Naked Medicine

By Dan Abshear

Terminal patients are those who are not expected to live due to usually illness such as advanced prostate cancer (cT3). If the patient has 6 months or less to live, those patients are considered terminally ill. Regardless, if a patient is terminal, they are without a cure or tolerable treatment for their illness. Since such patients will likely die in a short period of time, treatment options, even if unproven, are often desired by such patients. This is understandable, because at such a severe stage of illness, such as prostate cancer, possible extension of their lives with comfort is worth it to them, regardless of lack of evidence of proof of whatever treatment that may be advantageous to them regarding these issues. The FDA, however, claims authority on the treatment options of such patients, although that administration has proven itself over the years to be rather inadequate with its frequent drug recalls and black box warnings, and they do these things only under pressure from the public, usually.

Prostate cancer is a rather frequent occurrence- with between 10 to 20 percent of men predicted to acquire the disease during their lifespan, resulting in about 30,000 deaths a year from this disease of the one million men who have prostate cancer in the United States. Furthermore, there are different stages of prostate cancer, and the more severe the prostate cancer cases are which is determined by such methods as bone scans and Gleason’s scores, which is a score that assesses prostate tissue after it is biopsied and if it is determined that the stage of cancer is severe by this and to estimate proper treatment options if proven to be malignant. Typically, the initial suspicion of prostate cancer is determined by the results of what is called a PSA (Prostate Specific Antigen) blood test, as PSA is a protein produced by prostate cancer cells. If the PSA blood test is above normal limits, a prostate biopsy is performed to determine and confirm not only the presence of cancer, but also the severity of the disease on such a patient.

Yet fortunately, and as you will read, innovation still exists in medicine. A few years ago, a small Biotechnology company called Dendreon was working on a conceptually new treatment for the worst prostate cancer patients, and this treatment therapy created by Dendreon was named Provenge. Provenge is the first immunotherapy biologic treatment for the progressed prostate cancer patients, and has proven to be a very novel and innovative treatment option for advanced prostate cancer patients who are terminally ill. Usually, these patients are unresponsive to usual treatment methods for prostate cancer, and are left with chemotherapy as their only treatment option at such a traumatic stage of prostate cancer. Understandably, most patients at this stage refuse treatment entirely, largely due to the brutal side effects of such chemotherapy treatments as Taxotere (Sanofi Aventis, docetaxel). The immunotherapy method developed by Dendreon required the removal of white blood cells of the diseased patient and, after altered, are re-injected into this patient now designed to attack what is called PAP, which is on prostate cancer cells only. This treatment required only three such injections in a period of six weeks. This resulted in life extension twice that of chemotherapy treated prostate cancer patients of this severity, and without the concerning side effects of chemotherapy. The medical community and survivors of prostate cancer were elated and waited with great anticipation for access to this treatment method.

Fortunately, as the years passed, Provenge, by 2007, had convinced others of its safety and efficacy in its benefit for severe prostate cancer patients. This caused great joy to such patients and their families. Perhaps greater elation was experienced by the caregivers and specialists of such a disease, such as urologists and oncologists who treat such patients. While Provenge was on fast track status at this time at the FDA, the FDA panel thankfully recommended with clarity the approval of Provenge based on its proven and substantial efficacy and safety demonstrated in its performance in past trials. The FDA announced this to the public in the early Spring of 2007, I believe.

Now for the bad news: With great shock and surprise, the FDA agency rejected the approval of this great treatment for very sick patients due to, they said, ‘lack of data’ in May of 2007. This contradicts their favorable opinion of Provenge weeks before delivering this terrible news. Especially when one considers the FDA Commissioner is a prostate cancer survival himself!

Soon after this judgment was passed by the FDA, conflicts of interest were discovered by others. For example, a member of the FDA agency who was evaluating Provenge, Dr. Scher, was found to have a financial commitment to a future competitor of Provenge that was being produced by a company called Novacea, and this company had signed a co-promotion agreement with Schering with this similar prostate cancer drug being developed by this company. Dr. Scher never disclosed this conflict during the approval process of Provenge. As it turns out, this anticipated prostate cancer drug made by Novacea was discovered to have serious flaws, and Schering pulled out of the agreement with Novacea. In addition to this incident and before May of 2007, baseless letters were anonymously delivered to the FDA stating negative qualities about Provenge that were without merit and speculative claims about the treatment. Yet overall, the disapproval by the FDA of Provenge angered many, and a newly formed advocacy group called Care to Live filed a lawsuit against the FDA for their clear lack of protocol or knowledge about such complex treatment agents as Provenge at the end of last year.

Terminal patients, I surmise, desire comfort during their progressive disease that has placed them in the last chapter of their lives, and certainly should have a right to choose any treatment that possibly could benefit them. At this stage of such a patient, one could argue, safety of any treatment option is not of concern to these patients, because they are going to die anyway. Yet the FDA, with reckless disregard and overt harshness for these very ill patients, ultimately harmed others more by not approving Provenge with deliberate intent.

The FDA does in fact presently have the ability to grant what is called conditional approval for such treatment methods as Provenge, and why they have not expanded this approval process to all terminally ill patients remains completely unknown. What is known is that they are harming those they pledged to protect so long ago by depriving such patients in need of treatment, as no other options are viable presently that are as safe and effective with great tolerability associated with Provenge. So now the FDA appears to be a bought, corrupt, and incompetent administration without loyalty and dedication to the public and its health. This needs to be corrected in any way possible for the lives of others. A terminally ill patient has a personal right to obtain and access such treatments upon their own volition as well as the discretion of their doctor, just as a terminally ill patient is granted an individual right to die, if they choose to do so. It is an individual decision in such cases that should be void of interference from others.

“Facts do not cease to exist because they are ignored.” — Aldous Huxley

By Sally Satel, M.D.

On the front page of the Washington Post last week was a headline geared to spark the ire of those who have a congenital animus toward pharmaceutical companies–”Comparison of Schizophrenia Drugs Often Favors Firm Funding Study“.

The Post article noted that, according to a recent study, nine out of ten head-to-head company-funded clinical trials of antipsychotic medications were found to favor the drug whose maker funded the study.

The study, published in the February issue of the American Journal of Psychiatry by German and American psychiatrists, reviewed 30 drug trials of second-generation antipsychotics, also called atypicals, published between 1966 and 2004. Five drug companies were responsible for underwriting these 30 trials.

Aside from its headline, the Post article was well done and revealed important lessons from the study. For instance:

1. From a clinical standpoint today, it doesn’t matter much which drug wins a horse race.
2. The company studies provide useful information, not pabulum.
3. Most important, we need more research.

Let’s look at these points one by one.

In the real world of practice trial results are less important than you think. In modern psychiatry, there are no first-line drugs. Years ago, by contrast, lithium was the pharmaceutical of choice for maintenance treatment of the manic symptoms of bipolar illness. Today, the FDA has approved several mood–stabilizers (anticonvulsants) for treatment and suppression of mania, not to mention off–label drugs.[1] Take posttraumatic stress disorder. Today, only two SSRI–type drugs are FDA approved for PTSD but they are not dazzlingly effective. In fact, because the condition varies so much from patient to patient, other medications that are not approved for the condition (e.g., low-dose antipsychotics, anticonvulsants and benzodiazepines) can be very helpful in certain individuals.

Why do doctors struggle so much to find effective treatments? The state of the art in prescribing effective antipsychotic drugs is still pretty poor and, as a result, doctors are often forced to take a trial and error approach. When starting a depressed patient on an antidepressant or an antipsychotic, doctors typically choose the drug they are most skilled in using. This is a perfectly reasonable choice, given our rather slim knowledge about how to tailor medications for each patient.

The largest and most recent government–funded studies tend to be enormously humbling for physicians and companies alike. Data from the new STAR*D Study (Sequenced Treatment Alternatives to Relieve Depression) show that only 25-33% of subjects achieved full remission with antidepressants.[2] (Granted, a higher percentage of patients had partial relief, and sometimes that is enough to improve daily functioning significantly. Still, higher rates of full-remission are surely desirable.)

Another study, CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness Study) found that three-fourths of all subjects asked to stop their antipsychotic, either because it was not helping or because side-effects were unacceptable to them.[3] The CATIE study lasted an unprecedented duration (18 months) and enrolled an unprecedented number of subjects (nearly 1500), thus permitting a fuller picture than most other clinical trials.[4]

For the record, psychiatrists do have some guideposts in selecting drugs. In my own practice, I rely on four rules of thumb for using (or avoiding) a specific drug. I use a particular treatment (1) if the patient had a good response to it during a prior treatment episode, and (2) if a close relative benefited from that drug (aka: the pharmacogenetic rationale).

I avoid treatments if (1) the patient says he would find a side-effect totally unacceptable, such as weight gain. If the medication poses a sizeable risk of causing a medical complication, such as worsening hypotension, diabetes or high cholesterol, I still might use it but watch the patient very carefully. I also avoid treatments if (2) a drug is very expensive–and the patient has to pay out of pocket. In that case, I use a first generation, generic antipsychotic and follow for signs of tardive dyskinesia, a movement disorder that can emerge with long-term use.

Company funded studies still provide useful information. It is no mystery (or conspiracy) why studies comparing the same drug can come out differently. In short, they are conducted using different designs, different statistical tests, and/or different outcome measures. Anyone can read the published studies and see for themselves how they differ. There is transparency here, but the psychiatrist must take time to read the entire study, not just the abstract.

Some factors that can favor one or another drug are: the doses used (e.g., a low-dose of a clearly superior drug will make it seem lame when compared to a standard dose of an inferior one), the duration of the study (i.e., trials may be only four weeks long but different drugs may have different times to maximum effectiveness), and outcome measures (i.e., reduction of psychosis but not behavioral withdrawal, or vice-versa).

One can be forgiven for wondering whether some trials have been conveniently engineered to make the sponsor look better–for example, when a low dose of a competitor’s drug is used or when the researcher doesn’t seem to look too hard for side effects or doesn’t report all of them. On the other hand, often researchers truly don’t know to look for a novel side effect or do not know what the optimal duration of study should be. Why? Because we need to know more!

We need more research. This is the main conclusion physicians, patients, and the media should take away from February’s American Journal of Psychiatry study. The main limitation of so many clinical trails is that the data they yield don’t help the clinician with a specific patient. The kinds of information psychiatrists need are how to home in on a medication that will be best for a particular patient. Switching around medications and dealing with bad side-effects take large tolls on patients. Not only do they cause suffering or vast inconvenience, these adverse events problems can cause poor compliance or outright refusal to try any other drug. It is demoralizing to a patient to continue to be sick and to go from one drug to the next; he starts to fear he will never get better. And, of course, it is a problem, though a routine one, for the physician.

Legitimate concerns about clinical trials abound. For instance, how do the findings of clinical trials compare to patients that physicians see everyday (who are, generally speaking, more likely to have other mental and physical problems)? Clinical trials typically enroll subjects who have classic symptom constellations and are medically relatively healthy. As well, such subjects are able to give informed consent; very psychotic patients often cannot. Also, do differences in drugs justify differences in cost and how do those differences vary across patient subtypes? And, of vast importance, what drugs really help the patient get better, not in just alleviating symptoms, but in terms of day-to-day functioning?

Pharmaceutical companies may not be interested in these questions. Either the National Institutes of Health or some other government or non-profit entity could conduct these trials. Currently, only NIH can sponsor studies large enough to involve a sufficiently large number of patients that the results yield more clinically-relevant information. That’s a major weakness of company-sponsored trials, no matter how well done. An additional virtue of non-industry funding is that the specter of conflict of interest is erased.[5]

Schizophrenia is one of the most mysterious and vexing diseases in psychiatry. The most afflicted often give up their lives to it. They are desolately lonely and tormented by hallucinations and paranoia. Neuroscientists have made tangible progress but the etiology or etiologies of the disease (the most popular theory is that gene mutations lead to abnormal development of neural circuits, particularly in the context of external stress, but a number of respected researchers have even suggested a viral cause) remain murky. This makes it difficult for physiology to inform drug development.

There is no question that some patients have Lazarus-like recoveries when the right medication is found. The search, though, can be a time-consuming pharmaceutical odyssey. Worse, however, is that not enough patients get excellent results. Clearly, we need more evidence about the medications we have now and even better drugs in the future.

We shouldn’t become cynical about the companies pursuing these cures. Competition between competing therapies broadens our understanding of mental illness and can help researchers chart a course towards the next generation of treatments. In a sea of uncertainty, that’s the best we can hope for.

Dr. Sally Satel is a resident scholar at AEI.

Notes
[1] Some psychiatrists consider clozapine (now off patent) to be a first line drug for schizophrenia. It has been clearly demonstrated to be superior to other atypical antipsychotics but is not very popular because of the necessary blood monitoring. Also, because it is generic, there is no pharmaceutical advertising behind it. See Tamminga, C. Practical Treatment Information for Schizophrenia American Journal of Psychiatry 163:563-565, 2006. Of interest, now lithium is making a comeback. A number of new studies have shown that it has a significant suicide-prevention effect, see Tondo L., Hennen J., Baldessarini R.J Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatrica Scandinavica, vol. 104, Number 3, September 2001, pp. 163-172(10); Cipriani A, Pretty H, Hawton K, Geddes JR. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry. 2005 Oct;162(10):1805-19; Kessing LV, Sondergard L, Kvist K, Andersen PK. Suicide risk in patients treated with lithium. Arch Gen Psychiatry. 2005 Aug;62(8):860-6;Muller-Oerlinghausen B, Felber W, Berghofer A, Lauterbach E, Ahrens B.The impact of lithium long-term medication on suicidal behavior and mortality of bipolar patients. Arch Suicide Res. 2005;9(3):307-19.

[2] Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1305-7;Rubinow DR Treatment strategies after SSRI failure–good news and bad news. N Engl J Med. 2006 Mar 23;354(12):1305-7.

[3] Lieberman JA, Stroup TS, McEvoy JP, et. al. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.N Engl J Med. 2005 Sep 22;353(12):1209-23.

[4] And, still, patients on first generation, or typical, antipsychotics were not followed long enough to track emergence of tardive dyskinesia, the major aversive side-effect from long term use.

[5] Other suggestions: perhaps the FDA could require a new medication be included in at least one large, long-term trial funded by the company and designed and conducted by an independent group at the expense of that company or jointly supported by NIH. Alternatively, one could have the FDA require that as part of Phase IV (post-FDA approval) that companies would be obligated to contribute to CATIE-like studies to see how effective medications are when used they way clinicians use them for the patients that they treat. Since these would be head-to-head studies, several companies would contribute and this would combat any bias that could be alleged when a single company pays.

By Deborah Serani, Psy.D.

It is a difficult, yet brave and courageous moment when someone makes the decision to pursue mental health therapy. But more difficult than the decision to go to therapy is the decision of who to go to for therapy.

So, how does someone find a good therapist?

Types of Therapists
First, it is important to think about the type of therapist you think is best for your presenting symptoms and issues. There are many kinds of mental health therapists, but sometimes understanding “who does what” can be confusing. Here is a list to help identify the specialties and degrees therapists can hold.

Psychologists
In the United States, Doctors of Philosophy (Ph.D.), Doctors of Psychology (Psy.D.), or Doctors of Education (Ed.D.) must complete at least four years of post graduate school, however, only those who have been licensed can call themselves Psychologists. Licensed practicing psychologists are specifically trained in the mind and behavior as well as diagnosis, assessment and treatment of mental, emotional, and behavioral disorders. The treatment provided is “talk therapy”. It is important to know that not all psychologists are experienced therapists. Some specialize in areas such as statistical research or industrial psychology, and may have little experience treating people. Therefore, it is important to inquire about the caliber of clinical experiences. Psychologists do not prescribe medication.

Social Workers
Clinical Social Workers (C.S.W.) usually have earned at least a Masters’ Degree, which is two years of graduate school, and some Social Workers obtain a doctoral degree (D.S.W.) . Clinical Social Workers credentials may vary by state, but these are the most common: B.S.W. (Bachelor’s of Social Work), M.S.W. (Master’s of Social Work), A.C.S.W. (Academy of Certified Social Workers), or D.C.S.W. (Diplomate of Clinical Social Work). Although there are exceptions, most licensed clinical social workers generally have an “L” in front of their degree (L.C.S.W.) communicating that they are a Licensed Clinical Social Worker. Clinical Social Workers also receive training in the prevention, diagnosis, and treatment of mental, behavioral, and emotional disorders. Their goal is to enhance and maintain physical, psychological, and social functioning in who they treat.

Psychiatrists
A Psychiatrist completes a medical degree (M.D.) like any other physician, followed by a four-year psychiatry specialty. Psychiatrists prescribe medication yet sometimes do psychotherapy with patients. Psychiatrists, unlike Psychologists, have the background and experience to understand how the body and the mind as a whole react when psychiatric medication is given, and have extensively studied the total body including brain biochemistry, tissues, glands, and organs, leading to a fundamental understanding of how these all interact and react to the patient’s environment in mental health and mental illness.

Marriage Family Therapists & Professional Counselors
Licensed Marriage and Family Therapists (L.M.F.T.), and Professional Counselors (L.P.C.) usually have two years of graduate school and have earned at least a Masters’ Degree such as: M.A. (Master of Arts), M.S. (Master of Science) or M.Ed. (Master of Education). Marriage and Family Therapists have additional specialized training in the area of family therapy.

Certified Counselors
Certified Counselors are typically trained in drug or alcohol abuse specialties. A Certified Addiction Counselor (C.A.C.) or a Certified Alcohol Counselor, (C.A.C.) may have a I, II, or III added to their degree signifying the level of training in counseling (CAC-I, for example). A C.A.C. Counselor may or may not have a master’s degree. Counselors are trained for supportive therapy. C.A.C’s work within the field of alcoholism and substance abuse, providing education, consultation, counseling, aftercare, recovery and advocacy.

Religious/Theology/Pastoral Counselors
These are counselors who are clergy, pastors or who have a Master of Divinity (M.Div.) degree, or a Doctorate in Theology (Th.D.) from a seminary or rabbinical school, with additional training in therapy. These spiritual counselors are trained in both psychology and theology and thus can address psychological, religious and spiritual issues.

Counseling Nurses
Psychiatric Nurses and Nurse Practitioners comprise a growing segment of mental health treatment professionals. They display the credentials R.N. (Registered Nurse), R.N.P. (Registered Nurse Practitioner) or M.S.N. (Masters of Science in Nursing). A Psychiatric Nurse is a registered nurse with a master’s degree who has been trained in individual, group, and/or family psychotherapy. The Psychiatric Nurse and the Nurse Practitioner view individuals from a holistic perspective, taking into account both physical and mental health needs while focusing on human behavior.

Word of Mouth To Yellow Pages
Now that you know the kind of therapists with which you wish to work, how do you choose one?Here are a few ways that can provide leads to a good therapist.

Word of mouth: Asking a friend or relative that you trust can be a great way of finding a reliable therapist. When a clinician is highly regarded, there is usually a buzz in the community about him or her.

Professional Referrals: Contacting your general physician, or inquiring with school guidance and special service staff if you are looking for someone to work with your child are good ideas. Contacting local psychological, psychiatric or counseling organizations can be very helpful in pointing you in a direction as well.

Insurance Company: If you have an insurance company, another suggestion is to call them directly and ask them to give you a few names of therapists in your area, and ones that specialize in the disorders or issues with which you are experiencing.

Church or Temple: Many churches and temples have outreach programs where the person in charge can help you find a therapist.

Yellow Pages: Many times I get calls from people who look me up in the Yellow Pages. With nowhere else to turn, people cold-call with the hopes of finding a good therapist. This experience can be frustrating and may lead you down a bumpy road of contacting therapists who do not specialize in what you need. If possible, try one of the other strategies listed above to help you find a good therapist.

The Initial Phone Call
Once you have a few names, find the time to call each one and talk on the phone with him or her. You can get a great feel for a professional during this informal chat. If you make a connection on the phone, arrange for an appointment to consult with the therapist. I call this “the meet and greet” consult where I get to meet the potential patient, assess the symptoms and issues and make sure that my training and expertise are appropriate for the necessary treatment. This is a time where the potential patient gets to know me as well, how I will work and also learns about my approach to treatment and the parameters of therapy. Though comfort and connection are necessary factors, so too are making sure that the therapist of your choice is educated, seasoned and a specialist in what you are seeking.

Questions to Ask:Most therapists will welcome the opportunity to answer any questions that you may have. Here are some of the most important ones to consider:

1. What is your professional training and degree?

2. How much specialized training and experience have you had with what I am seeking help for?

3. What theoretical school of thought do you follow?

4. How long are the sessions?

5. What is the cost of each session?

5. How does insurance work with mental health therapy?

6. What is your policy on cancelled appointments?

7. Have you been in therapy yourself? If so, how long?

8. Is it possible to reach you after hours in the event of an emergency or crisis? If so, how?

9. Do you receive regular supervision on your cases or belong to a peer supervision group?

10. What professional organizations do you belong to?

Good Therapy
Once these bases are all covered, and you settle into treatment, you should slowly begin to feel an expansion within yourself. Your awareness will widen, your feelings may swell, and you may find yourself thinking in new ways about your situations and experiences in life. Therapy may be tough on occasions, but in time, you should start learning techniques to help change, shift or remedy symptoms. That is how the arc of good therapy progresses. Last, but not least, always, ALWAYS, be sure that the professional you choose to work with is a licensed mental health practitioner

Regarding, “Device Companies Post How Much They Paid Orthopedic Surgeons” today’s Health Blog revealed that the millions of dollars paid to orthopedic surgeons are mostly in the form of royalty payments (74% of total payouts), at least, for Zimmer:

Zimmer’s CFO broke down his company’s payments during a talk today at a Piper Jaffray health-care conference. According to a slide in the CFO’s presentation, 74% of the outlays were for royalties, 11% for consulting, 10% for “research & clinical” work, 4% for “education & other” and 1% for travel and expenses, Dow Jones reports.

Source: Health Blog

If the docs did indeed own the intellectual property that device companies are licensing to use, then royalty payments make perfect sense. Still, from the blog comments, some remain skeptical of the rationale behind such high payouts.

Doctors can now fax Senator Chuck Grassley at 202-228-2131 to report on drug companies that the doctors perceive to “push too far” and are being “bullied” by drug companies. Doctors can remain anonymous and send information by mail or fax. This effort came at the heels of the Avandia investigation earlier this year, where manufacturer GlaxoSmithKline was accused of pressuring Avandia critic John Buse to change his story about Avandia risks. The company said it wanted Buse to correct factual errors Buse made about the drug, while Buse said the company used intimidation tactics.

I wonder if Grassley knows what floodgate he’s opening up by creating a service that allows anonymous tips on what is very much a subjective behavior (i.e. what one perceives to be intimidation or bullying or “hardball tactics”), and whether the senator is actually equipped to conduct investigations into every complaint filed. Source: WSJ Blog.