Wednesday, September 2, 2009

Chemotherapy Efficacy?

A great NY times piece from yesterday on the movement of the pharmaceutical industry into novel cancer therapies. With patents due to expire on big moneymakers like Lipitor and Norvasc, the industry has refocused its emphasis on new oncologic drugs (860 drugs now being tested in clinical trials). The reason is all too predictable--- you can make a lot of money selling cancer drugs. Since 2006, cancer-related drugs have been the biggest selling category in the industry. Tarceva (a pancreatic cancer drug) and Erbitux (for metastatic colorectal cancer) both cost thousands of dollars per month, sometimes over $50,000 for a treatment cycle. Drugs coming down from the pipeline are sure to be just as pricey. Assuredly these pharm companies have invested millions of dollars in the research and development of the new therapies. From a strict dollars and cents perspective, I'm going to give them the benefit of the doubt to the extent that the exorbitant costs of these new drugs is at least partially justified.

The controversy arises when we start to examine the effectiveness of these newer medicines. For example, the metastatic colorectal cancer drug Erbitux certainly represents an innovative breakthrough in the war on cancer--- use of a monoclonal antibody that specifically targets the Epidermal Growth Factor Receptor, thereby slowing the progression of the disease--- but unfortunately it only adds about about 6 weeks to a patient's life when compared to placebo. Tarceva, the pancreatic cancer drug which targets a specific enzyme on the EGFR protein, improves survival by a mere 12 days compared to those who do nothing at all. At a cost of $3500/month.

Now that's just astounding. And I find it a little unsettling as well. The insidious inference is that these drugs are being offered to people who are vulnerable and bereft of hope. The oncologist tells them they have an incurable disease but this carrot is dangled before them. Try this fancy new drug. We can't guarantee it will prolong your survival or make your life better. But it may. And the flicker of light that such a conversation can elicit gives birth to a billion dollar industry. This exploitation of the dying is reason enough to look harder into the motivations and efforts that go into the creation of these new therapies.

The other reason is that it brings us full circle back to this concept of "Comparative Effectiveness". What the hell does this actually mean? How are we going to define it? Effectiveness has to mean much more than "treatment A leads to better outcomes than treatment B" irrespective of costs, side effects, and the degree to which it is more effective. From the Times article:
“As long as the marketplace does not distinguish between modestly effective drugs and dramatically effective drugs, there won’t be an incentive to shift resources to a greater emphasis on a larger benefit,” said Dr. Neal J. Meropol, an oncologist at the Fox Chase Cancer Center in Philadelphia who has been studying drug prices.

Ezra Klein has a surprisingly weak take on this issue in the WaPo. His stance is that the federal government should just use its muscle to bargain down the prices of these newer therapies, being careful not to compromise the innovation benefits that patients receive from them. Which of course is a convoluted, incoherent argument. Moreover it simply avoids the entire point of asking whether or not it is worthwhile for the pharm industry to invest so much time and money into the development of marginally effective cancer treatments.


Dana said...

Does every pancreatic cancer patient gain 12 days on Tarceva, or is it one in thirty who gains a year? I guess when you are dealing with nameless, faceless statistics neither seems to justify a cost of $3500 per month. But if one were in Randy Pausch's shoes, that 1 in thirty chance to have another year to spend with wife and children would not make it such a simple choice. That's why this whole debate is so difficult, and why I don't want to have some committee just using statistics to deny availability to a particular treatment.

Also, Dr. Meropol's quote doesn't hold water - drug companies are not satisfied with incremental improvements – their goal in their development of new drugs has to always be to hit it out of the park because that’s where the real money is – incremental improvements are simply the byproduct and not the goal of their research. Why not let them market them fairly and honestly, and if physicians and patients choose to use them, it will fund their continued research to find the ultimate cure.

Jeffrey Parks MD FACS said...

I'm usually aggressive when it comes to providing maximal treatment, as long as my patients are informed and realistic. But a 12 day benefit for a drug that costs tens of thousands of dollars is pretty borderline. If only 1/30 are benefitting, I tend to side with the argument that it isn't the medicine, but rather the biologic nature of the tumor that extends an individual's life. Unfortunately, statistics are necessary. Cold hard numbers are the only objective way to fairly allocate our limited resources. There certainly needs to be some flexibility and individualization to any allocation system, but that needs to be balanced by some depersonalized objectivity.

And I believe you're being naive in thinking that drug companies define a "home run" by the drug's relative efficacy. A home run per a private enterprise, capital driven entity like a pharm conglomerate is one that makes a boatload of cash. If we lower the bar on how we define efficacy (survival benefits of days or weeks) then we do a disservice to individual patients and society both.

But this is the conversation we need to be having on a national level; measured, open-minded, and rational. These isn't about death panels or rationing boards. We can disagree and still be reasonable....

Anonymous said...

Where are the pics of the Parks clan?

radinc said...



I totally agree with your post btw.


Anonymous said...

Though I don't disagree with your conclusion (we need to have a rationale national debate). Remember, these new agents are targeted therapies that did not exist 10-20 years ago. The more we learn about the biology of cancer, the more targeted theapies will be used and hopefully the longer survial of the patient. If pharma (and more importantly university research labs) do not research and produce these compounds who will? Our local alties with their gobblygook? Yes you gave examples of relative low performers. However, tarceva for example has a real role in the non-smokers subset of adenocarcinoma. Also look at Rituxinmab and Imitinib. Real success stories for CD-20 positive lymphoma and CML/GIST tumors respectively. I think the bigger issue here is, why does pharma charge rates to support bloated advertising and sales? Why should there be DTC advertising for agents that you cannot get without a prescription (and in oncology rather specialized knowledge even at the MD level). What is the real need for these drug reps in today's era in which more and more hospitals, universities, MD practices are refusing to see them? The use of a drug should be based on the evidence and not the sales pitch. I will say from experience, I will not deny a medication even with limited efficacy, to a patient with relapsed/metastatic disease, the wish to continue aggressive treatment, and the performance status to do so. My duty is to the patient not to society.

Victor Lazaron said...

The problem is the confluence of three things:

1. The incredibly poor cost effectiveness of these drugs

2. The incredibly high cost of the drugs

3. The insulation of the patient from any consideration of cost

If I were Randy Pausch knowing what I know about tarceva AND I could choose to pay for it myself or not, I would not pay for it. I would save that very large amount of money for my son's future. Randy was a pretty smart and sensible guy and I bet he would do the same. The problem is there is absolutely no consideration of cost in any of the choices made. I don't have to spend my money on the tarceva - I can spend YOUR money on it (literally if I am on medicare or medicaid, through higher premiums if I have private insurance.) Why should I be able to do that. It is just as irresponsible to spend your money on a very expensive minimally effective therapy.

It seems to me there are three ways to handle this problem.

1. A panel empowered to make coverage choices on a cost-effectiveness basis - like NICE in Great Britain.

2. Very open, transparent choices in insurance. You can buy a basic policy which would not cover these therapies. You can buy supplemental policies covering the very expensive stuff. One could be a high-end cancer therapy policy. One could be for robotic surgery - don't buy it and get a more conventional procedure, etc. etc.

3. Just stop approving treatments like tarceva in the first place. Only have them available through trials.

I personally favor option 2, and if I were in charge of health care reform - the basic policy would be paid for by government and apply from cradle to grave. The ONLY role for private insurers would be in the supplemental insurance market, much like we have supplemental medicare policies today.

Of course I'm not in charge of anything...

Jeffrey Parks MD FACS said...

I like option #2 too Victor.

The disconnect between the cost of therapies and the people ordering/using them is the big problem here, as you say. Involving patients in the nuts and bolts of the finances of their policies would be beneficial for all.

Finally, just to reiterate: who is more likely to ration (or in private covergae vernacular, deny coverage) when dealing with these high cost/low efficacy therapies----the government or a for profit insurance conglomerate?

The Happy Hospitalist said...

Didn't you scold me last month for suggesting that it shouldnt be up to the patient to decide what the worth of 12 days is ( indirectly) if they aren't the ones paying for it?


Jeffrey Parks MD FACS said...

I don't think so Happy. First of all I don't scold; I prefer to "berate" or "castigate".

In all seriousness, I think you're trying to bridge two tenuously related issues here. This particular post aimed to draw attention to the disconnect between the efficacy of certain chemo drugs and the ridiculous cost of prescribing them. There is a drive from the pharm world to make these newer drugs more popular and more commonly used. But the "science" is manipulated to facilitate that. The word "efficacy", when defined as a mere 12 day survival benefit, is dangerously depleted of any substantial meaning. If I were counseling a lady with metastatic pancreatic CA, and she told me that her oncologist wanted to start Tarceva on her, I would make sure she was completely informed of what she was getting herself into. Agreeing to proceed with adjuvant palliative chemo on a 90 yr old lady with metastatic breast CA (using regimens which improve survival to a magnitude of months andeven years) after counseling her of all the options/risks/benefits is an entirely different matter. The point of this particular post was simply to illuminate the twisting of terminology (i.e. efficacy)that occurs for corporate financial benefit. The intimate doctor/patient relationship, an honest exchange of data and risks of chosen treatment strategies is a different animal.

Formulaic, algorithmic management of individual patients isn't going to win you many fans. But it's certainly reasonable to question the conclusions drawn by the profit driven pharm industry, given that this is the data we use to conduct the real business of medicine in our clinics....

The Happy Hospitalist said...

I get it. It's OK to deny chemo when it doesn't work well, or it may only work well for 1/30 people. It's OK to give chemo when we have no data it works in 90 year olds, but may increase survival by weeks, or it may not.

I understand you now.

Jeffrey Parks MD FACS said...

Nah, you still miss the issue. I not talking about "denial of care". I'm talking about using words (in this case "efficacy") in their proper context. Otherwise, the decision making process that occurs when a patient visits with a doctor in the office is compromised. We use the best evidence available. It's disigenuous to say that because there is no data on 90 year olds, then there is no science behind the decision to proceed with treatment. When would we ever get evidence? Randomized controlled trials on 90 year olds? In this case, it isn't unreasonable to extrapolate from the data that is available.

It's really pretty straightforward. The language we use to communicate with our patients needs to be dependable. If you're selling a patient on the "efficacy" of a potentially toxic experimental medicine that will maybe add a week to their survival, you've done a disservice to the profession. On the other hand if you can honestly say that the drug in question is not likely to confer statistically significant benefit, but may in rare cases extend survival, then you've entered into the realm of an "honest doctor/patient interaction". If the patient decides they want to proceed with aggressive therapy despite the odds, then so be it. Insurance may deny care. A government panel may deny care. It's out of my hands. But at least I know I've done my job as the patient's advocate and physician.

Anonymous said...

Do us all a favor. Look up the treatment options in metastatic breast cancer. I thought I know oncology when I was a hospitalist. It wasn't until I became a oncologist I realized that I didn't have a clue about treatments from an ONCOLOGIC standpoint, rather only from a internal medicine standpoint.

Anonymous said...

Anon 9:59,
Happy likes to play that game of "I know you are, but what am I ?" he's a real PITA that way. He can go on absolutely forever with it.