Lilly Discloses All Clinical Trials, Really. Except...

Good god, you people want the sun, moon, and stars from these companies, and bitch when they only get the sun and moon.

If Lilly just acquired Cialis this year, I think this is perfectly reasonable that not all of that info is up yet. I don't think the CEO was trying imply or hide anything, or being otherwise coy. I chalk this up as an innocent over/misstatement, which I think is backed up by the fact that Lilly has posted so many results on its site.

I must say that I am confused about not posting core efficacy and safety results, as I take that to mean the pivotal trials (which would already be published). While technically they may not need to post this info since it was not a Lilly product, it's probably a poor decision from a PR perspective.

It does raise the question of whose responsibility it is. In fact, from the PhRMA agreement, I would think Icos should've posted the results already.

Hi Reality,

Please go back and read the post carefully. The criticism wasn't aimed at the 15 trials that are not yet posted. The criticism was aimed at the remaining trials that Lilly has decided will not be posted at all, even though the Cialis site, which has the Lilly name on it, boasts that 22 studies showed the med was safe and effective.

Yes, this is a public relations issue, but it's also a medical issue - either info is available or not. Why will some studies be posted and not others? And why not post all studies when the company boasts about such a policy? Lilly may have only acquired Cialis this year, but has the means to agree to post the data. But the company says it won't.

Cialis may not be a controversial med, but what happens when this selectiveness is employed for a med that is controversial? Will Lilly post all trial data or not? Will exceptions be made without explanation? Are exceptions warranted, especially when a company touts a full disclosure policy?

Lilly gets kudos for initiating its registry, but that doesn't exempt the company from scrutiny or questioning. Hope this helps. And thanks for writing in.

ed at Pharmalot

Hi Reality,

Please reread the post. The criticism wasn't aimed at Lilly for not yet posting 15 trials, as we're told they will do. The criticism was aimed at the decision, which wasn't explained, not to post the remaining trials.

Perhaps Taurel doesn't know of the decision to post only some of the Cialis trials. Nonetheless, he was quite clear about transparency. Moreover, his name is on the door, so to speak, and he's out there boasting of a policy that, as it turns out, is selective. He gets the glory for successes; he should take responsibility for things that go awry or are considered questionable.

Yes, Lilly only acquired ICOS and Cialis earlier this year, but again the company has the means to post 15 trials. The company has the means to revamp the Cialis web site to ensure the Lilly corporate info is displayed. Why not at least commit to posting all trials?

And while this is a public relations issue, this is also a medical issue. Cialis may not be a controversial med, but what happens when there is controversy over a med? Will the policy be applied selectively then as well? And who benefits?

I don't mean to be argumentative. But Lilly raised this issue. And while the company should receive credit for posting as much as it does, this shouldn't exempt the company from scrutiny or further expecatations, which its own executives helped create.

As always, I appreciate that you stopped by.

best ed at Pharmalot

Is anyone really worried about this issue. I can understand the debate with kids and psych meds. But old guys with their personal issues doesn't really hit my radar as real important. Or did we stumble onto a reason you are concerned? There are an awful lot of posts on ED..... Plus the fact that there are two other PDE-5 products, I think we have ample evidence these are safe and effective products. But again, it isn't like people are required to take these to live, and honestly no matter what is discovered they could cause - is anyone going to stop taking them? I think these guys are willing to risk it. Might grow a third arm, oh well. Let's let Lilly concentrate on higher priority issues.

Have you done a medline search and looked if they are published and available to anyone who is really interested? I would, but I really am not worried about the safety of these meds and honestly have no interest to research further.

Ed,

The way I read this is that the Lilly is planning to post all of the trials it sponsored, but made the decision not to post the core safety and efficacy trials because they were undertaken by ICOS prior to its purchase. If that is the case, Taurel is still technically correct. My gut tells me that some lawyer determined that posting studies performed by Icos might somehow increase Lilly's liability.

Atlex

Pivotal clinical trials are not required to be disclosed or published. They can be submitted on a confidential basis to the FDA.

Ed, Man, I've gotta stop multitasking, sorry.

Ok call me ignorant but what makes a clinical trial Pivotal? And why would that be excluded from public view?

Hi Todd and Atlex,

I'm not suggesting there is a safety issue with Cialis. It's the broader principle that is in play.

And Atlex, you may be correct - legal may well have issued such a decision for the reason you indicated. But again, Taurel speaks of being transparent and posting all studies (emphasis on 'all'), not select studies.

Anyway, thanks to both of you for writing in.

ed at Pharmalot

Ed,

Can you clarify the details of the 5 missing trials. Are they Lilly trials or Icos trials? Do you know if they were initiated after 10/15/2002? It seems kind of vague (or I'm just extra slow today).

Laurie, The trials submitted to the FDA used in obtaining FDA approval are called pivotal trials. As with many company sponsored trials, it is up to the company whether or not they want to have these trials published. (I would doubt that legalities have anything to do with the Lilly decision.)

MY GUESS is that the Cialis pivotal trials contained a head to head study vs Viagra (or at least a Viagra arm), and that Cialis was shown to have a slightly higher incidence of certain minor side effects (e.g. perhaps backache). I would also suspect that Cialis did better in other areas.

The opthy AEs are certainly not trivial, rare as they may be (based on what we know to this point). Priapism is no joke either, notwithstanding (so to speak) how many are made about it.

Janet,

The pivotal trials were placebo controlled trials if my memory serves. In a market like this there would be no reason to do a comparitive trial especially when Cialis has the long half life advantage. As they have shown, this is significant in that it allows you to stay in the bathtub much longer and immediately captured a good chunk of marketshare.

Unless you have a markedly superior product than currently out there it is always easier to do a placebo phase 3 trial. Why have 1 more variable to go wrong.

Hi Todd - You could have a three-armed trial with placebo as one arm and Viagra and Cialis as the other two, thus it is still a placebo-controlled trial.

I disagree that there was no reason to do a comparative trial. The market was owned by Viagra, plus there were concerns regarding the long-acting effect of Cialis and whether that introduced safety issues. As a company, you might put Viagra in to see what the results might be, and make the decision later on whether or not to publish. If you can launch showing a clear advantage versus the market leader in multiple areas (not just duration of effect which does not matter to the majority of users) then you are ahead of the game. If you don't show a clear advantage, then you don't publish the results.

There has to be some reason that these results are not being disclosed. Clinical trial results that can be used for marketing advantage are typically published.

"MY GUESS is that the Cialis pivotal trials contained a head to head study vs Viagra (or at least a Viagra arm), and that Cialis was shown to have a slightly higher incidence of certain minor side effects (e.g. perhaps backache)." But isn't the point of having these trials made public so that the general population can see for themselves where the risk vs benefit ratio is better? Not presenting all clinical trials is what started the cries for public disclosure. So we are in the same boat as we were before the feel good, "voluntary participation" in clinical trials.gov. A registry that isn't mandatory serves no purpose.

Ok, to the dismay of everyone I am going to jump in with my dollars worth - much more than 2 cents below.

Does Icos know what the results would be before doing the trial? No, so why take the risk and look worse? They had a marketing advantage they were going to exploit with half life. So you get approved, have everyone assume they were equivalent and then exploit the half life advantage. I can tell you the 36 hour efficacy window is HUGE. These guys assume that means they might get "2 uses" out of their $8 pill. It is a much bigger deal than you think, and drives most of the requests from patients in this class.

So I broke down and did 3 minutes of research. Take a look at the PI on cialis.com. You get a couple of dose ranging studies looking at 5,10, and 20 mg cialis vs. placebo. There was a distinct marketing spin they could put on with the 36 hour effect. A look at the phase 2 trials shows me that it would have to be a huge (and expensive) trial to show any efficacy differences between the 2 drugs. Likely it would also show Cialis to have slightly less efficacy, but more dosing flexibility with the long half life. Also, everyone knew Levitra was on the way, so maybe a head to head trial would be irrelevant with 3 drugs in the class if Levitra ultimately proved to have the highest efficacy.

Unless you are sure you have an efficacy advantage, you are going to use placebo for your phase 3 trials. Remember, this is to put you on the market. Once you are on the market you can evaluate and decide what additional studies and indications you want to pursue.

Look at virtually any drug in the world, outside of life threating diseases (i.e. chemo drugs) and you will always see phase 3 trials against placebo. This is standard, it isn't a Lilly thing. Why would you want to do a 3 arm trial, double the cost of the study for no benefit to the company? Yes it would be great if they did it. What are you going to do with a class like the ARB's - have a trial comparing the 10+ drugs in the class, not likely.

FYI - all pivotal trial data is always presented in the PI as that is what is submitted to the FDA for approval so it will be in the labeling. So you might not have the complete trial, but it is almost always available. Again, look it up on Medline.

There is a reason docs take biostats and learn to research data in med school. It is so they understand these concepts. It is unfortunate when people jump to the wrong conclusions because they don't know what is standard and where to find the information.

I think the point of clinicaltrials.gov is so companies can't bury negative trials. I don't think it is for the average ED patient to try and do all their own research. Medicine is complicated and unless you are trained, you don't always know what you are doing.

So the information is there, just look for it. Package insert provides most relevant data, Medline fills in the holes. In my eyes there is full disclosure. You might have to have access to get the articles, and most journals sell single articles for $25. But that isn't really the companies fault.

You take the risk because you do not need to disclose the clinical trial results. Even now, all disclosure is voluntary in the industry.

While pivotal trial data is always presented in the PI, it is not necessarily ALL pivotal trial data. I happen to be aware of a specific instance where there was a Phase III trial done with 3 arms. The results for the product and placebo are in the PI, and results for the 3rd arm (the competitor) were omitted. The study remains unpublished and not disclosed by the company so your comment about the 'information being there' does not hold true in all cases.

Hello everyone,

Just to catch up. I believe the trials Lilly won't be posting on its site were Icos trials. Again, Lilly now owns the data, and benefits from the revenue derived. The ceo says all trials will be on its site in the name of transparency. Taking ownership includes taking responsibility - and following through on a vow that is, presumably, designed to remove the kind of question mark now hovering over Cialis trials.

And to Jason, full disclosure would only exist in this context if the company were to post all of the trials on its site - as the ceo says is its practice. Hunting around elsewhere may yield the same info, but that's not the same thing as Lilly posting the info on its own site.

Cheers everyone, ed at Pharmalot

Ed, We all know that Cialis and Viagra makes a man rise and shine to the ocasion.But I am more concerned withh Eli Lilly's Clinical trial results of Zyprexa in Children,trials that were conducted here in the State of Nj by Dr.Robert Hendren and UMDNJ in 2000-2001.

If Eli Lilly has nothing to hide,tell them to cough up this Study......PRONTO!!!!!

Ed,

I agree that by assuming Cialis from Icos, Lilly assumes responsibility of the results. However, I do believe that the CEO is correct in saying that they are publishing the results of all of their (Lilly's) trials. This becomes a sort of, "depends-what-is-your-definition-of-is-is" thing. Is the PR issue worth being right on technicality? That's up to Lilly to determine. I suspect Atlex is correct in that they probably (definitely) were guided by legal in making that decision. It may also be possible that there are legal details from the purchase that are in play here.

However, there is still the issue of whether these 5 trials took place before or after Oct. 15, 2002, which I'm still unclear on. If these were initiated before that date, it's a moot point.

Lisa, With all due respect (really), why do you insist on turning every post into something about Zyprexa, when there are about 100 other posts on this site specifically about Zyprexa, and at least 1 or 2 each week?

Hi Reality,

We all know how ridiculous it was to watch Clinton parse about the definition of sex a few years ago. Do we really want to watch Taurel do the same thing with the word 'all'? I don't.

All means all. There were no asterisks in his speech. Lilly owns Cialis and benefits from the revenue the product generates. And so the company owns the data and is now responsible for the drug. And Lilly says it will post all results. Anything less than posting all Cialis trials is to be selective in its policy, regardless of when any of those trials were conducted or who conducted them.

Lilly gets the rewards, Lilly should take responsibility for following through on its own policy. Agreeing with the decision to create exceptions is to give them a pass - and allow for exceptions for any number of scenarios going forward.

I would guess - although I could be wrong - that Atlex is correct in speculating there were legal reasons for this decision. I don't know. Let's say he's correct, in which case, some people may say that's a perfectly reasonable explanation. Maybe. But that still doesn't square with the insistence by the ceo that 'all' results are posted. Either they are or they aren't.

There should be no equivocation. The company made this decision to promote a better public profile - and hopefully to better inform the medical community and patients. Failing to follow through by creating exceptions undermines its own effort. I don't see any other way to interpret the word 'all' and how this policy is to be interpreted.

As always, thanks for writing in. I hope you're enjoying this little debate as much as I am.

Cheers ed at Pharmalot

Reality,

Lilly wants FDA to approve Zyprexa for children,so if Lilly believes that Zyprexa is safe and effective in children,why not disclose the data..

This Post is about Lilly and full disclosure of clinical trials,..isnt it.

But the CEO said "all of _our_ clinical trials." Those trials were not Lilly's trials. His statement is unequivocally accurate to me.

Believe me, I'm not blind to the murkier ethical issue here. If those studies took place before 10/15/2002, Lilly is absolutely adhering to the letter of the law. If they took place after that date, then things get a little squishy. There's what's what people think is "right" or is a moral obligation, and what's actually required. If Lilly is not legally bound to publish those results, I can't fully fault them.

Hi Reality,

I haven't raised in this in a legal context, merely the company's policy. Again, this is parsing. The company now owns the data - and touts all 22 studies on its Cialis web site. It has no problem boasting that the results underscore safety and effectiveness, in order to boost the bottom line. Those trials are now Lilly's trials. All is all. If exceptions and selectively is to be employed, then the world 'all' shouldn't be used to refer to studies that Lilly conducted - and also owns - for its products, especially when 'all' studies are cited to promote the products.

Cheers ed at Pharmalot

I am now understanding why pharma companies would not even try as Lilly is doing. If it is never enough, why try?

Also Janet, I would love to know your example. I always like to learn, so teach me today.

If you guys haven't figured it out, many times having data published is great for companies. I don't think they are trying to hide data, but rather they are making the lay public look using the appropriate resources just like they make physicians. If you want to split hairs on what "all" means then you win. But I am satisfied and have a feeling the majority of those in medicine are satisfied as well.

Ed,

I misused the word "legally"; that was really in reference to the PhRMA agreement.

I totally get what you're saying and I do see how Lilly is having it both ways -- promoting the 22 studies but only posting ~17. But Lilly and other companies have agreed to certain posting/publishing requirements, and if they're following that, I can't really criticize them.

I do disagree with the "all is all" part with regard to what the CEO said and the studies that Icos conducted. To me, that falls more on the factual side of the fence than the parsing side of the fence. By assuming Cialis, those studies don't become Lilly's -- to me, they're still Icos' studies.

Hi Jason, and Reality,

This discussion reminds me of an old expression: 'Say what you mean, and mean what you say.' If Sid meant anything less than 'all,' he should say so. And again, Lilly owns Icos, Lilly owns Cialis, Lilly owns the trial data, Lilly owns the profits. With ownership comes responsibility.

Cheers, again, ed at Pharmalot

And I'm reminded of expressions such as, "no good deed goes unpunished."

What can I say, I disagree that those studies become Lilly studies. Even if they now own the data, those were clearly not Lilly's studies. They didn't design them and they didn't conduct them. Taurel said "all of OUR studies." I don't think that's parsing -- I think those are the simple facts.

I suppose we'll agree to disagree.

While we're at it, 'caveat emptor' is a good one too. When Pfizer acquired Parke Davis it got Neurontin, a good drug that happened to have been widely used off-label. Along with the big sales came a fine of $240m which Pfizer paid as the then new owner of the problem. So I suppose the owner of an acquired company owns the lot, data, sales, previous studies and all the headaches and responsibilities that come with ownership.

Chris & Ed--

I think you are spot on. All is all . . . how much more straightforward can you get? When you want to include enough adjectives to destroy a definition, what then is the purpose of the original declaration? PR? While Reality allows Taurel a 'loophole' because of the inclusion of the word "our" . . . he would surely agree that when Lilly bought Icos/Cialis--Lilly bought the whole package--the R&D, the trials, the marketing statistics/strategy. To somehow rely on semantics to cherrypick what information is "ours" reflects the same sort of "integrity" that is responsible for the growth of consumer cynicism we are now experiencing.

Hello again,

Reality - yes, I would agree to disagree. I understand your point, but Lilly own's the studies and can post them. So... But thanks for going round on this one. It is interesting, isn't it?

And Chris, my thought is one takes the good with the bad, or vice versa, if the glass is half empty.

Thanks to you both, and everyone else, for such a lively discussion.

ed at Pharmalot

I guess I am using knowledge I gained in 11 years of happy marriage.

1) always agree 2) pick your battles

I think #2 applies with missing Cialis data that could be found with 3 minutes of medline searches. If you are taking him literally, and want to hold him to it that is certainly your POV and right. I am just saying practically speaking I am pretty sure there are things of higher importance.

Hi Jason,

I understand your point. I agree there are meds of higher importance over which to raise this issue. As I see it, the issue isn't Cialis - it's the fact that exceptions are made when convenient. And so the door opens to such thinking in the future toward other drugs. Anyway, I'm not trying to pick a battle; I was highlighting what I see as an interesting example of doing one thing and saying another.

Cheers ed at Pharmalot

What did Lilly say when you contacted them about the missing trials?

Also Janet, if you are still there, what is your example?

This is lame. I cant believe everyones making such a big deal over this. People need to get a life. Lilly was obviously trying to be proactive and do right by posting all their trials. Yeah, so what... cialis doesnt have all posted...and it wasnt acquired by them until recently. who cares. but back to what others posted... is everything posted for zyprexa? or cymbalta? those are 2 that should have all the data there.

Hi Robert,

With all due respect, perhaps you're missing the point. The issue is the policy toward posting all trials, as articulated by the ceo, not just Cialis trials, in particular.

Cialis, as it turns out, is an example of where the company wants it both ways - touting the safety and effectiveness off 22 Cialis trials on its Cialis web site, and boasting that 'all' trials are posted on its corporate site, per its policy, while then making exceptions for unspecified reasons for a handful of Cialis trials, which apparently will never be posted.

What if one were to substitute Zyprexa or Cymbalta for Cialis in the scenario detailed in the original post? Then, it appears, that would gain your attention.

The issue is the policy - its true intent and how it is applied. If Lilly were to make exceptions for Cialis trials, then perhaps, it may be still easier for exceptions for Zyprexa or Cymbalta trials, or any other trials.

In essence, this is a Pandora's box. I hope this explains why so much chatter has evolved over this issue, and why Cialis trials may be emblematic of the greater concern.

Thanks for stopping by,

ed at Pharmalot

Jason--

You may be the caring, workaholic doctor you self-describe . . . long hours overseeing the health of your patients. You also seem quick to deride lay people for their lack of your superior education, years of training, and ability to interpret scientific literature. (Obviously, you believe that the lack of M.D. after our name precludes us from interpreting and understanding complicated medical issues.)

Dr. Roy Poses, at the Healthcare Renewal blogsite, just posted an article titled: Physicians "Learned Helplessness" at http://hcrenewal.blogspot.com/2007/10/physicians-learned-helplessness.html#links

This is the view that some of us have of physicians in general. You may be an exception . . . if so, I applaud you. Nevertheless, Poses speaks for many of us as he paints his picture of the current reality that has been birthed when a powerful industry with megabucks directs the course of science and medicine.

Lilly's current PR event--posting clinical trial information--must be viewed with a jaundiced eye. I recently spent a bit of time reading their rDNA insulin-approval application (from the early 1980s). It was rife with cherry-picked protocols; ignoring/downplaying AEs; and promoting the benefits (of which I could find none). They have merely gotten better at these techniques over the years, and their "new" spirit of transparency rings hollow. (I'm still waiting to see the results of the FDA-required completion of clinical trials re: rDNA insulin.)

Lisa has a key point about Zyprexa trials for children. After all, the drug is the most lethal atypical, and just putting new warnings on the label after all these many years does not the drug fix.

There has been much chatter over the years that the original Zyprexa trials were "doctored". There is serious reason to find out what happened with the children, and keep this lethal drug from FDA approval. Of course, then there's such extensive off-label use, it would help the situation if Zyprexa was not approved for children....one possible way to cut down on devastating side effects.

Best solution: Take the drug off the market, which should have happened long ago. Come on, FDA. Do your job.

Ellen- Can you prove that Zyprexa studies were "doctored?" If you make that claim, you better have evidence (and quoting one of Lisa's or another loon's website does not suffice).

Ed,

What was Lilly's response when you contacted them to ask?

I assume as a journalist you did that, what was the response?

Hi Jason,

Yes, I reached out. And the response is right there in the post, next to the picture of Cialis. I kept pressing for an answer beyond this written response, and the fellow woud only say that a decision was made.

Hope this helps, ed at Pharmalot

Bob, (and quoting Lisa or anothers loon's website does not suffice)

From the tone of your post, Im assuming that you forgot to take your antipsychotic medication today.Compliance means sound Mental Health....

Ellen,

For those of us who are sane!...You can read one of the Clinical Trials of Zyprexa in children.Hat Tip goes to New York Times Reporter Alex Berenson....

http://www.clinicalstudyresults.org/documents/company-study_2210_0.pdf

Best Wishes, Lisa

Lisa,

Come on, how about a hat tip this way -- I've mentioned that site at least half a dozen times!

As for the study itself, seems like a very positive study from an efficacy point, and a concerning, if unsurprising study from a safety standpoint given what we know about Zyprexa. Actually, of all the AEs, the most concerning, which I don't think I've heard much about, was the increase in systolic BP (+3.61 mm Hg).

Of course, the patients receiving placebo had a statistically higher rate of abnormally albumin levels (p

Repost -- I forgot this site doesn't like less-than signs! (Note to Ed)

Lisa,

Come on, how about a hat tip this way -- I've mentioned that site at least half a dozen times!

As for the study itself, seems like a very positive study from an efficacy point, and a concerning, if unsurprising study from a safety standpoint given what we know about Zyprexa. Actually, of all the AEs, the most concerning, which I don't think I've heard much about, was the increase in systolic BP (+3.61 mm Hg).

Of course, the patients receiving placebo had a statistically higher rate of abnormally albumin levels (pless than 0.001), which just goes to show, that sometimes weird things happen in trials.

But hey, now we know Zyprexa works in adolescents with bipolar.