329

You've probably seen it already, but if you haven't, please read it:

Restoring Study 329: efficacy and harms of paroxetine and
imipramine in treatment of major depression in adolescence

It's been eagerly anticipated, and everyone pretty much guessed what the conclusions would be, but it's finally official. The data from Study 329 show that paxil improved depression in adolescents no more than placebo (same for imipramine).

More importantly, from my perspective, since there are always some outliers who respond to meds others don't, are the adverse events. The re-analysis showed a lot more harm than the original. Paxil had a lot more psychiatric adverse events, such as suicidal behavior, and imipramine a lot more cardiovascular events.

Results
The efficacy of paroxetine and imipramine was not
statistically or clinically significantly different from
placebo for any prespecified primary or secondary
efficacy outcome. HAM-D scores decreased by 10.7
(least squares mean) (95% confidence interval 9.1 to
12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points,
respectively, for the paroxetine, imipramine and
placebo groups (P=0.20). There were clinically
significant increases in harms, including suicidal
ideation and behaviour and other serious adverse
events in the paroxetine group and cardiovascular
problems in the imipramine group.

The reasons for the discrepancies are interesting. It seems like the difference in efficacy results was related to the fact that the original authors deviated from protocol, so that the same data give different results:

The marked difference between the efficacy outcomes as reported by us and those reported by SKB results from the fact that our analysis kept faith with the protocol’s methods and its designation of primary and secondary outcome variables.

The authors/sponsors departed from their study protocol in the CSR itself by performing pairwise comparisons of two of the three groups when the omnibus ANOVA showed no significance in either the continuous or dichotomous variables. They also reported four other variables as significant that had not been mentioned in the protocol or its amendments, without any acknowledgment that these measures were introduced post hoc. This contravened provision II of appendix B of the Study 329 protocol (“Administrative Matters”), according to which any change to the study protocol was required to be filed as an amendment/modification.

The difference in adverse events had to do with how the events were coded. The original article used a now obsolete and unavailable coding system, and the language in the Case Study Reports (CSR's) was often translated to something innocuous. I particularly liked one table which showed the ways that adverse events could be inaccurately reported:

As for GSK's reaction, the NY Times included this quote from the original authors:

Dr. Keller and his co-authors strongly disputed the reassessment of their work. In a joint statement, he and his team said they incorporated secondary measures before knowing which patients were taking Paxil and which were not — not afterward, as the new analysis claims, for some of the measures. “In summary, to describe our trial as ‘misreported’ is pejorative and wrong,” they conclude.


The authors of the new study, Joanna Le Noury, John M Nardo, David Healy, Jon Jureidini, Melissa Raven, Catalin Tufanaru, and Elia Abi-Jaoude, had their work cut out for them:

This RIAT exercise proved to be extremely demanding of resources. We have logged over 250 000 words of email correspondence among the team over two years. The single screen remote desktop interface (that we called the “periscope”) proved to be an enormous challenge. The efficacy analysis required that multiple spreadsheet tables were open simultane- ously, with much copying, pasting, and cross check- ing, and the space was highly restrictive. Gaining access to the case report forms required extensive correspondence with GSK.12 Although GSK ultimately provided case report forms, they were even harder to manage, given that we could see only one page at a time. It required about a thousand hours to examine only a third of the case report forms. Being unable to print them was a considerable handicap. There were no means to prepare packets for multiple independent coders, to decrease bias; to make annotations or use margin comments; or to sort and collate the adverse event reports. Our experience highlights that hard copies as well as electronic copies are crucial for an enterprise like this. 

I think they deserve huge thanks.

So check out the study. And also check out Study329.org for the whole history, as well as multiple posts by authors Mickey Nardo at 1boringoldman.com and David Healy at Davidhealy.org and Rxisk.org.

My ICD-10 Bad

I recently posted about ICD-10, with a link and a widget and whatnot. Most of what I posted is still valid, as far as I know. But I got a message today from the same friend and colleague who sent me the original link, about an email she received from the state:

Claims should not contain both ICD-9 codes and ICD-10 codes. Claims that are billed with both ICD-9 and ICD-10 diagnosis codes on the same claim may also be considered unprocessable. Therefore, services rendered prior to October 1, 2015 should be billed separately than services rendered from October 1, 2015 forward.

So I'm going to take the ICD-10 diagnoses off my September bills, and the ICD-9 diagnoses off the October bills. I'm guessing the insurance companies will be confused, but at least they won't be able to say I didn't do what they asked.

Remember: 9 through 9 (September), and 10 starts in 10 (October).

And big thanks to Susan.

ICD-10, Comin' At Ya

A friend and colleague sent me a little present-a link to an online ICD-9 to ICD-10 converter.

The site is AAPC.com, and I couldn't figure out what, exactly, AAPC stands for, but as far as I can tell, it's something like, American Association of Professional Coders, and it offers training and certification in medical coding and billing, among other things.

The above link also has a countdown timer to October 1st, when ICD-10 coding will be required.

I've posted previously about ICD-10, (and there's still the page link up at the top of my blog with common diagnoses conversions). There seems to be a lot of fuss about the conversion, but I don't think it's going to be that big a deal in psychiatry. I think there is a much more manageable number of codes than in, say, internal medicine, so I'm not too concerned. What I've been doing about it, lately, is starting to include ICD-10 coding in my charts, and on this month's bill. But I'm also retaining the ICD-9 coding on the bill, for the time being, because I think it's going to be a while before the insurance companies get things figured out, and with both codes, they don't have an excuse not to reimburse.

So my bills say something like:

Dx: ICD-9  296.30; ICD-10  F33.9

Hopefully, that'll work out okay.

Incidentally, what I mean by including ICD-10 coding in my charts is that I handwrite the ICD-10 code on the inside of a patient's folder, i.e. physical chart, right under where I've handwritten the ICD-9 code. Sometimes low-tech is a good thing.

I asked the friend who sent me the link if I could post it, and she, in turn, asked the person who sent her the link, who wrote back that I could post it, and who wished to have her information listed in this form:

Rachel T. Greenwald, Ph.D. of RTG Billing, telephone (347) 980-2417 and email rachel@rtgbilling.com.

I'm trying not to do anything shady in this, but it seems to be a free site, open to the public, and it was a nice gesture. So I hope that turns out okay, too.

And in case you haven't noticed, I put an ICD-9 to ICD-10 converter widget, which I got from the AAPC site, at the top of the column to the right. I tried it out, and it takes you to the site, rather than just giving you the code right in the widget, so I may take it down at some point. But right now, with the conversion imminent, I consider it a public service.

Addendum:

See also, My ICD-10 Bad for a correction.

Bipolar Image

A reader kindly sent me a link to a research graphic on bipolar disorder that she helped to create, from a site called, "TopCounselingSchools.Org", which provides information about degrees available in counseling. I know nothing about the site, but I liked the image, so I'm sharing it with you.

The Highs and Lows of Bipolar Disorders

It's a really nice graphic. Visually appealing, not glaring, not too much information in one place, nothing blinking at you, information organized into clearly defined sections, just enough information to get you started, provides its sources. I can't vouch for the stats, but they seem about right.

The whole image is too large for this post, so here's a piece of it:

The one thing I found confusing is that in the first section, there's this:

It's one of several general statistics in that section.

Then, in the next section, there's this:

The American statistic above is one of the first you come across. By the time I got to the second section, I'd forgotten that I'd already read the stat for America, and I started looking for it, and was confused when I couldn't find it. I eventually (like 10 seconds) figured it out.  The only thing I'd change would be to repeat the American figure with the others in this section, since the type of display is different from the original one. This is really just me being fussy and weird. It's a great graphic.

So check it out.

And thanks to the reader who sent it. I don't know if she wanted her name listed or not, so if she does, I'll update this post.