Wednesday, August 8, 2012

Kolodny Responds to UPDATES on PROP Petition

FeedbackAs discussed in recent Pain-Topics UPDATES [here] and [here], on July 25, 2012, Physicians for Responsible Opioid Prescribing, or PROP, submitted a Citizen Petition to the United States Food and Drug Administration (FDA) requesting labeling changes for all opioid analgesics when it comes to their prescription for noncancer pain. In fair balance, we extended to Andrew Kolodny, MD — president of PROP and a principal signer of the Petition — an invitation to submit for publication a rebuttal article commenting on our UPDATES and/or further presenting his group’s perspectives.

Dr. Kolodny promptly responded and we thank him for that. Following, is the text of an e-mail received from him this afternoon (8/8/2012, reprinted with permission), as well as the press release that he requested we reprint.

Stew [Stewart B. Leavitt, MA, PhD],

I would greatly appreciate if you could post the PROP/Public Citizen Press Release on the FDA petition [see below]. I think the press release makes clear that the purpose of this effort is to prohibit drug companies from promoting long-term use of opioids for conditions where use has not been proven safe and effective.

Please also let your readers know that the petitioners are not making a statement that long-term use of opioids for chronic pain or high dose opioids is always inappropriate. Several of the signers (myself included) prescribe long-term opioids. Our petition should NOT be interpreted as a manifesto on the appropriateness of long-term opioid prescribing for chronic pain. Instead, it should be understood as a request to FDA to better regulate the claims that opioid manufacturers can make about their products.

Stew — Your post (as well as others that have been critical of the factual statements included in the petition) suggests to me that you may be unfamiliar with the relevant federal law. The law places the burden on drug companies to prove that their products are safe and effective for the conditions that they promote them for. If drug companies want to make claims that opioids are safe and effective for long-term use in fibromyalgia, low back pain, migraines, etc., then they should do their homework and prove their case. It’s not the public’s responsibility to demonstrate the specific conditions where medications may not be safe and effective.

— Andrew [Kolodny, MD]

Here is the press release, posted at the Public Citizen website [here] on July 25, 2012…

Doctors, Researchers and Health Officials Call on FDA to Change Labels on Opioid Painkillers to Deter Misprescribing
Drug Companies Should Not Be Permitted to Advertise Long-Term Opioids for Non-Cancer Pain, Experts Say

WASHINGTON, D.C. – Labels on opioid pain medications should be revised to prevent overprescribing, a broad coalition of doctors, researchers and public health officials said in a petition filed today with the U.S. Food and Drug Administration (FDA). If the requested changes were adopted, drug companies would not be able to claim that the pain medications are safe and effective for long-term use by non-cancer patients.

According to the petition, opioid labels are overly broad because they fail to limit opioid use to severe pain, to include a time frame for use and to specify a maximum dose. Presently, the label on opioid analgesics simply states that they’re approved for “moderate to severe pain.”

The petition, available at, is signed by 37 prominent experts, including leaders in the fields of pain medicine, addiction and primary care; health commissioners; researchers; and program directors at public interest groups.

The requested changes relate specifically to when opioids are used for non-cancer pain. The petition calls for striking the term “moderate,” adding a suggested maximum dose equivalent to 100 milligrams of morphine and adding a suggested duration of use. The petition’s co-signers believe that preventing drug companies’ aggressive promotion of these medications for moderate pain will help curtail overprescribing. According to the Centers for Disease Control and Prevention, excessive prescribing of opioid analgesics is fueling an epidemic of addiction and overdose deaths.

Drugmakers prefer a non-specific FDA-approved label because it allows them to encourage use of opioids for an indefinite period of time and for a wide range of common problems. The proposed label changes would have serious implications for drugmakers because federal law prohibits “off-label” advertising. Drugmakers wouldn’t be able to promote opioids for continuous long-term use by people who don’t have cancer.

The coalition of experts who signed the petition believes that the label must be changed to reflect existing medical evidence. The long-term effectiveness and safety of opioid analgesics has not been established by scientific studies, and recent research calls into question the safety and effectiveness of these drugs when used long-term, particularly at higher dosage levels.

The FDA typically approves conditions that a drug can be used to treat on the basis of clinical trials that are 12 weeks in length. In the case of opioid analgesics, Dr. Edward Covington, director of the Neurological Center for Pain at the Cleveland Clinic, believes that short-term studies like this are inadequate. According to Dr. Covington, “It’s clear that the short-term effects, on the basis for which they are approved and marketed, do not mirror their effects in long-term use. In the absence of long-term studies demonstrating safety and effectiveness, we need limits on what drug companies can claim about opioids.” Covington also believes that suggested dose limits must be added to the label “given the lack of experimental support for using high doses.”

Although the proposed label changes would limit the way drug companies promote opioid analgesics, doctors would continue to be able to make prescribing decisions based on their clinical judgment, assessment of patient needs and response to treatment. “Off-label” prescribing is considered appropriate, even though “off-label” advertising is prohibited. According to Dr. Jane Ballantyne, a pain specialist at the University of Washington in Seattle and a co-signer of the petition, “A form of constraint that controls overuse while preserving opioids for patients in need can only be a positive step towards more rational and safer prescribing.”

Dr. Lewis Nelson, an emergency physician and medical toxicologist at NYU Langone Medical Center, explained that “It’s time to close the loophole on opioid labels,” which he says amounts to “a mechanism that allows drug companies to promote opioids for unproven uses.” Physicians are wrong to assume that “on-label” indications are evidence-based with regard to safety and efficacy.

Over the past 15 years, Purdue Pharma, maker of OxyContin, and other opioid manufacturers have sponsored a campaign to encourage wide-scale, long-term prescribing of opioids for common chronic conditions like fibromyalgia and low back pain. Previously, doctors had been reluctant to use opioids long-term because they were worried about causing addiction. But company-sponsored education misled doctors to believe that addiction was rare and that withholding opioids was cruel.

“Over-prescribing of opioids is harming many chronic pain patients,” Covington said. “The label change is a way for the FDA to let the medical community know that risks may outweigh benefits when used long-term.” He continued, “The issue is tricky, because a subset of chronic pain patients benefit from chronic opioids, usually in low to moderate doses, and it is important that access is not restricted for those who show lasting benefit. The label change we’re requesting balances the need to preserve access for these patients with the need to reduce overprescribing.”

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SB. Leavitt, MA, PhD said...

Dear readers: I felt it would be inappropriate to clutter Dr. Kolodny’s response (above) with my own comments. As I noted to him in a personal response to his e-mail, perhaps there may be some relevant points in federal laws and regulations under FDA purview raised by the PROP Petition that I (and others) do not fully appreciate. As I hope I made clear in my UPDATE earlier today [here], I like law, and I like the use of good and valid scientific evidence as proof in reaching fair and equitable judgments that affect patient health and well-being.

I hope that Dr. Kolodny, his colleagues, the rest of the pain management community, and the FDA will be engaging in much further open dialogue to explore and clarify the important issues of concern in the Petition.

Anonymous said...

I cannot even begin to express how thankful I am for your efforts each time I read your newsletter.... And I'm certain I am just one of millions who feel the same who have not found your newsletter yet who have been through the nightmares....

I was actually thankful when brain cancer was diagnosed as doctors treated me differently, with compassion, and without fear to treat my pain. Unfortunately the pain that led to the brain cancer was diagnosis as CSF leak because now I am back to being viewed in the other category.......

If a chronic pain patient is diagnosed with cancer you breath this giant sigh of relief because the doctors will treat you kindly and actually feel comfortable treating your pain.... At least while you have the cancer in your system. Perhaps there can be a negotiation point in the legislation that doctors must leave a cancer tidbit to allow medication to be subscribed and pain to be treated. It would be with the same oddity the entire system is regulated at this time.

Anonymous said...

Where are all the patients who are being harmed by opiate medications? Why don't they list case studies and testimonies? Also, why is PROP collaborating with addiction specialists? A lot of addiction specialists do not have medical training. They are usually psychologists or modern day snake oil salesmen attempting to profit off of a non-issue.

Also, Dr.Kolodny is being pretty evasive for a person who claims to have so much evidence for his position. Also, why is the burden of proof on the pharmaceutical companies? The pharmaceutical companies have done clinical trials that were approved by the FDA. Why should they have to do more? Since Dr. Kolodny is making claims with what appears to be little evidence, the burden of proof is on him.

It is very easy to think about this in legal terms. Dr.Kolodny is the prosecutor and the pharmaceutical companies are the defendants. It is up to the prosecutor to present and explain evidence in order to get a conviction.

Also, as a scientist myself, I find it disgusting and unprofessional to say in essence "I don't have to prove anything. That is not my job." That is precisely the job of every scientist. That would never fly in any other field of science, so I don't know why Dr.Kolodny believes that is appropriate thinking for a doctor.

Anonymous said...


All I can say is that I have the fear that if any of the PROP supporters suggestions make their way into product labeling, I fear the chilling impact it will have on insurance coverage of the drugs in the long-term. As your reply to the initial PROP proposal mentioned, any change that would make long-term prescribing of more than an equivalent of 100mg/day of oral morphine for longer than 90 days considered to be off-label prescribing, would allow insurance companies to even more easily than they do now with more substantial reasons, to stop coverage of long-term high-dose opioid therapy. I still want to know their justifications for these totally arbitrary cut-off points other than, "Well, that's what the State of Washington did," for example. Well, that's not quite true even, so there goes that one. I could go one endlessly about this point alone.

I have been a patient at the Cleveland Clinic, where one of the PROP leaders is the head of the Neurological Center for Pain there. That is the place that got me walking again and although the surgeon who did the work on me is no longer there, I still consider them miracle workers and when I do need additional surgery, I will be back there again since I live in Ohio. However, with three major spine surgeries came the need for long-term high-dose opioid therapy as a result. It's listed as a possible consequence of my surgeries done -- new or increased pain. I never hurt before my first spine surgery. Sometimes people at places like the Cleveland Clinic lose sight of the day-to-day ability of the common patient to get care and coverage for procedures. I know from my experiences that the Cleveland Clinic Foundation has a very generous charity program and even with my insurance, because of my low income, out of a bill in excess of $250,000, I only paid $125 (I was originally required to pay a $750 co-payment by MA plan). I don't get that help locally. I have to pay full prices for treatment because my local hospital and physicians do not have the charity pull of such a large institution that can "foot the bill" of its patients in order to further their real desire to help and to get international attention and acclaim for their breakthrough work. It's just not a perfect system we have and we all know it. But when making suggestions that affect those outside of their walls, they need to keep those of us who don't have daily access to the charity resources of the Cleveland Clinic Foundation and such places in mind. I do not personally believe that many of those who signed the PROP petition have any clue of what an average patient might have to pay for extended non-traditional modalities of treatment that even if covered by insurance, are covered in limited amounts.

This PROP group needs to think long and hard about the impact of what their solution is to what they see is a problem. There are other ways to accomplish similar goals without making long-term high-dose opioid therapy off-label prescribing. I pray it never happens for not myself, but the millions who will suffer because of it and hope those on the PROP petition will then have to carry some of my pain every single day from them on for the rest of their lives.

And don't get me started on what even the current reformulations of OxyContin and Opana are doing to cause a major increase in the number of heroin-related ER visits and deaths. Every change in how we do things now has a opposite result that can't always be predicted. Did some people see the heroin issue coming? I actually made a comment to my wife that an addict will find their drug somehow, even if means changing to something far more dangerous when I heard of the reformulations. They are filling the needs of their disease of addiction. I pray for their well-being, too. Come down here with the rest of us, PROP supporters! You have your heads too high up in the clouds to understand the impact of what you suggest.

Anonymous said...

As an American and a chronic pain patient, it is my right to choose which medicines I want to take. If my physician believes that opioids are worth trying, then I will try them.

Why should I have to listen to doctors that are not treating me and are not in a position like mine? I believe that everything PROP believes is false, based on the evidence I have seen. It is my choice to use opiate pain medications. If those medicines turn out to be dangerous, oh well. I have a right to choose which medicines I want to take. It is fundamentally un-American to try to force another persons medical beliefs on another.

Why is PROP on such a witch hunt against opoiods? There are many dangerous new age and religious "therapies," that are far more dangerous. Why doesn't PROP go after energy healers, chakra aligners, faith healers , and people that attempt to use prayers?

Also, opiate medicines have been used for centuries. There are a lot of pain patients who have been on them for more than twenty years. Why don't we track those people down and do case studies on them? The evidence is there if PROP would get off it's high horse and do some real science.

Anonymous said...

Do these people who support this petition even realize that they will be practically forcing what are now legit pain patients to go to the streets for relief? To get adequate pain relief, many who are on long term opioids will now go to the streets to get adequate pain relief, so therefore will not be monitored at all. What do they think death rates will be then? This is some of the most backward thinking I have ever heard of from supposed learned men!! Have they lost touch with actual patients that much? Have they become that biased? What they propose is cruel and will do NOTHING to stop the illegal drug trade on the streets and will ONLY hurt and demean legitimate pain patients, force Drs into not being able to help them, and they WILL have to turn to getting their medications from the streets for adequate relief. It will be just like the "unintended" responses to changes in formulation of certain long acting drugs and the rise of heroin related overdoses and deaths! There are many chronic pain patients out there who are living a more productive better quality life because of these medications. They should not be punished because of the poor CHOICES of others to misuse their medications or someone elses medications. There is definitely a problem with recreational use of these drugs but I dont think restricting their use so harshly to everyone is the answer to getting them off the streets. It is hard enough now for most pain patients to get relief and to be taken seriously and to be believed that they have pain. Most Drs already treat most patients akin to criminals. This will just further tie their hands. Most Drs are not going to prescribe "offlabel" nor are most insurance companies going to allow it. Drs need to be better taught how to manage chronic pain and step up to the plate to do better education and monitoring.

SB. Leavitt, MA, PhD said...

While comments from patients like those above are always welcome, you should realize that you are “preaching to the choir” regarding this issue. What you should be doing is submitting your comments to the FDA (instructions and the URL link were provided in my prior UPDATE [here]), or make your concerns known to Congresswoman Mary Bono Mack [go here].

Anonymous said...

As the chairman of the Indiana Pain Society, I find the PROP position ridiculously naive, thinking that they are only requiring opioid manufacturers to change the labeling of the opioid medications, and this would have no effect on availability. The entire point of the PROP petition is restrict availability, otherwise why have such a petition. If these physicians had a clue as to how the real world works, they would understand package inserts and labeling have a direct effect on availability, and in the current regulatory environment physicians are very likely to restrict their prescribing to on-label for opioids. Insurers will also restrict payment for such medications requiring on-label prescribing in order that these medications are covered financially. There is simply no reason why a mindless approach as was adopted in Washington State would be imposed on pain patients throughout the country. This is effectively identical to outlawing cars because cars kill people or outlawing guns or alcohol because they kill. It is a very heavy handed approach that assumes elimination of all risk of death from opioids by elimination of opioids for chronic non-malignant pain is more important than the treatment of chronic pain. The petition and the position of PROP is untenable, naive, and extremely damaging to the chronic pain community.
Michael L. Whitworth, MD

SB. Leavitt, MA, PhD said...

Thank you, Dr. Whitworth, for your comments -- I hope you also have shared them with the FDA. I raised some of the same concerns in my prior UPDATE editorial, regarding insurance converage and off-label Rx, and it is always good to have a second opinion.

Anonymous said...

In response to the question, "Where are all the patients being harmed by opiate medications?"
Several thousand, per year are in their graves, from accidental overdose death. For each of these, there are dozens more admitted for nonfatal overdose. I am amazed that this question is repeatedly asked!

SB. Leavitt, MA, PhD said...

In balance to the comment immediately above, it seems fair to wonder how many people are in their graves due to the physical toll of unrelieved chronic pain, or from suicide when their undertreated pain became unbearable.

ALSO… we highly recommend that readers examine the recent response to the PROP Petition from the American Academy of Pain Medicine [PDF available here].

Anonymous said...

To the person above, who answered my question with "Several thousand per year....question is repeatedly asked." Can you give the links for the stats you claim? You can't answer a question that demands proof with no proof. Your short answer is not good enough.

Also, accidental overdoses are listed as possible adverse effects in the patient information that comes with the medicine. It is a risk that all patients should be aware of because it is printed on the medicine container and on the medication insert.

Furthermore, if those patients would have followed the directions of the pharmacist and the doctor, they would not have overdosed. Why should we ban or limit medicines because people cannot or will not follow directions? We should not have sympathy for drug abusers or people who don't follow directions.I certainly don't.

Nobody is forced to buy any type of medicine, including narcotic pain medication. By purchasing narcotic pain medicine, you are implicitly agreeing to follow the prescribing rules and to suffer the consequence should you be allergic or have adverse reactions including overdose or death.

So, why don't you grow up and force people to be responsible, instead of catering and babying to irresponsible people?

Anonymous said...

Ive been on opiates for 23 years now and have had no side effects.
I walk 4 miles a day ,work on my computer just like a normal person.
I dont know why all the fuss.
Sounds like Andrew is trying to make a name for himself.


Anonymous said...

This situation with opiates is not new ,its been around for thousands of years. Pharmaceutical companies that make these products are now making time released forms like OxyContin ,people that are abusing this medication causing death.
One does not realize that one 80 mg
OxyContin pill is equal to 16 percocet less the Acetaminophen.
So they wonder why thier heart goes pitter pat after chewing up a
80 mgs OxyContin pill then that person stops breathing. You must understand the anatomy of the body
and your respiratory system.
Stop the abuse and the deaths will decrease.


Anonymous said...

Dr.Kolodny's proposal that drug companies prove that opiate medicines are safe for long term use is unreasonable and insincere. Where are the pharmaceutical companies going to find patients willing to test medicines for twenty years or more? Clinical trials are expensive and difficult to do already. How in the world are you going to find enough people to show up consistently for twenty years? A lot of things can happen during that time. It is hard enough to control variable factors for short term trials. Long duration trials would be a nightmare for anyone involved.

What does Kolodny want drug companies to do next? Test millions of patients to find out how often rare and bizarre side effects happen? Kolodny is basically suggesting something that he knows is impossible, so he can ramble on about "no evidence."

The pharmaceutical companies do not specifically claim that the medicines are safe for long term use,anyways. Therefore, they do not have to prove it. It is sort of an intellectual stalemate because Kolodny is making a negative statement and the drug companies are making a neutral statement, if anything. In fact, Kolodny himself admits this when he states that "the labels are intentionally vague." So, really nobody has to prove anything. Despite Kolodny's ridiculous statement that the government requires the drug companies to. Yeah, they would require them to if they ACTUALLY MADE THAT CLAIM! Kolodny needs to take some philosophy classes because any philosophy undergrad would know that you can't prove something that you do not positively claim.

How do people like him become doctors when they have such terrible reasoning skills? Maybe the MCAT should add a philosophy section and a more intense math section. Some linear algebra and real analysis would do kolodny's brain some good.

Anonymous said...

Dr. Leavitt, I'd love to hear your thoughts on Probuphine. It sounds like a promising delivery mechanism that could make its mark on opioid dependance and (eventually) chronic pain. Thank you.

SB. Leavitt, MA, PhD said...

Probuphine is a subcutaneous implant containing buprenorphine, capable of delivering continuous and persistent, around the clock blood levels of the drug for 6 months. It is nearing completion of testing as a treatment for opioid addiction and is intended to enhance patient compliance and retention in treatment. This same sort of approach was used for naltrexone implants, recognizing that a most difficult aspect of opioid addiction treatment is patient compliance with therapeutic regimens.

The buprenorphine implant is not being tested for analgesic use as far as I know. There already are sublingual tablet and patch forms of buprenorphine available, with the patch being FDA-approved as a long-lasting, sustained-release analgesic. I’m not certain what advantages, if any, an implant would have over the patch when it comes to use for pain relief.

Anonymous said...

Ive seen T.V. adds on the off label of Cymbalta for chronic pain.
What happens is people get so spaced out on this drug,they forget they have chronic pain.Do we hear from PROP complaining about this,no, why, becuase its not a opioid.No matter how much PROP wants to strike opioids for Moderate pain ,your wasting your time.Is there a ceiling dose when a person becomes tolerant over a period of time to any one opioid.
Sounds like Dr. K. is talking out of both sides of his mouth,wanting to chnage the lableing on opiates when he has no business making such statemnet until he knows what its like to suffer every day in chronic pain,cancer or not,it doesnt matter chronic pain is chronic pain.
I think the press release makes its clear that the purpose of this effort is to leave drug companies alone and let them go ahead and promote long-term use of opiods for condtions where Pain Docs.see fit.Ive used opiates with response to my doctors orders for 20 plus years. i just had blood test done and my kidneys and liver are fine.
Thats proof enough for me Dr.K.


Anonymous said...

The funny thing is Andrew Kolodny is not a pain management doctor or specialist. He is a psychiatrist. I sincerely doubt that he has ever treated people with severe pain from cancer , horrible diseases, and accidents. His opinion on pain medicine should not be considered at all because he is not even practicing in that area.I thought it was illegal to give medical advice or to practice medicine out of your specialty. Obviously, Kolodny is not physically being a pain doctor, but he sure acts like one when he speaks or writes articles.

Anonymous said...

Andrew Kolodny ,

Seems you lost, better luck next time, if there is a next time.