Grassley Critic Fails The Full Disclosure Test
72 CommentsBy Ed Silverman // May 29th, 2008 // 5:37 pm
In an impassioned editorial in The Wall Street Journal this morning, former FDA medical officer Mark Thornton lashed out at Chuck Grassley, the ranking Republican on the Senate Finance Committee, for asking the General Accountability Office to launch an inquiry into whether the FDA was correct to grant accelerated approval for Genetech’s Avastin cancer med. The move, he wrote, “will have a catastrophic effect on America’s ability to develop new drugs.”
At issue is whether the FDA should use surrogate endpoints as the basis for approval. That’s what the agency did three months ago by rejecting an advisory panel recommendation and approving Avastin for metastatic breast cancer. Tests found the drug slowed tumor growth, even though Avastin wasn’t shown to extend life. As Thornton wrote: “…if all cancer clinical trials were required to show a survival benefit from the get-go, progress in cancer-drug development would slow to an absolute crawl.”
“…The damage done by Mr. Grassley’s decision to make an issue of this decision cannot be understated. Having served at the FDA during the Congressional hearings over the Imclone/Martha Stewart insider trading scandal, I can attest to how an action like this GAO inquiry will resonate within the halls of FDA. An extremely cautious and protective bureaucracy will respond to such intimidation by being even more protective…”
“Cancer-drug development stands on a precipice overlooking a new dark age in which each new product’s development is longer and costlier than the last. Companies may decide it is not financially viable to even bother developing new drugs, and the pipeline for new products to treat cancer could slow even more. Mr. Grassley’s legacy could be thousands of additional cancer deaths.”
Whether Thornton, who worked in the FDA’s Office of Oncology Products and now volunteers as president of the Sarcoma Foundation of America, is correct remains to be seen. But he forgot to write one thing - he is also senior vp of clinical development at GenVec, a small biopharmaceutical whose lead candidate would treat - you guessed it - cancer (see page 13 of the latest SEC filing). Why that wasn’t disclosed is unknown. Thornton has not yet returned messages.
condor
Well, now — W H A M ! — that one, Ed, it had some real stank on it!
This is priceless — Thornton also said “cannot be under-estimated” when he plainly meant cannot be “OVER-stated. . . .” Heh!
[". . .The damage done by Mr. Grassley’s decision to make an issue of this decision cannot be understated. . ."]
This is a truly great piece of journalism. Well done.
Justice in Michigan
Condor - Well, if it can’t be overstated, it can’t be understated either, right?
Well, maybe it could. If you went to the end of a very large field, turned into a strong wind, and quietly whispered “Peril exists” (to quote Andy Van E) that might be understatement…
hockeystick
There is even more: “Mark O. Thornton MD, MPH, PhD has been Senior Vice President of Clinical Development of GenVec Inc. since October 2006. [...] Dr. Thornton serves as Director of Excel Tech Ltd. Dr. Thornton serves as a Member of the Medical Advisory Board of Ziopharm Inc. and serves as Member of Advisory Board of Ziopharm Oncology Inc. ”
http://investing.businessweek.com/research/stocks/people/person.asp?personId=11715801&symbol=GNVC.O
condor
I meant to use “-stated” in both of mine, above — my bad.
But very funny, JiM!
Heh.
Thom
I wonder if Mr. Thornton is wishing he’d never popped off at the mouth. Especially since his company gets some federal grant money from the NIH.
Adam Feuerstein
Mark Thornton is absolutely right, whether his employment with GenVec was disclosed or not. I’m all for crusading Senate do-gooders, but in this case, Grassley has veered off into moron land.
The use of surrogate endpoints to approve cancer drugs is perfectly legitimate and the approval of Avastin in breast cancer was the right thing for the FDA to do.
That, it seems, is the real issue, not whether Thornton disclosed his employer or not. Wow, he works for a drug company. Shocking! If that’s all you’ve got to work with to counter Thornton’s argument, you’re woefully weak-handed.
Sul
OK…so these pharma companies have a guy with an MD, PhD and an MPH. He’s worked in the public sector as well right? Obviously cancer research and advocacy is his passion or he wouldn’t devote so much time and energy to it…even before he went semi-private sector. Everyone wants full disclosure. Does it make him a bad person where his opinion is moot or tainted simply because of his employ? Seriously, journalists need to take a hard look at themselves as well. Holier than thou garbage like this makes me question your integrity as well. I believe that those that find the most fault usually have the most guilt!
CMC guy
Adam Feuerstein is on target as the content of Thornton’s piece is what is important and agree that Grassley approach can be damaging to drug development. Surrogates can be valuable endpoints (and misleading in cases too) and my understanding anything granted approval on such do mandate additional studies to then prove benefit in disease treatment (similiar to EU conditional approval which has more formalized staging).
Most the mania with full disclosure is over blown IMO. Editors and sponsors are responsible for setting appropriate levels and should be based on context and intentions. There may be arguments for including more info on authors and others on occasion but unless you are going to post complete CVs, financial statements and associates on everyone then potential sources of conflict can never be clear. For instance I have a brother in Aerospace so do I need to claim that if I promote idea that airlines should replace their aging fleets. I think it is also detrimental view as the best people with skills and knowledge are likely to have connections that might be perceived as conflicts however I also believe most people can act with integrity and will remove themselves if circumstances dictate.
dmcrane
I agree the content of the Thornton piece is the important thing. My boyfriend has pancreatic cancer and the last thing we need is someone like Grassley slowing down the forward movement of development of new cancer drugs. Avastin has been found to be wonderfully effective for certain cancers, and even though pancreatic cancer is not one of the, I applaud the fact that each new drug buys many people some time and sometimes their life. We are just buying time here, trying to keep him alive until researchers find the magic bullet that cures his cancer. Grassley wants to play with cancer victims’ lives, and his nonsensical proposal will do nothing more than slow the process until many people run out of time.
Ed Silverman
Hi Adam, Sul and CMC Guy,
Thanks for your notes. Just to be clear, if you look closely at what I wrote, I didn’t question Thornton’s premise. So please take a moment to go back and look.
As I indicated, whether he is correct about Grassley’s effect on the FDA remains to be seen. I didn’t support his argument and I didn’t criticize his argument. Nor did I support or criticize Grassley’s actions. With all due respect, you’re off base if you think otherwise.
As for disclosure, my view is that more is better than less. In that way, we may have some context in which to understand what informs the views of an editorial page writer, a physician writing a medical journal study or an advisory committee member, or whoever else you care to name.
In this case, the disclosure that he has a senior level job at a company developing a cancer med may have convinced some people that he is a particularly qualified expert, while others may have carped that he is only looking out for himself. That would be up to the reader. But at least we would all have the benefit of the knowledge.
Whether we like it or not, the lack of disclosure has been an issue for the pharma biz for the last few years. I think Thornton made a useful contribution to the wider discussion about the standards for drug approval, which is an important topic and one that I have written about on this site in the wake of the Avastin approval.
But if we are going to have full discussions, it would be helpful to better understand the positions of those involved. In this case, the absence of his employment is a curious omission. And had the one extra bit of pertinent info been listed, we wouldn’t be having this discussion, which detracts from the larger issue raised.
It’s in that spirit - not a ‘holier-than-thou’ attitude - that motivates to say I believe disclosure is actually helpful. We can all focus on the matter at hand. And that would be a good thing. Your thoughts?
Meanwhile, thanks for writing in,
ed
Thom
Can any of the critics on here point out where Grassley was against the approval of drugs based on surrogate endpoints? If you bother to read what he requested from GAO, you’ll find that he asked the GAO to see if FDA was requiring the follow up safety studies AFTER the drug is approved based on surrogate endpoints.
First read. Then think. Then write.
Paul
Does that automatically negate his arguments?
I don’t think so; I think his editorial is spot on. Had he disclosed it would not have been a difference to me; it’s not like he’s reporting on his work paid by the company; he’s expressing his opinion and it happens to be sound.
Let’s read it carefully and decide if indeed Grassley’s office is doing no more than posturing and politicking with a new issue every single week.
Nathan
I’ve got to concur with some other comments above: Ed, you are making too big of a deal of full disclosure. That was a great article - until you got to the last paragraph. Full disclosure is important to JOURNALISTS like yourself. It’s important so that you can appropriately judge what the facts and motivations are. But it’s not important to most readers. It’s up to YOU to decide what the facts are here. If you think that Thornton’s role at a biotech company taints his view, then have some balls and come out and say so. If you don’t think it taints his view, then just don’t say anything. The last paragraph takes the thunder from the remainder of the article and transforms it to a little whimper. What was a great article now is likely to have little impact on a typical layperson simply because of a couple of sentences.
Nathan
By the way, it doesn’t take a rocket scientist to figure out that Thornton is absolutely correct. Eliminating surrogate endpoints in cancer research would add easily 3-5 years on pivotal clinical trials, making the drugs more expensive to develop and shortening the patent protection period. This is a STRONG disincentive to do research in this area.
If you doubt this, just take a look at what has happened to antibiotic research. There is essentially no antibacterial research going on in big-pharma. Why? Thousands and thousands of people die every year from bacterial infections! It’s because the barrier has now been set too high and it doesn’t make FINANCIAL sense to do research in this area. What a shame it will be if the same thing happens to cancer research.
Mark Thornton
Dear Mr. Silverman,
I received your voice message after arriving in Chicago last night for ASCO. I was not ignoring your inquiry as you imply in your article.
My advocacy is based on doing everything possible in the fight against cancer on behalf of my son, who is a 10 year sarcoma survivor. This includes orienting my career in clinical research over the last 8 years towards cancer drug development. The piece was written from that perspective and knowledge, and called on my experience while at the FDA.
I saw no need to mention my employment with GenVec, principally to protect them from having people think that somehow the company supported my personal views. I am sorry if this has been misconstrued as having hidden something. I appreciate the deep suspicion everyone has about seemingly everything these days. If it helps you to dismiss this crisis due to your discovery, the that is unfortunate.
Sincerely,
Mark Thornton, MD
President
Sarcoma Foundation of America
Ed Silverman
Hi Nathan,
Somehow, you missed my point. As I indicated in my last comment, in general, more disclosure is better than less - and that should apply to all discussions, because there may be instances where it is important to one person but less so to another. Sometimes, though, you may find yourself to be the person who wants more disclosure than the next person or vice versa. But which standard should apply - one that is defined by one only person’s interest in the topic?
I deliberately didn’t suggest his view was tainted - I wanted to leave that to readers/viewers to decide. As I also indicated above, some may find his job to qualify him further to express that view, while others may think he’s got his own best interest at heart before anything else. I put it out there for discussion because, as I noted, disclosure is an issue.
And - again - I took no position on the debate over the use of surrogate endpoints or Grassley’s request of the GAO to follow-up whether follow-up studies were conducted. Essentially, I’m repeating myself because you somehow believe I was making a judgement when, again, I wanted to point out an omission that - to some - may have been useful info to have when weighing an opinion and what motivates the opinion.
As always, thanks for stopping by,
ed
Ed Silverman
Hi Mark,
Thanks for writing. First, I didn’t write that you were ignoring me. I wrote what I knew at the time - messages weren’t returned. But I’m glad you responded. Direct replies are always helpful.
As to the omission of your employment, for all the reasons I’ve stated in my previous two comments, I continue to contend more disclosure is better than less. I understand your explanation, but in this day and age, a fuller view of what informs one’s opinions is appreciated, particularly when a direct benefit may be involved from the position that is being taken.
Again, if you were to read my previous comments, I didn’t make a judgement about your position - or Grassley’s interest in seeing the GAO probe whether the FDA ensured that follow-up studies were conducted. So no, I didn’t ‘dismiss the crisis,’ as you put it.
Although you’re a volunteer at the Sarcoma Foundation, you listed that but this editorial was a personal view, as you indicated, and doesn’t represent the foundation in that case. So why is it okay to identify yourself with the foundation and not the company?
If you want the issue to be discussed openly, I would suggest you put your cards on the table and let them fall where they may. In all fairness, some people may believe your position at GenVec further qualifies you to write what you did, while others may choose to think your view may also be motivated, in part, by self interest. Why not let the reader decide? If the issue is that important and your view is valid, then perhaps they will come around, regardless of your affiliations.
This is basic stuff. For anyone to suggest otherwise - and declare I was attacking your view or supporting Grassley’s actions, specifically - is, unfortunately, missing the point. Again, though, thanks for writing in.
Regards
ed
Atlex
I support Thornton’s point. (Full disclosure–I am biased because I know many people with cancer and I also work in the pharma industry.)
Grassley is a critic of the pharma industry. (Full disclosure–Grassley wants to get re-elected and knows that being a gadfly to the pharma industry helps a populist candidate.)
Journalists love to go after the pharma industry (and other industries). (Full disclosure–Railing against big pharma sells newspapers.)
LVS despises the use of CNS medications in children. (Full disclosure–she has personally experienced a tragedy associated with the use CNS medications).
My point isn’t that Thornton, Grassley, journalists, or LVS are right or wrong, but that everyone has biases and not all biases are financially related (though they are the easiest to measure). Why are financially-related conflicts the only ones focused on?
Atlex
Ed Silverman
Hi Atlex,
Thanks for the observations, all of which are probably correct in varying degrees. My full disclosure - I’m not selling newspapers. (At the moment, we’re not selling ads on this site, either).
Yes, everyone has some form of a bias, because we’re human. Why are the financially-related conflicts getting attention? Perhaps those are the easiest to ascertain or, in some cases, point to in black and white. There may well be others in play, as you note. Each situation is potentially different.
I agree that the notion that a potential conflict doesn’t begin or end with someone who is in pharma or connected to pharma, a discussion we’ve had before. Conflicts come in all shapes and sizes, and I do my best to keep track of what may be pertinent in all situations. I’ve taken note of such episodes on the site in the past, sometimes with help of readers, as you know. And I’ll continue to do so when I believe they may be pertinent.
Thanks for the note,
ed
Nathan
Ed says:
“more disclosure is better than less - and that should apply to all discussions”
I disagree. The application of sound logic and accuracy of the facts are far more important than disclosure. In my opinion, it’s your job (as the journalist) to determine if the disclosure (or lack thereof) is relevant to the logic and facts. If it isn’t, then it isn’t worth bringing up.
“I deliberately didn’t suggest his view was tainted.”
Again, I disagree. Look at the title of your article. Instead of focusing on the important issue at hand, your title clearly indicates that you are more interested in the omision of Thornton’s employer than you are in the policy being discussed. That’s shameful in my opinion.
condor
Odd. Just. . . . odd.
How did this [orginal] story get so oddly conflated?
Someone appears on the pages of the WSJ, complaining about one Senator exercising the constitutionally-mandated duty of oversight [over an FDA-approval process, in this case], on our [the citizenry's] behalf, but does NOT disclose that he has “skin in the game” — a commercial, as opposed to personal, interest — and Pharmalot is, in some ill-defined manner, “aligned with the forces of darkness” for mentioning the commercially-vested-interest?! I. guess. I. just. don’t. get. it.
BTW, I also think “the lady doth protest too greatly” about outcomes studies being the death-knell of new drug development in cancer research. And that should be the real focus of commentary, IMO. But it is not the topic at hand.
It should be, though.
P e a c e
Nathan
Ed,
Let me ask you a hypothetical question: If Mr. Thornton HAD indicated his affiliation with GenVec, would you have written this article?
A basic premise of written language is that the opening and closing statements are the most important parts of an article. Your opening statement (the title) and the closing three sentences are focused on lack of disclosure. That strongly suggests to me that wouldn’t have bothered to cover this issue had the appropriate disclosures been made. Again, that’s shameful. Mr. Thornton brings up important issues that are worth discussing based on their merit (or lack thereof). Instead we’ve all wasted our time piddling over Mr. Thornton’s employment status.
CMC guy
Ed the headline on this piece, which I assume you wrote, detracts from the issue (as Nathan also suggests) and gives the impression of prejudice especially since the connection only comes out in your final paragraph of “investigative reporting”. IMO this headline abstraction is a regular occurrence that I typically write off to Journalism 101 learning to capture the audience’s attention which now-a-days tends to demand “sensationalism” and I look past it.
Further indicating “messages were not returned” can be misleading and interpreted as you “being ignored”. Perhaps Dr. Thornton could have added “these are an expression of my personal views” in order to capture where he was coming from but not providing a related business connection does not automatically invalidate what he has expressed.
I do favor more rather than less disclosure because it is helpful to understand motivations however I do not see hidden agenda behind everything (except in politics perhaps). Unless tag everything with all available info, which is impractical, there are going to be gaps. You felt a duty to fill a gap by your standards however others are acting in the way they see it.
Thom is correct about what Grassley is calling for in statement (FDA follow-up) although article above states “At issue is whether the FDA should use surrogate endpoints as the basis for approval.” I recall that was the suggestion when first came out and my reaction was as now that would hurt drug development. Maybe the foundations of the op ed are not totally there because reminding the FDA to follow their on rules is justified but a GAO investigation sounds like a hammer approach (again reflecting distrust for politicos).
Roy M. Poses MD
Maybe Mr Thornton should also have disclosed that the Sarcoma Foundation of America is funded in part by pharmaceutical and biotechnology companies. Its sponsors page (http://www.curesarcoma.org/sponsors.htm) lists Pfizer, Ariad, Ziopharm, Bristol Myers Squibb, Ortho Biotech, and Novartis.
Paul
Congratulations Dr. Thornton.
His article was spot on and he has explained why did not choose to disclose. I buy his explanation and feel comfortable.
CMC guy
condor please fly lower as I can not comprehend most of what you say. You took the tangent and did not focus on the issue so complaining about others following that thread is ridiculous. If you think Thornton is wrong and Grassley right then say so clearly and don’t obscure your message with prose (?not sure what to call it).
Thornton’s assessment is accurate as cancer (and most other) trials are so complex and if have only “gold standard” survival benefit target then will need to be bigger/longer and costlier (plus often more restrictive in patient inclusion). Approval on surrogate end points are not ideal clinically in most cases, however trusting they are scientifically reasonable offers opportunities to shorten cycles so products become available (with hope that the science rationale does lead to good clinical result long term). The conclusion that impact of Grassley could hamper/destroy development also is highly reasonable given that even now it is difficult to get companies to chase small and complicated diseases unless the numbers work out very favorably which is sad affair for patients and industry (block buster mindset another tangent that I feel contributes to lack of innovation). There could be consequences in pushing FDA even further down rigid dogmatic pathways that(IMO) are already misaligned at times.
condor
Hey, CMC Guy –
First, I apologize for being opaque. Let me be direct, this time:
I think one of our central differences will turn out to be that you seem to have a bias toward trying new compounds — I have a bias toward an old bon mot — “First, do no [more] harm.” I doubt we’ll get much, of any lasting intellectual benefit, past this point.
I will say that I, too do want innovation — and I, too do believe we should always move the science forward. I just don’t believe the straw man argument that pharma will fold up if it is not granted speedy approvals. I don’t think the two are mutually-exclusive.
I also do not buy the notion that getting every new compound into the oncology ward of every hospital is always a good idea — it will make more money for pharma, that is certain, but it may not improve outcomes, or improve lives, to any significant degree.
“First, do no [more] harm.”
I hope I have been plain enough, this time.
P e a c e
Nathan
Condor says: “First, do no [more] harm.”
You try explaining that one to the 45 year old father with pancreatic cancer with only two months left to live. Let’s get this strait once and for all: The CANCER is doing the harm — not the molecules.
HorusCat
Nathan,
I’m with you. We’re not talking about new allergy treatments or even mental illness. When your terminus is imminent, you may see the failure to offer experimental options as doing harm.
Ed Silverman
Hi Nathan,
A very belated reply since I actually took most of the day off ( I did work from 6 to 9 am ). To address your points - yes, I was emphasizing the omission of Thornton’s job, not the policy issue raised. That was the reason for my post, which explains my choice of headlines. That wasn’t clear from reading my earlier comments?
And I decided the disclosure issue, indeed, is relevant to discussion of the policy - NOT the policy itself - simply because a key affiliation wasn’t disclosed. Those are two very different things, but you continue to miss that point.
I’ve already explained my thoughts on this in my previous comments. But once again, full and appropriate disclosure provides everyone involved with a better understanding of how people come to the views being expressed. I don’t understand why you find that ’shameful.’ To my way of thinking, it’s necessary.
And no, I wouldn’t have bothered to write what I did if Thornton had provided the appropriate disclosure. Again, I didn’t address the underlying issue about surrogate endpoints or Grassley’s desire to see FDA follow-up. Nor did I suggest his views were incorrect because he failed to provide the disclosure. But the failure to do so detracts from the discussion of the central issue because it raises questions about his motivations.
And finally, I have covered the Avastin approval and the debate over the FDA’s decision on the use of surrogate endpoints in a couple of earlier posts. So before accusing me of being ’shameful’ for not covering that issue - a separate issue - please do a search on the site.
I do agree on one thing - the time for ‘piddling’ has come to an end.
Cheers
ed
Nathan
Ed, I feel that I’m beating a dead horse here — but if the issue was the disclosure, why go through so much trouble explaining the whole situation? The letter that Thornton wrote IS an important issue. I’m glad you brought it to our attention - so in that respect I’m glad that Thornton didn’t give his affiliation.
By the way, as I’m sure you are aware, I don’t find it “shameful” to want full disclosure. (though I don’t really find it an especially important topic) Rather, I find it shameful that such an important topic (surrogate endpoints in cancer research) was glossed over and instead the focus became disclosure issues.
zzz
Mark Thornton is a director of DrugWonks, enough said, sick joke over.
Go here:
http://www.sourcewatch.org/index.php?title=Center_for_Medicine_in_the_Public_Interest
scroll down to Board of Directors (of CMPI / drugwonks)
CMC guy
condor you are still fuzzy. My so called bias is more pride in what I selected to do as chemist and what I believe pharma can do to help treat people and that we still have a long way to go in many areas (cancer most definitely). Effort to develop new drugs is not necessarily mutually exclusive of do no harm and in fact would say that indeed a desired primary goal. Unfortunately it often does not work out cleanly as desired and in attempt to help side effects are encountered. Science is often messy and progress slow particularly when you do not fully understand systems that are dealing with. If there was a way to get to safe and efficacious medicines without risk we would practice that route.
Its not straw man that targets and treatments will not be pursued by pharma unless they see viable ROI and approval process requirements directly impacts the calculations. You attempt a straw man stance when suggest want every oncology drug in every hospital to increase pharma profit. No one said this as far as I know and again because we lack full predictive capabilities situation occurs where drugs get used widely. I trust committed doctors and informed patients are the ones ultimately managing this and that advancements result.
zzz
LOL,a DRUGWONKS director, a pharmaceutical funded site, is believed? JEEZ how gullible people can be when listening to pharma spin.
CMC guy
Nathan unfortunately conflicts of interest, real or imagined, is a hot button issue here and something some people can not seem to get past. My concern is that may be like “boy who cried wolf” story with all the fervent demands to disclose every minor thing diverting attention to real problems out there.
zzz
Seems some people cannot get past knowing the difference between a pharma funded creep and ethics.
zzz
Rather sad really. Ethics in science is so important, but so many people will stand up to defend those without ethics if and when it suits them. Too sad and pathetic for words.
Ed Silverman
Hi Nathan and CMC,
I took the trouble to provide as many explanations as I did simply because you and a few others objected to the fact that I raised the disclosure issue - and accused me of using that to obscure discussion of surrogate endpoints and follow-up studies. Again - those are two separate issues.
While I’m here, I’d like to point out that I don’t view my post as a diversion from the ‘real problems’ out there, because disclosure itself has been a real problem. And in this instance, Thornton’s failure to note his employer is not a ‘minor thing,’ because it’s central to shaping his view and interest in the topic. And that merits mention.
G’night folks
ed
condor
CMC Guy — One last shot at this, here:
For the truly terminal, near-death oncology patients, they are always able to sign informed consents to joine EXPERIMENTAL treatment studies — read not FDA approved — if they go to the right teaching hospital. We agree on this much — that option should always be, and will always be, available to the truly desperate, end of life patient.
Contrast that with my “available in every oncology ward” statement.
ROI must be measured fairly — often Big Pharma stacks the deck on this calculation, suggesting that it will only have a few years of exclusivity — when, in actuality, we have seen over and over again — through patent extensions (at the USPO), combination-therapy filings (at the FDA), and partnerships with other companies — the period of “effective” exclusivity regularly lasts for decades.
And that truly amps the ACTUAL ROI, as opposed to the “projected” one declared when the filings are first made. It is an art more than a science, IMO.
Now, I want to be sure I am understood: I think Ed’s story on non-disclosure was very fair, very accurate and solid investigative journalism — right down the middle of the fairway — it just doesn’t sit well with many of those here assembled because, frankly — you all are too accustomed to reading MSM reports — often authored by simple STENOGRAPHERS — cut and pasted from Pharma press releases.
It is well-past time for some independent sunshine. And Ed is offering it. If you don’t like it, slather on your Coppertone 45 and/or stay indoors. But the sunshine will not go away — we are looking at “a Democratic landslide this Fall of 2008″ — just ask Rupert Murdoch. So buckle up.
Just my opinion — but it should be yours, too.
Nathan
Condor says:
“the period of “effective” exclusivity regularly lasts for decades.”
That is bull****. The USPTO grants a short (1 year) extension in exchange for doing pediatric studies. There are no other extensions. Formulations are subject to extend the “effective” patent life, but only when the new formulation is truely effective. A generic company is free to sell the old formulation as soon as the composition of matter patent expires. After the preclinical and 3+ clinical trials are done, there is typically about 8 years of patent life remaining. Getting rid of surrogate endpoints shrinks that to about 5 years. Cancer research is barely cost-effective currently. Why do you think cancer drugs are so expensive? They would probably double in price if surrogate endpoints were eliminated.
Now, if patent life were extended (25-30 years instead of 20) or if drugs were givin a “minimum period of exclusivity” following FDA approval, then I would support getting rid of surrogate endpoints for cancer research. I agree that better drugs would result. However, doing so would nearly eliminate the profit motivation for cancer research.
Condor says: “I think Ed’s story on non-disclosure was very fair, very accurate and solid investigative journalism”
Ed’s reporting is fine. It’s his choice of topics that bothers me. Fine, Thornton should have given his affiation. So what? Does Ed disagree with Thornton’s findings or his conclusions? Did Thornton lie about or twist evidence to support his view? THOSE are the important questions. This was an editorial. Either he has a valid viewpoint or he doesn’t. His line of work, the number of kids he has, the amount of mortgage, his race and marital status are really not relevant. Either he has a valid arguement or he doesn’t.
condor
“. . .Formulations are subject to extend the “effective” patent life, but only when the new formulation is TRULY EFFECTIVE. . . .” [Emphasis supplied; typo corrected.]
Define “IRONY”: see above.
Nathan — we are simply going to disagree about this — and disagree wildly. Let’s talk about exclusivity *in practice*, on actual drugs, not *in theory*, by statute or by rule. The examples are legion — even in Oncology.
It is unbecoming (on your part) to suggest that cancer-field compounds are barely profitable “as it is.”
This would take a lot of my precious time, but I may choose to highlight some of Schering-Plough’s specific compounds — to make the specific point, in a general way — on my blog, at length — but as a long-time high-stakes financier, recovering-lawyer, part-time scientist, reformed-accountant and analyst, and now long-time medical-sector executive, I can tell you — show you, even! — just how *profitable* cancer already is.
But we’ll need to pick a specific example. That way, I can show you just how long the tail of revenue really is. [Generics don't end a drug's life; they simply decrease its cash-flow -- and the decreased level of cash-flow often runs on, and on, into multiple decades. . . .] There is also the issue of how many [often tenuous, usually non-cash] extra-costs and expenses are piled onto the model’s front-end, to make the drug *appear* less (shockingly) profitable.
But maybe, we should just call it a day (I’ll save my time; and you’ll be able to still cling to your Pharma-talking-points, here) — if you believe that Pharma does cancer research out of the goodness of their collective hearts — we are simply too far apart, to have any meaningful dialogue.
Cheers!
condor
Ack! — once again, I went on too long — I must learn from Ed, here — The first sentence of mine, quoting Nathan’s — sets out my whole concern about the tenor of this thread.
Nathan said about TEN times as much as he meant to, there.
Cheers!
scarletrat
Aside from the issue or non-issue of disclosures, it shouldn’t detract from the message communicated in the editorial–a necessary one. Grassley’s micromanaging and second-guessing of the FDA has had and will continue to have determental consequences. I wonder what his qualifications are to understand the validity of PFS as a meaningful surrogate endpoint. We have to strike proper balance of benefit risk and part of that is access to medicines, especially as we move to personalized medicine. I think some of what Grassley has stated in past and criticism of FDA has been warrented but to attack product decisions–based on science–is at best disingenous and at worst can cost lives.
Dirk Haussecker
I agree that Big Pharma has to fault itself for the political assault it is facing now due to many mistakes that have affected both patient safety and the sustainability of medical care. This was often facilitated by financial ties to doctors and other opinion makers. However, the time has come that the obsession about conflict-of-interest has marginalized those that are qualififed to decide on important medical matters. This includes the FDA, and it is ironic that they now claim a lack of qualified manpower to explain their delays in approving much needed drugs.
When I read Dr. Thornton’s impassioned and bold plea against Mr. Grassley’s efforts to deny terminally ill cancer patients timely access to promising drugs that have shown little side-effects in clinical trials, I never doubted the sincerity of his intentions, and I am not surprised at all to find out that he had been personally touched by cancer. Although I do not want to spread bad karma, I cannot help but wonder whether a similar case in Mr. Grassley’s family would make him change his populist mind.
Disclosure: I am a scientist in academia who is an advocate for RNAi-based drug development and who would benefit from a less hostile and conservative drug development policy.
CMC guy
Nathan I see a key part of my last message got cut off - my condolences/prayers offered for your father- that is the problem I meant knowing not “good” options out there.
condor I’ll try again too as the major difference in the points on ROI is I am talking about front end project evaluation and your comments deal with the back end (so I do not consider the unknown “effective” value since it is not part of R&D decision process I have seen). If you don’t think it effects R&D/drugs targets and Grassley approach would not have negative impact then you are incorrect (and this was the context of my comments) because yes as a business pharma must make money so are not going to spend on something that they do not calculate will be profitable.
I do not deny your back end analysis can be correct in some/many cases and can be means to extend ROI lifecycle management of drug as common practice of pharma (and other businesses). Again that is not as direct influence to early stage although trust that profit gets cycled back to support new projects. Cancer compounds typically are low return, sometimes due to small patient populations, so it takes a long time to reach positive (whether you wish to believe are not) although once they do can provide steady income for a company. Generic companies do not go after low margin products and thus cut into successful drugs.
Nathan
CMC guy - sorry for the confusion. My father doesn’t have cancer, just using that 45 year old father as an example to remind Condor that the real enemy is cancer – not drugs.
Condor,
One thing to keep in mind about return-on-investment of cancer drugs (and other drugs too): If you look at individual drugs, I agree they are sometimes very profitable. But remember, each successful drug has to pay for the development cost of ALL THE FAILURES along the way. (of which there are MANY) Some niche products we market don’t even make enough to cover their own development costs, much less the development costs of the two dozen failed projects that never made a penny.
Nathan
Woops, I forgot. Per the new “unofficial” policy that Ed has instigated on this web site, I’ll start including this full disclosure at the end of each of my posts: “I work for a pharmaceutical company with an income of approximately $100k per year. I have roughly $10,000 in company stock. I have approximately $65k in my 401k, of which ~10% is invested in the healthcare industry and an unknown percentage in pharmaceutical stock. My grandmother died from cancer and my grandfather from Alzheimer’s. My father-in-law is a colon cancer survivor. I have two young children and I wish them to grow up in a world with better treatments for diseases than we currently have. “
Bob Freeman
Nathan, I disagree with one of your points: pharma prices do not recapture R & D costs. Those are “sunk” or dead weight costs that expensed in the year in which they occured. Once spent, they are not recoverable. It is true that drug prices have to cover ongoing costs but there is a disconnect between costs and prices; viz., prices are set “close” to that of competiting therapies. In the absence of competing products, the manufacturer will set monopoly prices until new compounds enter the market. But, the bottom line that high prices are necessary to recover R & D costs is a myth. I wish PhRMA and its member companies would stop repeating it.
It is also true that the intitial price of an oncolytic will be in line for the specific type of cancer for which NDA approval was given. This creates a challenge since subsequent approvals may be for cancers for which the pricing structure is entirely different (lower). And, if a company recognizes that the bulk of the prescribing for off-lable useage, pricing will often refect that reality.
Novel therapies with relatively high prices to the existing therapy will often show lagged adoption because there is no economic incentive for the oncologists to shift away from the existing cocktails, since reimbursement is known and stable. The last thing oncologists want is reimbursement hassles.
I agree with Condor entirely on the long effective patent lives of oncolytics. I would also argue they are highly profitable because of low marketing and sales costs and a unique distribution channel, quite unlike those of other Rx goods.
HorusCat
Bob,
I think your point about R&D costs being “sunk” and therefore not recoverable and unrelated to the subsequent pricing of the drug is misleading. The cost of developing a drug may be accounted for in a way that makes the expenses unrecoverable according to accounting principles, but the companies are making pricing decisions meant to provide revenue streams for FUTURE development costs of other drugs. If it costs $1 billion to develop new drug Z, then the company at some time in the past made pricing decisions on other, antecedant products meant to provide future revenue to develop that drug Z. The money has to come from somewhere–and as far as I can see, the primary source of revenue for pharma companies is the sale of pharmaceuticals. Furthermore, the sale price of a drug not only includes the goal of providing revenue for further drug development, but also the goal of providing sales and marketing revenue for the drug itself.
Your point about sunk costs, etc., is accounting legalese.
Bob Freeman
HorusCat, If we were using cost-plus as the way to set pricing your argument would be more solid, but we don’t. In spite of all the analytics used in market research, pricing comes down to market competition and the ability to segment customer segments by price. We also segments markets on a geographic basis, largedly driven by their willingness to pay. I will agree that prices have a forward-looking component much like retail gas prices have and the forward-looking component is R & D cost driven. I believe all of the off-shoring and out-sourcing the industry is doing is to reduce its cost base permantently.
I am intimately familiar with long-range financial planning in the industry and each marketed product has buildt-in price increases throughout its projected life cycle. These are always subject to change and R & D spend is one of those drivers that can change life cycle planning assumptions.
As far as accounting-speak is concerned, our failure to amoritize R & D costs leads to revenue streams that are not off-set by cost streams and, as a result, overstate profits and cause ongoing grief.
HorusCat
Bob,
I bow to your superior accounting knowledge, but note that R&D costs are still figured in. Pricing between competitors is not always within a narrow range–note the differences in the atypical antipsychotics–a $250 spread is not trivial. Of course, we must acknowledge that what is published as the “cost” of a drug is not what is paid by the insurance companies or the government. Rebates, bundling, etc make the true price of a drug very different from what the press may say it is.
In addition, I must say I find nothing wrong with building in a healthy profit, as well. That is the nature of capitalism, and I don’t believe pharmaceuticals should be any different. The profit margin of pharma is not much different from that of other major industries. Only the never-challenged assumption that medicine must be provided for all by the public treasury or private insurance leads one to conclude that pharmaceuticals (or medicine in general) must be an altruistic endeavor wherein no one enriches themselves.
Bob Freeman
HorusCat, you’ve hit on one of the key issues in pricing: transaction prices are trade secrets and the difference between “list” prices and those actually paid are often huge.
to your other point, the R & D infracture remains and in that sense, its costs have to be covered by prices in order for research to be sustained. Free cash flow and operating profits are essential. I don’t have any problem with the profit margins pharma earns–it has to be put in context with the type of industry we are.
By the way, I can relate to your situation from a few weeks ago resulting from donating blood. I had an emergency root canal last week followed by signficiant swelling and pain. It has taken forever to get back on my feet.
Ed Silverman
Hi Nathan,
I enjoy sarcasm, but just for the record - no, there’s no unofficial policy about disclosure. But feel free to disclose as much as you like. Maybe it will get others to think harder about the issue and they’ll recognize its in everyone’s interest to have an understanding of what motivates or influences people who are involved - or trying to get involved - in decisions that affect them.
Cheers
ed
Bingo
Nathan,
Although this is somewhat off topic, your statements about patents are just plain wrong and shouldn’t go unchallenged.
“The USPTO grants a short (1 year) extension in exchange for doing pediatric studies. There are no other extensions.”
35 USC 156 provides for a patent term extension to compensate for delays in FDA regulatory review of a new drug application. You can easily look up which products have received extensions on the USPTO website.
http://www.uspto.gov/web/offices/pac/dapp/opla/term/156.html
“A generic company is free to sell the old formulation as soon as the composition of matter patent expires.”
Where did you get this idea? This is flat out misinformation and is not even close to the truth.
The composition of matter patent is the most difficult patent to get around, but other patents are still relevant and often delay or exclude generic entry to the market. If the formulation is patent protected, a generic must develop a non-infringing but bioequivalent version and risk extended litigation and damages if it is found to have infringed a valid and enforceable patent.
truthman30
Pharma always uses the claim, that any criticism of its practices will result in “catastrophic effect on America’s ability to develop new drugs”
This is complete and utter bullshit..
If pharma was to spend the same ammount of money it uses for marketing on proper research , proper trials and proper drug development we would have better , more effective drugs on the market…
Instead we have a situation where pharma spends considerably less on R and D than it does on advertising…
This results in crap quality, defective compounds and damage to patients..
These drugs are rushed to market in order to make a quick buck..
They are not adequately tested or trialed because pharma keeps the bulk of its money for marketing its drugs…
It is ironic really because if a drug was of good quality and did what it was supposed to do, then it would be a success anyway and pharma wouldn’t need to have these billion dollar advertising campaigns…
The reason why pharma drugs have reached such bad quality is because pharma does not invest in proper research and clinical trials so it has to market the drug regardless of adequate efficacy…
Doc
Sad but there are no real surprises in this story, pharma as usual holds itself above all reproach and acts as if the world depends on it for survival. Good products need little promotional dollars and effort behind them to actually benefit mankind - put the bucks into R&D.
condor
Sen. Chuck Grassley responds — directly — here:
http://shearlingsplowed.blogspot.com/2008/06/senator-grassleys-response-to-last.html
[Looks like Ed just ran it, too, as a new post.
Check the top of his Pharmalot page.]
pg
What an EXCELLENT response. A good man.
Nathan
Bob,
I lost track of this conversation for a couple days. Anyway, I’m not familiar with pricing strategies for oncology drugs. I am, however, very familiar with how how much money pharma reserachers spend — A LOT. Our revenue comes from drugs. Most drugs fail. Those that succeed provide ALL the revinue to cover the cost of the currently failing projects. There is no way around it. No one else picks up the tab for failed projects. I comes strait out of our bottom line. Very simple — it doesn’t take any fancy economic terms to understand it.
Nathan
Sorry Ed, I forgot my disclosure again. My above post was only slightly sarcastic. It seems to have become the mantra of your site that you don’t believe logic, facts, and reason. Instead, you believe in full disclosure. So, once again, here’s my disclosure: “I work for a pharmaceutical company with an income of approximately $100k per year. I have roughly $10,000 in company stock. I have approximately $65k in my 401k, of which ~10% is invested in the healthcare industry and an unknown percentage in pharmaceutical stock. My grandmother died from cancer and my grandfather from Alzheimer’s. My father-in-law is a colon cancer survivor. I have two young children and I wish them to grow up in a world with better treatments for diseases than we currently have. “
Ed Silverman
Hi Nathan,
The sarcasm isn’t necessary and I take responsibility for my posts. However, the comments are from you and many others - in and out of pharma. There is no ‘mantra’ here - otherwise the discussion would stop because everyone would agree with one another. I think you’re getting unnecessarily personal, as well, by saying I don’t believe in logic, facts and reason. How so? Because I believe disclosure is a topic worth discussing?
Once again, disclosure is, itself, a separate issue from whatever topic may be discussed in an editorial or another forum. I didn’t invent the notion, by the way. There are people who believe it’s in everyone’s interest to have an understanding of what motivates or influences others who are involved - or trying to get involved - in decisions that affect them. Step back and think about how that may apply to any number of situations in your own life.
Let’s stick to a genuine discussion of issues and dispense with the unnecessarily caustic personal remarks.
Regards
ed
truthman30
Thanks for the disclosure Nathan..
But I would have to disagree somewhat about your defence of the industry and its spendature on R and D…
We all know the pharmaceutical industry spends a lot on R and D, but it spends much more on the marketing and advertising of its drugs after R and D..
Drugs have become less about efficacy and effectiveness and more about brand and sales ..
This is unfortunate and until this scenraio is reversed we will continue to have drugs like Vioxx, Paxil, Avandia and Chantix messing peoples lives up ..
If a drug is safe and effective it will always sell no matter how much or little is spent on marketing it..
And it seems to me that pharma should invest more in better clinical deelopment and longer trials instead of rushing these drugs to market and decieving the consumer about efficacy..
Why not make good drugs with good efficacy?
That’s something which should be in everybodys interest..
Caterina
If you look at today’s PharmaLive feed, Grassley has a statement in which he makes several of Ed’s points. If you’re going to publish an editorial badmouthing a senator (and mistating his position, to boot), you owe it to your readers to publish the affiliation(s) and potential conflicts of the author.
Nathan
Ed,
The sarcasm is perfectly necessary. You criticize people whenever they don’t provide adequate disclosure. (generally people affiliated with the pharma industry) That’s fine. But I want you to establish some clear guidelines for when disclosure is necessary and when it isn’t. Also, you need to establish guidelines for what constitutes disclosure. Financial ties only? Previously it appeared that you had only “required” full disclosure for peer-reviewed journal articles. Now, suddenly, you want it from people writing an editorial to a newspaper. Next are you going to want it from people posting on your site? Half of the vocal pharma critics on this site run are ex-SSRI drug users and run anti-pharma blogs of their own. They generally don’t disclose that information unless you ask them point-blank. I think it is very relevant - and it should be disclosed. We should demand full disclosure from EVERYONE. I think you are being completely arbitrary in how you are handling this disclosure issue.
Ed Silverman
Hi Nathan,
I wasn’t sarcastic with you, so please try to refrain from doing so now and let’s have a useful discussion.
To answer your request, I don’t have a firm guideline on disclosure in the comments, because I don’t believe it’s my job to monitor the conversations here to such a level. I’m generally concerned with the content of the posts. Although I agree that it would be helpful to encourage more disclosure, given the environment.
So if people want to disclose, that’s fine. If others want to look for vested interests among the other commentators here, that’s fine, too. Have at it. But if you want to hold me responsible for disclosing the vested interests of the vast number of people who stop by and share a thought, well, I’m afraid that’s just not possible.
As to my posts, I try to note conflicts when I find them and believe them to be pertinent, whether it’s a clinical study, an FDA advisory committee, an advocacy group, public broadcasting program or a newspaper editorial. There have been examples of these other instances, by the way, not just clinical studies, as you suggest. In particular, these two recent posts involved newspaper editorials…
http://www.pharmalot.com/2008/05/a-conflicted-campaign-to-attack-industry-criticism/
http://www.pharmalot.com/2008/04/massachusetts-docs-to-lawmakers-no-gift-ban/
Perhaps you missed these, but I’ve been consistent in trying to point out conflicts, disclosed or not, simply so my readers/viewers are more aware of the varying interests that may influence people whose actions may affect them. And that works both ways, such as the JAMA study about Vioxx ghostwriting that was authored by individuals who have served as expert witnesses for plaintiffs’ lawyers, or studies by psychologists who question the utility of certain meds.
I don’t know why you’re so angry at me over this issue, but I’ve tried to be clear and consistent, and I’m not applying any smell test or litmus that other journalists wouldn’t use. This issue isn’t new or rocket science. It’s about peeling back curtains so the best possible deliberations can take place. But such progress can be impeded when interests are hidden.
Time for me to move on to something else this evening,
ed
CMC guy
Busy day so didn’t comment earlier: Nathan I’ll chime back in and say I think you do seem to have gone a little far here. As with every issue there are multiple facets and are points when views collide and may not be moveable. Continue harping and being dismissive of other perspectives is not going to add much to discussions, which is what this forum provides. I still think some of the conflict of interest/disclosure advocates on this blog have taken it to anti-pharma/FDA extremes, which was part of my impetus, but do not direct that at Ed who established his position and has indicated reasons clearly. You may disagree with Ed but I suspect personal attacks and rants are counterproductive to most readers. Move on to issues that you consider are more important.
Based on face value of Grassley comments in latest release this whole subject is clouded in perhaps misconceptions or over interpretation of statements. A key statement is the series of articles “At issue is whether the FDA should use surrogate endpoints as the basis for approval” seems clear in isolation however was never direct words from Grassley that I can tell. Likewise, Ed’s title and disclosure comment, was taken as a distraction (by myself at least) to that critical (if miss-founded) proposed change in approval process even though I did not believe it was intended that way. I retain that core view about the approval issue but do apologize (to anyone who took offensive) if I was over aggressive in defending that.
Chilly Willy
Unless the US develops a more European approach to R&D, the US pharma industry will be eating up over 90% of our country’s GDP in 20 to 30 years. That doesn’t leave much for anything else. Especially with decisionmaking boneheads thinking that throwing $300 million extra of our budget for FDA “enhancements” will do any bit of good whatsoever.
Bob Freeman
Chilly Willy, as long as the US public considers death an option and the pharma cartel continues to design public programs (Medicare Part D) that benefit them, R & D won’t really change. Plenty of life-style drugs with heavy consumer demand and willingness to pay (or more accurately, have someone pay in their behalf).
Dan
My question as an ignorant layperson is, how does the FDA determine which gets approved and which does not. It appears that there is no objective protocol.
Bob Freeman
Dan, if you’re asking about marketing approval for safety and efficacy, 2 independent Phase III randomized clinical trials are required and the results have to be consistent. (An exception exists that allows one, large mutli-national, multi-year trial to be split into a US trial and an ex-US arm is sometimes allowed.)
The FDA, though, is not a monolithic agency. It’s organized along therapeutic areas and the standards vary (hard versus surrogate endpoints; placeo-controlled trial vs. active control group) among the groups.
But generally, you have to have 2 well-controlled trials and a favorable risk-to-benefit ratio. If serious adverse events appeared in the trial, approval may be contingent on the company performing post-marketing safety studies. (Another issue since compliance with this requirement has been spotty.)
CMC guy
Bob you provide a good overview and perspective on FDA but do not mention (directly at least) the heavy (pre-defined) statistical requirements associated with approval. In theory stats should provide an “objective” basis for approval, in practice still can be complex interpretations involved. The biostatistics greatly influences the clinical trials (design and execution) and whether surrogate endpoints may offer quicker route to demonstrate potential value of the drug (as per initial post here that again should also be subject to post-approval study/verification).
Bob Freeman
Excellent point, CMC guy. The question was somewhat open-ended so I didn’t go into any depth at all. Thanks for adding this.