Terra Sigillata

While the coffee wasn’t quite ready this morning, I ventured to the Wall Street Journal health page at the Wall Street Journal, one of my frequent first-reads.

I was immediately intrigued by a short article from the excellent Jennifer Corbett Dooren about Roche-Genentech gaining US FDA approval for a new rheumatoid arthritis drug, Actemra.

Actemra (tocilizumab) is a monoclonal antibody that works via a novel mechanism of blocking the receptor for interleukin-6, a pro-inflammatory molecule called a cytokine. What is most important is that Actemra appears to work in patients who have not been helped by other existing drugs such as those like Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab) that block the effects of another cytokine called TNF-alpha.

Rheumatoid arthritis is not just joint aches and pains. It is a very serious disease that can cause not just pain but deformity and progressive disability. Rheumatoid arthritis afflicts 1.3 million people in the US.

But what caught my eye and generated my pre-caffeine ire was in the opening sentence, terminology used in clinical pharmacology and therapeutics, words that I admit to have even uttered myself:

WASHINGTON–The Food and Drug Administration Friday approved a new type of drug by Roche Holding AG’s Genentech unit to treat rheumatoid arthritis in patients who have failed other treatments. [emphasis mine]

I know that we use that phrase because it is seems less cumbersome than saying, “in patients whose disease has not responded to existing drugs.”

But saying that the patient failed the treatment makes it seems that the patient somehow bears responsibility for the lack of their disease to respond to the tools we currently have available. Yes, yes, I know – disease is essentially a patient’s own pathophysiology, where their own homeostatic mechanisms are awry or respond inappropriately to environmental changes or invading organisms.

But jeez, have you ever thought what it sounds like to a patient to hear that they failed the therapy? Could we possibly take any less responsibility for our failure to treat disease? Even if physicians want to use the word “fail” couldn’t they at least shift the blame to us basic scientists who’ve failed to come up with an alternative drug?

As I’m writing this and searching for literature on the medical psychology of using this term, I just realized why I am bothered. If we accept that medicine says, “the patient failed the treatment,” that’s one thing. What troubles me is that I just read the statement in the opening sentence of an article in a highly-regarded business publication crafted by a health and medicine writer whom I respect.

Don’t get me wrong. I’m all for personal responsibility in health. All of us could do a better job of watching what we eat, exercising more, not smoking, drinking alcohol in moderation – the big four factors that could make a greater impact on human disease than the next new wonder drug.

But just because a $10,000/year drug doesn’t work for me and my rheumatoid arthritis, does that really mean that “I failed the treatment?”

I know we’ve got some medical sociologists and psychologists out there reading – I’d be grateful for any commentary or direction to scholarly literature on why we continue to use the term, “the patient failed the treatment.”

One final note
As an amorphous descriptor, Big Pharma has certainly lost a lot of trust of the general public and the scientific community over the past several years from data cover-ups on drug-related deaths to ghostwriting of peer-reviewed journal articles, the latter of which was eloquently addressed by Orac last year. These practices are inexcusable and deserve strong punishment, especially where it is clear that loss of lives was a result of deceptive clinical data submission.

I’ve had the pleasure of training with many outstanding scientists who now work in the industry and, particularly in the field of pharmacology, have come to respect and learn from new colleagues who’ve chosen industrial careers. Several of these people are among the most ethical I know and, as with any other industry, are pained equally if not more by the scandalous cases.

So when good things happen, such as the approval of a new drug that has the potential to help people in pain for whom no other agent has helped, I like to acknowledge the efforts of those folks behind the work.

Let me offer my heartiest congratulations to colleagues at Roche and Genentech on this nail biter after having been asked for more data last year. Addressing these kinds of scientific and regulatory challenges gives me great respect for my colleagues at the bench and in the clinic who have worked to relieve human suffering from this debilitating disease.

Comments

#1 biochem belle
January 9, 2010

A very interesting question. I know nothing about psychology, but it certainly seems a strategic turn-of-phrase. As you point out, it shifts the focus off the drug and onto the patient. Instead of creating the question “Why didn’t the drug work?”, it poses the question “Why is this patient different?”. From the standpoint of drug development, I wonder if the phrase is chosen to create a specific connotation for investment and regulatory considerations.

Of course, it could just be a matter of pride. We see similar phrase usage in basic research, as well. We never like to say that our hypothesis was wrong or that our design failed. We much prefer to distance ourselves from failure.
#2 Orac
January 9, 2010

God, I hate that phrase “the patient failed treatment.” I never use it. What I say instead is that the treatment didn’t work in that patient.
#3 Tamara
January 9, 2010

I would think the term would be legitimate when applied to concompliance, perhaps. I would say that as a twelve year old I failed the treatment for malocclusion by not consistently wearing those blasted rubber bands.

Tamara
#4 biochem belle
January 9, 2010

@Tamara: One could argue that it is an appropriate term in the context of noncompliance. In this case, however, the drugs (including the “failed” ones) are monoclonal antibodies, which are administered i.v. in the clinic, so physicians have a precise, accurate measure of patient compliance.
#5 Reggie
January 9, 2010

As a patient, I can tell you that the language is unfortunate. It’s so pervasive that I slip and use the word “failed” myself sometimes. Neither the patient nor industry fails when a particular biologic (most for RA are around $20,000 per year) isn’t effective for an individual patient. Both will go forward in search of the next solution.

Patients are described by physicians as having a “chief complaint.” Or the patient “denies” abuse of alcohol. The patient “claims” to be compliant. And so on. God help you if you become a “difficult patient.” Reading one’s own medical record for the first time can be quite demoralizing!
#6 John
January 9, 2010

Good point.. but this is part of the usual politic of blaming the patient and it is a matter of pride..
#7 derek
January 9, 2010

patients who have failed other treatments. [emphasis mine]… I know that we use that phrase because it is seems less cumbersome

What’s wrong with “patients other treatments have failed”, or “where other treatments have failed”?
#8 Tsu Dho Nimh
January 9, 2010

Pharmboy – maybe her words were the victim of a clueless editor.

If you don’t like the phrase, write her and point out to her what you are pointing out to us here.
#9 Abel Pharmboy
January 9, 2010

Good point, Tsu Dho Nimh – I’ll do that.
#10 MitoScientist
January 9, 2010

I have to say, as a grad student who wants to continue on in industry, I think its quite important for scientists with good heads on their shoulders to be in industry. If for nothing else, to try and do their tiny part keeping these companies honest (relatively speaking, of course).
#11 WarmSocks
January 9, 2010

Bravo! Patients do not like hearing that they failed when it was really the medication that failed. Thank you so much for noticing that there is a distinction.
#12 Gaythia
January 9, 2010

Sometimes nobody failed. I’m dealing with elder care issues. The phrase I don’t want to hear is “failure to thrive”. In this situation to be or not to be IS the question. The possibility exists that bad things might happen despite best efforts on all sides or even in the case of reasonable efforts given the circumstances. This is true for the patients, the hands-on medical practitioners and even the more indirect pharmacists or lab workers. It is not always possible to define “bad” let alone try to assign failure.
#13 Abel Pharmboy
January 10, 2010

I’m glad to see that Orac hates the phrase too because its in our field of oncology that I see it used the most.

Gaythia, that’s another very notable point. I’m beginning to think that “failure” is simply a more concise term for medical use but it is just so loaded emotionally. We could do better.

I’ve asked Ms. Corbett Dooren for her impressions on Tsu’s recommendation but I also thought I’d check the original Genentech press release to see if the phrase was there. While one of the trials had the word failure as part of its acronym, the company described the patients in the first paragraph as those “who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.” So, kudos to the writers of Genentech press releases.
#14 Not as easy as it seems
January 10, 2010

Just a note of correction- it was the clinical and regulatory professionals at Roche USA who brought ACTEMRA to market. The drug is being launched by Genentech as a result of the merger of the two companies, but this was a Roche USA effort all the way.
#15 Gaythia
January 10, 2010

I recommend following the link to WarmSocks blog (see #11 above) to see how it feels as a patient to be told that they “failed” a treatment. Also this blog eloquently describes the financial impact of a major health issue on a family.

Our health system has many shortcomings as well as many positive attributes.

Warmsocks, I wish you and your family well.
#16 Karl Withakay
January 11, 2010

I’m not a medical professional, but I’ve mostly heard one of the following:

“in patients for whom other treatments have failed.”
or
“in patients for whom other treatments are not effective”

So the insensitivity is not universal.
#17 Keith Robison
January 11, 2010

“patients whose disease has vanquished other treatments”?
#18 brook
January 11, 2010

By definition “fail” means the subject of the verb has fallen short. One of the meanings, “failing health”, doesn’t have the connotation of willfullness, but the other meanings explicitly talk about deceit, inadequacy, lack of success.

I think you’re right to think about the appropriateness of the word. Many better terms have been suggested.

One of my kiddos ended up in NICU. Flipping through the chart I noticed that it read “Patient admitted after failed homebirth” I give the NICU director a lot of credit for deleting that passage after I pointed out that this patient would have ended up in the NICU no matter where labor started. (And since kiddo was fullterm, 9lbs this was a standard procedure kind of deal nobody had failed anything.)
#19 Stolen Dormouse
January 12, 2010

As a senior editor at the Journal of the National Cancer Institute< \i>, our editor-in-chief made a point that we should never accept “patient failed the treatment” in the articles we accepted for publication. He also made a point that results can be statistically significant without being clinically significant. I’ve kept both points in mind ever since.
#20 Stolen Dormouse
January 12, 2010

Sorry for the HTML error. My comment should have read:

As a senior editor at the Journal of the National Cancer Institute, our editor-in-chief made a point that we should never accept “patient failed the treatment” in the articles we accepted for publication. He also made a point that results can be statistically significant without being clinically significant. I’ve kept both points in mind ever since.
#21 Stolen Dormouse
January 12, 2010

As a senior editor at the Journal of the National Cancer Institute, our editor-in-chief made a point that we should never accept “patient failed the treatment” in the articles we accepted for publication. He also made a point that results can be statistically significant without being clinically significant. I’ve kept both points in mind ever since.