Giving Thanks for the gifts in my life

havest thanksgiving holiday seasonThis Thanksgiving day I have so much to be thankful for but I will focus on one very special gift. I am thankful for having my family together, healthy and whole. Before my daughter found her way to sobriety I wondered when I would ever have a holiday when I wasn’t sad, I longed for my family to be together and happy again. Yet piece by piece here we are. My daughter is over 5 years clean and sober. We are all healthy. This is a joyful time for our family.  I realize that life is constantly changing, whether you want it to or not so I relish these moments. I am so filled with gratitude.

Also on this day I pray for those loved ones who have not found their way to recovery. I pray for their safety and that they find their way to recovery and back to the ones that love them so dearly. I pray that even if for just one moment they have the clarity that they need to want sobriety no matter how difficult the journey. I pray for those in recovery that they stay strong in their commitment to a life of sobriety.  And, lastly, I pray for the parents who have lost those they hold most precious. I pray that they find comfort, healing and support.

What’s Thanksgiving to the Parent of and Addict?

What a question. What does the parent of an addict have to be thankful about?

I remember the horrors of holidays. It seems no matter the occasion Thanksgiving, Christmas, Birthdays or anything that was special to our family our son while he was using found a way to bring heartache and sorrow to the occasion.

Why couldn't he just be OK for one day? Why do we have to have every holiday and special occasion ruined? These were the constants in our life.

Looking back it is easy to remember these events. A son showing up on Christmas Eve while we were walking out the door. Drug dealers delivering heroin to our home on Christmas Eve as casually as a pizza delivery person. Thanksgiving not being able to rouse him to join us for lunch. Going down to a prison located 125 miles away on Thanksgiving eve to pick him up after being released. Every holiday was an event.

The perspective of time and distance allows me to understand most all of our anguish and hurt was self imposed. We EXPECTED what was impossible to be delivered. My son was an addict. My son was addicted to drugs and I didn't understand addiction and what it meant.

My son suffered from the disease of addiction. He did what addicts do and all that is expected of an addict. He used drugs no matter what I wanted or expected. My heartache and anger was self imposed. I expected from him something he didn't have to give. At least not at that time.

If your loved one is suffering from addiction accept the reality of what IS and don't play a game with yourself of OUGHT to be able to be good for one day.

Secrets from a father about for surviving a holiday with an addicted loved one would include:

  • Temper your holiday expectations. 
  • Accept what is given.
  • Love with no return expectation.
  • Do not expect something from someone that they do not have to give.
  • Inside there is still a person. You loved them all their life, do not forget.
  • Where there is life there is hope. Look around you and see the life.
Never stop believing. Tomorrow my son will be joining us with his family. Hugs will be shared. We will give thanks to all and each other. 6 years ago if anyone would have told me this day would come I would have thought they were crazy. Never stop believing in yourself or others.

Happy Thanksgiving to all.

Buprenorphine Diversion: Beyond a Superficial Understanding

First Posted 11/19/2013

In ‘Addiction Treatment with a Dark Side’, Deborah Sontag of the New York Times shared her observations of the clinical use of buprenorphine for treating opioid dependence, warts and all.  Readers of the Talk Zone know my bias—that buprenorphine/Suboxone is one of the only effective treatments for opioid dependence, and many patients are best-served by long-term, perhaps life-long treatment with buprenorphine.   But I read the article the article with interest because I know that Ms. Sontag ‘did her homework’, including visiting a number of practices, speaking with a number of patients, and reviewing hundreds of studies about buprenorphine and Suboxone over the course of many months.

From my perspective, the article overstates the diversion problem.  In my last post I asked if the fear of diversion should be a factor in whether buprenorphine-based medications become the leading edge of addiction treatment.    I stated my opinion—that if overdose deaths don’t pull acetaminophen from pharmacy shelves and diversion doesn’t keep hydrocodone off the market, then diversion of buprenorphine deserves little discussion relative to the value of buprenorphine treatment for addiction.

With the wave of stories describing buprenorphine as ‘controversial’, every discussion of the medication seems to revolve around diversion.   Do the numbers support the association? Deaths from Suboxone—deaths where buprenorphine was one of the drugs that caused death—amounted to several hundred over the past ten years, compared to 38,000 drug overdose deaths in 2010 alone.  The magnitude of the difference is so staggering that it deserves repetition; 400 deaths in ten years, vs. 38,000 deaths in one year.  The total number of deaths linked to buprenorphine over the past ten years is about equal to the number of people who die from acetaminophen– EACH year.

Diversion of buprenorphine is a complex issue.   Words like ‘diversion’ and ‘overdose’ are loaded with so much emotion that one word seems to tell the whole story.   A Google search of Suboxone brings up news reports such as ‘Suboxone found at overdose scene’, or ‘man arrested with cocaine, heroin, and three Suboxone tablets.’  The stories create an ugly image, with buprenorphine/naloxone as one more drug of abuse, found at ‘an increasing rate’, according to other headlines. But a superficial look at diversion yields a superficial understanding of the diversion problem.

Take as example a patient has not used illicit substances for 3 years while taking prescribed Suboxone, who relapses to heroin and dies from overdose.  News stories will describe a scene littered with needles, heroin, and Suboxone tablets.  That description creates a misleading impression of the patient’s history, and a misleading impression of buprenorphine.  Even if the story provides more detail, the headline alone will fill the tweet—the ‘news’ of the modern era.

Is the nature of diversion, the reason for diversion, or the consequence of diversion relevant to discussions about the diversion of buprenorphine?  If someone tries to hold life together by purchasing street Suboxone in a geographic region void of certified physicians, should that ‘diversion’ be included in the category as the sale of oxycodone?

What if the powerful mu-receptor blocking effects of buprenorphine have positive effects?  What if studies found a lower rate of overdose deaths in communities with greater diversion of buprenorphine?   Would that be relevant to the diversion discussion?

I do not know of any evidence that diversion of buprenorphine correlates with fewer overdose deaths.  But many public health experts predict that encouraging ‘street use’ of naloxone would reduce overdose deaths, so expecting the same from buprenorphine, a stronger and longer-lasting mu antagonist, is not unreasonable.

Patients on buprenorphine awaiting elective surgery discover that the blocking effects of buprenorphine last for weeks.  The same patients report that even after several weeks off buprenorphine, significant doses of oxycodone will relieve post-op pain, but won’t provide the ‘euphoria’ oxycodone used to provide.  Patients who could never make a week’s script for oxycodone last longer than a day can often control use of opioid agonists after surgery if kept on a small dose of buprenorphine.    Considering these findings, it is not unreasonable to wonder if there is a lower risk of death by overdose in people who ‘divert’ buprenorphine.  Buprenorphine has a much longer half-life than oxycodone or heroin, so diverted buprenorphine intended for use ‘in between’ acts as a blocker during periods of active heroin use.  Is it possible that traces of diverted buprenorphine in the bloodstream saves lives?  If so, is that relevant to discussions about diversion?

The worst diversion scenario is if opioid-naïve people take buprenorphine or Suboxone and becoming addicted to opioids as a result, i.e. diverted buprenorphine serving as a gateway drug to opioid dependence.  Nobody should take that situation lightly.  But stories from the streets bring to mind biological programs where sterile males of an invasive species are released into the wild in effort to eliminate the invasive mosquito, lamprey eel, or fruit fly.  What if the spread of buprenorphine functions as an ‘addiction moderator’ where the more buprenorphine in a community, the lower the rate of overdose deaths?

I realize that I am out on a limb— but as the saying goes, that’s where the fruit is.   If buprenorphine diversion is investigated in a superficial manner, we will collect nothing but superficial results.  The diversion of a medication with the potential to save as many lives as buprenorphine deserves a deeper level of understanding.

Treatment Resistance in Eating Disorders

Clinicians treating patients with eating disorders find the challenge great with many treatment-resistant cases.

To some extent, this is true of any clinical disorder. Outpatient treatment rolls and inpatient samples are over-represented by those failing to respond to initial interventions.

A medical example is helpful here. Endocrinologists specializing in diabetes see more complicated cases where glucose control is difficult and diabetic complications are common.

Diabetics with easy glucose control and no complications do not need to see an endocrinologists. To an endocrinologist, clinical practice seems to point to the disease as a treatment-resistant and clinically challenging disorder.

Nevertheless, treatment resistance in eating disorders is a significant issue that has been recently summarized in a nice review by Dr. Katherine Halmi.

Here are my notes from review of the Halmi manuscript using her key headings:

Core eating disorder psychopathology

  • Adolescent eating disorder subjects lack insight into the seriousness of illness
  • Many do not acknowledge need for treatment
  • Body weight, exercise and dieting provide a distraction from other life problems
  • Malnutrition in eating disorders contributes to cognitive impairment, treatment engagement problems
  • Bulimia treatment resistance has been linked to greater depression, lower BMI and social adjustment problems

Psychiatric and psychological comorbidity

  • U.S. National Survey found high rates of psychiatric comorbidity in eating disorders (56% in anorexia nervosa, 95% in bulimia nervosa and 79% in binge eating disorder)
  • Anxiety disorders rates are elevated in eating disorders with obsessive compulsive disorder and social anxiety disorder two common conditions
  • Anxiety disorders can contribute to resistance of treatment of eating disorder symptoms
  • Cluster B personality disorders are elevated in bulimia nervosa and appear related to higher rates of substance dependence in this disorder
  • Perfectionism is common in anorexia nervosa. Early onset and high perfectionism traits contribute to higher treatment resistance

Biological features

  • Serotonin receptor and transporter function appear to influence course of illness in eating disoders
  • GABA receptor genotype appears to be related to level of trait anxiety in both bulimia nervosa and anorexia nervosa
  • GABA receptor abnormalities are also possibly related to treatment resistance

Treating refractory patients

  • Quetiapine, olanzapine, haloperidol and duloxetine are drugs with some promise in treatment resistant anorexia nervosa
  • Novel psychotherapies including CBT and the Maudsley Model  target key features of resistance in anorexia nervosa
  • Treatment resistant bulimia nervosa may respond to sequential treatment strategies that include partial hospitalization, selective serotonin reuptake inhibitor (SSRI) drugs and cue exposure
  • Binge eating disorder may respond to high dose SSRI therapy or topiramate in a graduated dosing schedule

This review points to the key elements for treatment of the difficult eating disorder patient.

This population needs access to specialized hospitalization units, psychopharmacology expertise and specialized psychotherapy services.

Dr. Halmi notes advances in the treatment of this population may require advances in understanding the neurobiology and neurocircuitry for the disorder.

Readers with more interest in this summary can find the free full-text manuscript by clicking on the DOI link in the citation below.

Winter snow scene is from the author's files.

Follow the author on Twitter @WRY999

Halmi, K. (2013). Perplexities of treatment resistence in eating disorders BMC Psychiatry, 13 (1) DOI: 10.1186/1471-244X-13-292

Pain into gain for parents of addicts and alcoholics

reaching the final strawAddiction can be a transformative experience. I never imagined that I would give thanks for the gifts that addiction has given me, but I do. I give thanks, and I am grateful for the experience (although I would never wish it on my worst enemy). My son’s illness puts many things into perspective or shines a new light on gifts previously unseen or unappreciated. Here are some of the items on my thanksgiving list:
Support from friends and strangers who became friends
The opportunity to meet wonderful people in the recovery community
Compassion for others
An appreciation for each and every day
A kinship with other parents
Gratitude for guidance along the way
Appreciation for resources to smooth the path to recovery
Some very good reasons to stop judging others

Straw into gold, pain into gain….what’s on your list?

Congress Passes the Sunscreen Innovation Act to Speed up FDA’s Review of Time and Extent Applications for Sunscreen Ingredients and Other OTC Ingredients

By Riëtte van Laack

The House of Representatives on Nov. 13 unanimously passed the Senate version of the Sunscreen Innovation Act (SIA), S. 2141.  The Act is currently before the President, who is expected to sign it.  The SIA amends the Food, Drug, and Cosmetic Act to provide specific deadlines for FDA’s review of time and extent applications (TEAs) for sunscreen ingredients and to require FDA to set specific deadlines for review of TEAs for non-sunscreen ingredients.  For background information on TEAs, see our previous post here

The SIA details timelines for FDA review of currently pending TEAs for sunscreen ingredients as well as for review of new TEAs submitted after enactment of the law.  Eight sunscreen TEAs have been under FDA review, with some pending for more than a decade.  In 2014, FDA stepped up its review efforts and issued response letters for five of the TEA applications.  Under the SIA, these five response letters  are “deemed to be . . . proposed sunscreen order[s] and [must] be displayed” on FDA’s website and “announced” in the Federal Register within 45 days of enactment of the SIA.  The pending TEAs which have not yet been reviewed must be reviewed and a proposed order for each must be published within 90 days of enactment of the SIA.  The table below shows the timing for these pending TEAs.  If FDA makes a determination that the substance is generally recognized as safe and effective (GRASE) or not GRASE based on sufficient data, the timing is predictable; a final order must be issued 135 days after publication of the proposed order.  However, there is a risk of “slippage,” in those cases where FDA determines that “data are insufficient to classify as GRASE” and additional information is necessary to allow a determination as to the status of the ingredient.

Outline of timing for new sunscreen TEAs pending
(and found eligible) before the enactment of SIA


45 days after SIA becomes law for TEAs with response letter before SIA.

Proposed Order:

90 days after SIA becomes law for TEAs without response.

Comment Period:

45 days

Meeting Request:

Sponsor may request meeting within 30 days after proposed order.  FDA must grant meeting within 45 days after date of meeting


FDA may convene advisory committee (adcom).

Final Order:

90 days after closing of comment period, if sufficient data to determine GRASE/not GRASE.

210/270 days after receipt of data from sponsor, if insufficient data to make determination if GRASE; 210 days if no adcom convened, 270 days if adcom convened.

For new sunscreen TEAs, the SIA also sets specific timelines for FDA’s determination whether a sunscreen TEA is eligible for review and FDA’s substantive review of the TEA.  The outline below shows the timing for such new TEAs.  Although there are specific deadlines for FDA review, etc., there is a possibility for slippage in the determination of the eligibility and in instances where FDA determines that additional information is necessary to allow a determination whether the ingredient is GRASE.

Outline of timing for new sunscreen TEAs submitted after the enactment of SIA

Eligibility Determination/Filing of Request:

Within 60 days after sponsor’s submission of data in support of GRASE determination, FDA must determine whether data are sufficient to file request.

FDA Refuses Filing of Request:

Within 60 days after sponsor’s submission data, FDA refuses filing. Sponsor can request meeting within 30 days of refusal.
FDA must convene meeting within 30 days of date of meeting request.

  • FDA files request within 60 days after meeting or
  • Sponsor may submit additional data and elect to file request over protest within 120 days;
  • FDA must file request over protest within 30 days after sponsor’s election.

Data Submission for Filed Request:

FDA will provide no less than 45 days for comments related to TEA that has been found eligible.

Publication Proposed Order:

Within 300 days after request is filed.


FDA may convene adcom during these 300 days.

Comment Period

45 days

Meeting Request:

Sponsor may request meeting within 30 days after proposed order; FDA must grant meeting within 45 days after date of meeting request.

Final Order:

90 days after closing comment period, if sufficient data to determine GRASE/not GRASE. 

210 days after receipt data from sponsor, if FDA determined that data were insufficient to make determination if GRASE.

Once FDA has issued a final order that the sunscreen ingredient is GRASE, it may be marketed.  At a later time, but within 5 years after the enactment of the SIA, FDA may amend the sunscreen monograph to include the new active ingredients subject to final orders.  (Once included in the final monograph, the final order for the sunscreen ingredient will cease to be effective).

Whether the SIA will in fact result in more sunscreen ingredients being available remains to be seen.  The SIA sets deadlines for FDA’s review.  However, it does not require that FDA find the ingredients to be GRASE.

Although named “Sunscreen Innovation Act,” the act also addresses TEA reviews for ingredients that do not fall under the sunscreen monograph.  For TEA applications for non-sunscreen active ingredients, the act requires that FDA issue proposed regulations with timelines for TEA reviews within 18 months after the SIA has been signed into law.  Sponsors of pending non-screen ingredient TEAs that have already been found eligible for evaluation of inclusion in the relevant monograph can ask FDA to provide a review framework for their TEAs rather than wait until FDA issues the regulations.  Such requests must be made within 180 days of enactment of the SIA.  FDA’s timelines “may vary based on the content, complexity, and format of the application” and must reflect public health priorities and “take into consideration[,] the resources available to [FDA].”  In light of the requirements for sunscreen ingredients and FDA’s other obligations (e.g., finalizing the monograph for antimicrobial substances), it may well be years before these TEAs will be reviewed.

Killing the Suboxone Gift Horse with Naltrexone

First Posted 11/14/2013

I received an email update today with important news from the world of psychiatry and addiction.  The email highlighted a study from the October issue of Jama Psychiatry, entitled ‘A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers’.  The study compared relapse rates in opioid addicts who were tapered off buprenorphine at different rates.  The study considered success as being free of opioid use and taking naltrexone, an orally-active opioid antagonist, after 12 weeks.  The study found that 50% of the people tapered off buprenorphine over 4 weeks were abstinent and taking naltrexone.  That compared to 21% and 17% of success in patients tapered over 1 or 2 weeks, respectively.

I’m sorry, but who cares?

Regular readers of my blog know my opinion about buprenorphine.  (Newcomers please note that by buprenorphine I mean buprenorphine, Suboxone, or Zubsolv, since they all work in identical fashion).  Most people who work in the addiction field agree that addiction is a life-long illness.  Most people who have worked in the field for a few years or more know that relapse is a common feature of opioid dependence.  I believe that anyone claiming to ‘cure’ opioid dependence through use of a plant, root, amino acid, vitamin, hypnosis, accu-pressure point, or 90-day program is either misinformed, pathologically optimistic, lying, or blinded by profit motives.

Opioid dependence is associated with a high rate of death and morbidity. Beyond buprenorphine, the only reliable intervention for treating opioid dependence is methadone maintenance, if ‘reliable’ is defined as ‘likely to be successful.’  I realize there are hundreds if not thousands of residential treatment facilities throughout the US that advertise ‘freedom from addiction’; some even offering freedom from ‘addiction’ to buprenorphine.  These claims are made, and apparently believed, even with one-year relapse rates greater than 90% in opioid addicts treated without medication.  In the real world of ‘Suboxone Talk Zone’, I have to burst a few bubbles about ‘sending someone to treatment.’    For opioid dependence, treatment without medication yields long-term sobriety in only a small minority of patients.

Yet many healthcare professionals continue to chase after the golden goose of abstinent recovery.  Makes me wonder if laetrile would still be around with better marketing!

Before buprenorphine, opioid dependence was an oft-fatal illness that in most people responded only to the administration of opioid agonists at frequent intervals, with no patient autonomy and the threat of discharge if anything prevented on-time arrival at the early-morning line-up.  In 2003, along came buprenorphine— a prescription medication with a reasonable generic cost (finally), with few or no long-term risks and tolerable side effects, that eliminates cravings and prevents illicit opioid use in 50% of an average study population of opioid addicts who are allowed to continue their medication.  So why, exactly, are we excited by the prospect of changing from buprenorphine to a medication that carries the risk of hepatic necrosis?

Are people on naltrexone better off than people taking buprenorphine?  One would hope so, given that 50%-83% of people in the current study went back to active using while trying to make the switch!  Patients on naltrexone still have the problem of blocked mu receptors during emergency surgery.  Having blocked opioid receptors is an even larger problem for many educated addicts than their doctors realize, that goes something like this: ‘I stopped opioid agonists, but now I have to block my endorphins too?!

Why not just keep stable buprenorphine patients on buprenorphine?

The argument for naltrexone over buprenorphine comes down to two issues.  The first is the quasi-spiritual attitude that people are in an inferior form of treatment if their mu receptors are bound by even a partial agonist—no matter that those receptors have developed complete tolerance to the agonist effects of the drug.

The second argument focuses on diversion.  Buprenorphine is sold on the street, particularly in areas where there are no doctors certified to prescribe the medication.  People divert buprenorphine in a number of ways, ranging from efforts to get high, to use ‘in between’, to attempts at self-treatment.  But should risk of diversion reduce the legitimate use of a medication that has saved thousands of lives? Is it logical to throw the bupe-baby out with the bath water when deaths from buprenorphine are less common than deaths from acetaminophen?

I expect that the risk of diversion decreases over time in patients treated with buprenorphine.  Patients in long-term, stable treatment are more likely  employed and insured, with less financial incentive to sell controlled substances and more to lose for doing so.  Most of my stable patients develop insight into the damage caused by addiction, and have no interest in getting someone else caught in the same trap.  Most of the patients I’ve treated over time have severed their connections with the using world.  And most of them are grateful for a second (or tenth) chance at life; grateful enough to avoid risking everything by selling drugs.

Even if diversion could be blamed, in part, on stable buprenorphine patients, why is addiction treated differently than other diseases?  Diversion of opioid agonists is a greater problem than diversion of buprenorphine, both by sheer volume and by the damage from diversion, yet the FDA just approved another potent mu agonist in Zohydro—a drug with far greater diversion potential than buprenorphine or Suboxone.  If diversion doesn’t disqualify the pain meds used for strained backs, bumps, and bruises, why should diversion derail one of the only effective treatments for a disease that is killing thousands of young people?  Heck, pseudoephedrine is sold from pharmacies with a signature; the dangers of methamphetamine didn’t eliminate our collective concern for people with stuffy noses!

If we take diversion out of the argument—for example by deciding that the 300-odd deaths from buprenorphine diversion don’t warrant removing an effective treatment for a disease that has become the leading cause of death in young adults— the push off buprenorphine makes little sense.  I suspect that the people advocating ‘progressing’ from buprenorphine to naltrexone do not envision patients treated indefinitely with naltrexone either, but rather see naltrexone patients as somehow ‘closer’ to abstinence than buprenorphine patients.  From a neurochemical standpoint, what is the difference between being fully tolerant to a partial agonist vs. taking an antagonist?  For relapse-prevention, advantage goes to buprenorphine, since ‘effective relapse’ to opioid agonists requires buprenorphine patients to first go through days of withdrawal.  Naltrexone patients on the other hand can miss the morning’s naltrexone, and later that night relapse using mu receptors that are even hyper-sensitive to agonists.

As for arguments that patients on buprenorphine are impaired, I would love to see my attorney-patients take part in THAT debate.  Concerns of impairment have come from poorly designed studies where buprenorphine groups consisted of patients with no tolerance to the medication. I suspect that medical reporters too often read the abstract and skim the ‘materials and methods’—let alone the statistics!

If ‘success’ consists of moving to naltrexone—a medication that many real-world addicts reject–   how long is naltrexone continued, and what happens when it is stopped?  Do people go back to heroin again?  If not, why not? The cycle of ‘use, treat, cease treatment, use, and repeat’ should be a black box warning on naltrexone— as soon as they finish stamping the warning on the steps of every residential treatment center.

I’ve been accused of being too long-winded.  The short version for those who skipped to the bottom:  buprenorphine-based medications offer an effective, tolerable, long-term treatment for a chronic, life-long disorder.  How many people will die in their quest—or their doctor’s quest—for ‘abstinent recovery’ with or without naltrexone?  Emphasis on naltrexone is just one more example of looking the gift horse of buprenorphine treatment in the mouth.

Sigmon SC, Dunn KE, Saulsgiver K, Patrick ME, Badger GJ, Heil SH, et al. A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers. JAMA Psychiatry. Oct 23 2013;

A global surge in ADHD diagnosis has more to do with marketing than medicine

Sorry, guys…I’ve been busy working and on a couple of other projects.  I’ll be back in person tomorrow, with luck. In the meantime: Many websites promoting ADHD drugs offer checklists with questions like these: Do you fidget a lot? Is it hard for you to concentrate? Are you disorganized at work and home? Do you […]

LDT Battle Lines Drawn: FDA Announces Jan. 8-9 Public Meeting on LDT Framework; Lab and Medical Groups Send Letter to FDA Commissioner Urging Notice-and-Comment Rulemaking; FDA and Patient Groups Advocate for LDT Framework on Hill

By Jamie K. Wolszon -

A battle is brewing between proponents and opponents of FDA’s plans to actively regulate Laboratory-Developed Tests (LDTs), with several developments involving both camps in the past two weeks.  On the proponents’ side, on November 21, FDA announced that it will be holding a public hearing on January 8-9, 2015 at the National Institutes of Health (NIH) campus in Bethesda, Maryland.  That announcement came on the heels of a November 18 briefing on Capitol Hill by FDA, the Centers for Medicare & Medicaid Services (CMS) and patient groups advocating for the draft guidances (see our previous post here). 

Opponents of the draft guidances were similarly active during this time period.  Also on November 18, several laboratory and medical groups and laboratory directors sent FDA Commissioner Margaret A. Hamburg a letter arguing that if the agency proceeds with the framework, it must do so through notice-and-comment rulemaking.  That same day, one of the signatories of the letter, the American Clinical Laboratories Association (ACLA) announced that it had hired two very prominent litigators to help the association fight the draft guidances.  Although a new development will no doubt appear the moment after we post this blog, we detail the developments of the last two eventful weeks.

FDA announces January 8-9 public meeting at NIH campus in Bethesda.  FDA has outlined an agenda of topics for discussion at the public workshop.  According to FDA’s Federal Register notice, there will be six sessions on designated topics.  The six sessions will address the following: (1) components of a test and LDT labeling considerations; (2) clinical validity/intended use; (3) categories for continued enforcement discretion, including rare disorders; (4) notification and Adverse Event Reporting (MDRs); (5) public process for risk classification of tests and prioritization for enforcement of premarket review requirements; and (6) Quality System Regulation.  For each of the sessions, FDA provides questions in the Federal Register notice for which it seeks input during the meeting.

FDA states in the Federal Register notice that registrants wishing to present during a public comment session should identify which topics they wish to address.  FDA states that the agency “will do its best to accommodate requests to make public comment.”  Following the close of registration, “FDA will determine the amount of time allotted to each presenter and the approximate time each oral presentation is to begin, and will select and notify participants by December 17, 2014.”  It is unclear how FDA will select presenters.  It also is unclear whether a presenter could address multiple topics in different sessions, and whether presenters could make a general comment that they oppose the very concept of FDA regulation of LDTs.  Consistent with prior FDA statements, FDA is looking for feedback on its framework and not whether there should be FDA regulation of LDTs at all.  FDA also is soliciting electronic or written comments on all aspects of the public workshop by February 2, 2015. 

FDA, CMS and patient group briefing on the Hill.  The American Cancer Society Action Network, the American Heart Association, and the Ovarian Cancer National Alliance, in cooperation with Rep. Louise Slaughter (D-NY), hosted a November 18 briefing to advocate for the draft guidances, according to a press release.   Speakers at the briefing included Congresswoman Slaughter; Len Lichtenfeld, Deputy Chief Medical Officer for the American Cancer Society (Moderator); Elizabeth Mansfield, Deputy Director for Personalized Medicine, Office of In Vitro Diagnostics, FDA; Judith Yost, Director, Division of Laboratory Services, CMS; Richard Schilsky, Chief Medical Officer, American Society of Clinical Oncology; and Laura Koonz, Director of Policy, Ovarian Cancer National Alliance.  According to a Congressional Quarterly article reporting the event, “FDA’s reviews are for safety and effectiveness for the marketplace and are much more extensive types of reviews, because the [CMS] reviews for analytical validity are very narrow,” said Judith Yost, director of the laboratory services division for CMS. “The clinical validity is not approached [under CMS] at all.”

Laboratory, medical groups and laboratory directors send letter to FDA Commissioner stating that FDA must use notice-and-comment rulemaking, not guidance.  The November 18 letter states that “the draft guidance documents conflict with existing regulations and would impose substantial new requirements on clinical laboratories, hospitals, physicians, and other healthcare providers without complying with notice-and-comment rulemaking as required under the Administrative Procedure Act” (APA).  The letter was careful to preserve the legal argument that some of the signatories do not believe the agency has the statutory authority to regulate laboratories at all.  “The FDA’s statutory authority to regulate laboratory developed testing services and the scope of the proposed guidance remains a matter of significant legal controversy, and while a number of the undersigned organizations do not waive their legal claim that the FDA lacks the statutory authority to regulate laboratory developed testing services, to the extent that it is established that the FDA does have such authority, all of the undersigned are unanimous that the overwhelming weight of legal authority dictates that the proposed new requirements outlined in the draft guidance must be issued through notice and comment rulemaking.”

Signatories of the letter included, among others, the American Medical Association (AMA), ACLA, the American Hospital Association, the American Association for Clinical Chemistry, and some leading medical institutions. 

The argument that any FDA effort to actively regulate LDTs must go through notice-and-comment rulemaking is one that has repeatedly been presented to, and rejected by, FDA.  For instance, in 1992, HPM submitted a citizen petition that included the argument.  The Washington Legal Foundation’s Sept. 2006 and ACLA June 2013 citizen petition also included the argument.  FDA denied all of those citizen petitions. 

ACLA announces that it has engaged prominent litigators to help oppose FDA effort.  On November 18, ACLA announced that it had retained Paul D. Clement and Laurence H. Tribe, two distinguished constitutional and APA litigators, to help the organization oppose the framework.  “ACLA’s decision to hire Messrs. Clement and Tribe, and their decision to take this case, should be seen as an indication of the strength of our conviction that the merits favor protecting patients, labs, and physicians from this unjustified regulatory action,” the press release states.  Retaining these two litigators can be viewed as a shot across FDA’s bow.

Undoubtedly, there will be more developments as different groups seek to bolster their position on whether FDA should regulate LDTs, and if so, how.

Court Dismisses Lawsuit Alleging Unreasonable Delay in FDA’s Lack of Response to Seafood Advisory Citizen Petition

By Ricardo Carvajal

The D.C. District Court granted FDA’s motion for summary judgment in a lawsuit alleging unreasonable delay in the agency’s response to a citizen petition asking for the inclusion of FDA/EPA’s seafood consumption advisory in seafood labeling and at point-of-sale.  Although the petition was filed in July 2011, the court found that “FDA’s delay in responding to Plaintiffs was not so egregious as to warrant intervention at this time.”  The court based its finding on a number of factors, including:

  • The complexity of the scientific and technical issues involved, including ascertaining the risks of mercury on childhood development in light of the net effects of seafood consumption, as well as ascertaining the pros and cons of placing mercury warnings at point-of-sale;
  • The fact that the agency is updating the advisory language of which the citizen petition seeks to compel expanded use;
  • The absence of “certain danger” associated with the delay in FDA’s response to the citizen petition; and
  • The need for FDA to have flexibility in allocating resources to address issues related to mercury consumption, as well as other priorities.

The court noted that its “calculus may change” once FDA/EPA finalize their update to the advisory, after which “further delay could become unreasonable.”  The court therefore urged FDA “to act with alacrity” once that task is completed. 

The draft updated advisory and corresponding Q&As are available here, as is a link to submit comments.