality information on the 7 cases in the study report ourselves. With that caveat in mind, we note that, to us, the study report seems to suggest that their study was too small to determine whether Avastin is associated with more deaths than is laser therapy. Since there were more deaths in the Avastin group (5 vs 2), we would’ve liked more clarity around this topic.

Does the story seem to grasp the quality of the evidence?


The story provides lots of good details on the study design, including the publication status, size, randomization, multicenter nature, comparator, number lost to follow-up, and a qualitative description of the follow-up period.

See the “Harms” criterion for a critically important limitation of the study size. A bit more specificity on follow-up wouldn’t have hurt.

A quibble: The article says that the study enrolled “About 150” babies, but then it discussed them in groups of 143 and 7. Isn’t that exactly 150?

Does the story commit disease-mongering?


There’s no real mongering here.

As a side note, the article cites statistics regarding the disease in general. Since the study only enrolled a subset of babies with this disease, it would be interesting to know how representative its sample was.

Does the story use independent sources and identify conflicts of interest?


The independent source was the NEJM editorial. We prefer to see more outside analysis of a study, but the editorial is an important source.

General conflicts of interest are identified. (Although the sources made some additional disclosures to the NEJM, none were overwhelming.)

Does the story compare the new approach with existing alternatives?


The study itself compared Avastin to standard therapy, and the story reports enough of the comparison to earn a score. However, we see a few ways the comparisons in this story could’ve been sharper. (See our comments under the “Benefits” criterion for a related critique.)

We’ve logged confusion about pitting Avastin to Lucentis. There may be a good reason, but we don’t think WSJ readers get it. The only use of Lucentis discussed is in grown-up eyes. Is it compared to Avastin just because they’re “similar” drugs and because Lucentis has at least some eye indication? Or is Lucentis actually used off-label, or such use has been proposed, in this disease? Without that missing piece of the narrative, it’s kind of difficult to weigh the meaning of Avastin’s cost and pharmacologic advantages over Lucentis.

It may be hard to find perfectly balanced patient testimonials for a story like this, but it’s worth pointing out that the Henry family’s experiences may not be the most level illustration of this study’s results. Evelyn had a great outcome from Avastin. Her sister Grace had the laser and a very regrettable outcome, losing an eye from glaucoma. For one thing, it’s only implied that the culprit was the treatment, not her disease, which, we’re told is associated with retinal detachment as opposed to glaucoma — but the article could’ve been clearer about causality here. More importantly, the relative side effects of these two procedures were never discussed in the scientific portion of the article, and we don’t see any discussion of the potential for very serious side effects from the laser. If it is such a distinguishing factor as to color the entire testimonial section, we would’ve liked to hear about it in the discussion of pros, cons, and research.

Does the story establish the availability of the treatment/test/product/procedure?


It’s clear that we’re talking about an off-label use of an available drug.

Does the story establish the true novelty of the approach?


The novelty in the approach is well described. We’re told how the drug works and some differences with the laser therapy, for instance, related to the type of anesthesia.

Does the story appear to rely solely or largely on a news release?


We didn’t find signs that the article relied on a news release.

Total Score: 8 of 10 Satisfactory


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