This story attempts to explain why the FDA seems hesitant to approve a drug named Avodart for the prevention of prostate cancer. (It also diverges briefly into the discussion of a second drug, Proscar, which isn’t the main focus of the story and won’t be addressed in our review.) The key point — which the story communicates well — is that the drug prevents low-risk cancers but seems to encourage the growth of aggressive ones. So the the data require close scrutiny to see whether there’s an actual net benefit to patients who are treated with the medication. Unfortunately, the story fell short in its coverage of some of the other areas that we feel readers deserve to see addressed. Detail about costs and harms is especially important in a case like this where a drug’s purported benefits appear to be marginal–and yet the story provided no information.
Prostate cancer is second only to lung cancer as a cause of cancer death among men in the United States. However, it is important to keep in mind that the disease is diagnosed in many more men than it kills. This is because most prostate cancer is so slow-growing that patients typically die of something else before the tumor has a chance to spread. The most pressing need, therefore, is for techniques that can identify and eliminate the aggressive tumors, which are causing the lion’s share of the death and damage. We certainly must look cautiously on any therapy that may increase the risk of these high-risk cancers, even if it prevents the low-risk ones.
A problem with research in this area is that the ultimate goal of therapy ideally should be to prevent death from cancer. However, the number of patients, years of follow-up, and costs needed to show a survival benefit are prohibitive. Consequently, studies target the more easily measured surrogate endpoint of cancer incidence–which may be a meaningless endpoint for the reasons described above.
No costs are mentioned — not acceptable when the drug is already on the market and cost information is easily obtained. According to one estimate our reviewer found within minutes, treatment with Avodart costs about $4 per day. Previous analyses of finasteride, which has a similar mechanism of action, estimated that the cost per quality-adjusted life year (QALY) gained from treatment far exceeds $100,000/QALY. An acceptable cost effectiveness for a treatment is considered to be less than $50,000/QALY.
A couple of problems here. First, the story describes the overall cancer prevention benefit for Avodart in relative terms (“a 23% reduction”) but never gives us the absolute numbers. It would have been much more meaningful if the story had told us, as the original study did, that “659 of the 3305 men in the dutasteride [Avodart] group (19.9%) and 858 of the 3424 men in the placebo group (25.1%) received a diagnosis of prostate cancer, representing an absolute risk reduction with dutasteride of 5.1 percentage points.” (As noted above, even these absolute risk data are somewhat misleading.)
Second, a Glaxo representative makes the reasonable point that although the cancers prevented by Avodart may be slow-growing, many men with these kinds of cancers undergo invasive surgery that reduces their quality of life. To understand the scope of this benefit, however, it is important to know just how many men with these lower-risk cancers go on to receive surgical treatment, and what kinds of consequences they might avoid by taking the drug. Otherwise there’s no way to measure this benefit against the potential harms of treatment, such as increased risk of aggressive cancer and sexual dysfunction.
Use of Avodart is associated with increased risk of sexual side effects and a small increase in heart failure risk. The story didn’t mention these potential problems.
The story gives a decent overview of what happened in the REDUCE study, which is the trial that Glaxo is using to support its application for Avodart. It’s clear that this this was a large placebo-controlled study designed to generate enough high-quality evidence to satisfy FDA standards. And it was important to point out that Avodart, despite lowering the overall risk of prostate cancer, may have increased the risk of aggressive cancers that are more likely to be lethal. The prevention benefit was for lower-risk tumors that would never have caused a problem for most men. So the overall risk-benefit calculation for this drug is more complex than it might appear at first glance.
Nevertheless, the story missed some elements that are critical to understanding the results. Notably, it didn’t explain that the study investigators biopsied men after the 2nd and 4th years of treatment, regardless of whether their was a clinical reason (such as elevated PSA levels or an abnormal digital rectal examination) for doing so. Therefore, the cancer detection rate was substantially inflated–the 19.9% rate in the Avodart group, while lower than the placebo group, still exceeds the expected lifetime rate of about 16%. When the authors looked at cancers detected for clinical reasons–the real world experience–there was no difference in cancer detection rates.
A close one, but we feel the story did not provide enough context for readers to judge the real world importance of the findings. The story might have done a better job here had it included more independent sources in its coverage.
The story only delivers information from an FDA documented posted online and from a drug company spokesperson. So, in fact, we don’t hear from a truly independent voice and not from any expert in clinical care either.
There are no proven ways to prevent prostate cancer (although supplements such as vitamin E and selenium have been found to be ineffective), so we can’t fault this article for not mentioning any. We’ll call it not applicable.
The story makes it clear that Avodart is approved by the FDA for treatment of non-cancerous enlargement of the prostate. It also explains that Glaxo Smithkline is seeking new approval to market Avodart for the prevention of prostate cancer. The story could have been more clear about the fact that Avodart can already be prescribed off-label for cancer prevention (even though it is not officially approved for this), and that the FDA approval would sanction this existing use as well as expand it to other clinicians and patients.
The story doesn’t try to oversell the novelty of using Avodart to prevent prostate cancer. But it could have made it clearer that the effects seen with Avodart (i.e. prevention of low-risk tumors, increased risk of aggressive tumors) are very similar to those reported previously with Proscar, a drug in the same family. This increases our confidence that the findings are a real effect and not random fluke of the data.
The story quotes an FDA document as well as an official from Glaxo. It doesn’t appear to rely solely on any press release.
Systematic, Criteria-Driven
The tale of two “negative” studies. Or, how spin is applied to make research findings look more impressive. A must read. https://johnmandrola.substack.com/p/the-tale-of-two-negative-studies
The @nytimes chose to interview one of the editors of the @AnnalsofIM (publisher of this paper) who "gushed with extraordinary glee: It’s huge! There are very few things that reduce your mortality by 30%."
Turns out coffee is not one of those few things despite all that glee. https://twitter.com/garyschwitzer/status/1533202075928215558
Comments
Please note, comments are no longer published through this website. All previously made comments are still archived and available for viewing through select posts.
Our Comments Policy
But before leaving a comment, please review these notes about our policy.
You are responsible for any comments you leave on this site.
This site is primarily a forum for discussion about the quality (or lack thereof) in journalism or other media messages (advertising, marketing, public relations, medical journals, etc.) It is not intended to be a forum for definitive discussions about medicine or science.
We will delete comments that include personal attacks, unfounded allegations, unverified claims, product pitches, profanity or any from anyone who does not list a full name and a functioning email address. We will also end any thread of repetitive comments. We don”t give medical advice so we won”t respond to questions asking for it.
We don”t have sufficient staffing to contact each commenter who left such a message. If you have a question about why your comment was edited or removed, you can email us at feedback@healthnewsreview.org.
There has been a recent burst of attention to troubles with many comments left on science and science news/communication websites. Read “Online science comments: trolls, trash and treasure.”
The authors of the Retraction Watch comments policy urge commenters:
We”re also concerned about anonymous comments. We ask that all commenters leave their full name and provide an actual email address in case we feel we need to contact them. We may delete any comment left by someone who does not leave their name and a legitimate email address.
And, as noted, product pitches of any sort – pushing treatments, tests, products, procedures, physicians, medical centers, books, websites – are likely to be deleted. We don”t accept advertising on this site and are not going to give it away free.
The ability to leave comments expires after a certain period of time. So you may find that you’re unable to leave a comment on an article that is more than a few months old.
You might also like