Lab Soft News

Disease Mongering (i.e., Medicalization) by Pharmaceutical Companies

The etymology for the word monger is quite interesting -- it was not originally used in a pejorative sense, as it is today, but referred neutrally to a trader or middleman. Mongering today is used to refer to an activity such as the peddling of cheap or illicit goods. A recent article discussed the medicalization of newly recognized and previously untreated problems and referred to the process as disease mongering (see: Disease Mongering or Medicalization). Below is an excerpt from it with boldface emphasis mine:

The overlap between business ethics and medical ethics represent a moral minefield. Nowhere more so than in the domain of newly recognised and previously untreated disorders, syndromes and diseases, among them social anxiety disorder, non-physiological erectile dysfunction, aging, fibromyalgia, adult attention deficit hyperactivity disorder (ADHD), restless leg syndrome and female sexual dysfunction....Diagnoses can be very real and finding effective treatments certainly worthwhile, but it is the interests of patients that should be served and not purely those of pharma industry shareholders when a condition is medicalized. Some observers have suggested that the process of medicalization, in which issues and problems have migrated into the scientific realm coincides with the demise of traditional values....It’s worth repeating, pharma companies enjoy increased profits because of medicalization, but that does not mean that we should not be treating previously latent disorders. Quality of life might be improved for countless individuals with new treatments....After all, your particular take on the human condition may one day be recognised as a disorder by the medical profession, but it remains your choice as to whether take the medicine.

One of the least desirable aspects of the web is that it often makes it difficult for some readers to distinguish between good advice and bad advice in the medical domain. This is in contrast to, say, a printed book where the author and the publisher are known and will stand behind the content. Some medical web sites such as MayoClinic.com do provide such a guarantee.

Broadcast media such as television can also fool naive viewers about medical matters. Unfortunately, advertisers have been refining their powers of persuasion with this communication channel for more than 50 years. I cringe every time I see direct-to-consumer advertisements from pharmaceutical companies on television. My discomfort is particularly acute for diseases where the etiology of the disease is not established like fibromyalgia but drug cures are being offered. I frequently ask myself the following question: how can a disease be treated when its etiology has not been established?

Although the web can also be a minefield of misinformation, this bothers me less than television which operates in a one-to-many broadcast mode and does not allow for interactivity or search to sort out valid information from misinformation. For example, a search using Google for "fibromyalgia" and "cause" or "etiology" yielded 1,870,000 hits. I am sure that there is a pony somewhere in this mass of information. The key to this problem of accurately searching on the the web is the need for a trusted source for medical information such as Mayo Clinic. There are many of them but also a lot of noise in the system.

Relationship of Pharmaceutical Companies to Continuing Medical Education

KevinMD, the author of a very successful health blog, posted a recent note posing the controversial question of whether the fact that pharmaceutical companies are now generally banned from providing gifts to physicians is hurting the economy (see: How banning pharmaceutical gifts to doctors may hurt the economy). Below is his note in its entirely with boldface emphasis mine:

Massachusetts is considering implementing some of the toughest laws in the country regulating the pharmaceutical industry from giving gifts of any kind to doctors, and restricting drug company funding. MedPage Today ...reports that one unexpected consequence is that many major physician conferences are pulling out of the city. For instance, the American Academy of Allergy, Asthma & Immunology pulled its 2015 convention out of Boston, citing difficulty finding "sponsorships and to provide education courses under current legal conditions." Millions of dollars will be lost, both in convention revenue and hotel bookings. There's talk that other major physician conferences are bypassing Boston altogether. Will the unintended consequence of hurting the state economy force the government to loosen up their oversight of pharmaceutical gift-giving?

I feel compelled to weigh in on this topic as I have in a previous note because I have participated in, and managed, CME conferences for many years (see: On the Corrosive Influence of Big Pharma on Academic Physicians). Most medical conferences require some monetary support from vendors to succeed. Otherwise, the registration fees would be so high that few physicians would probably attend. However, the participation of vendors such as Big Pharma should be viewed as an opportunity and not a problem. Physicians, like all professionals, need to update their skills constantly and this goal can be achieved, in part, at medical conferences. They can learn much from the conference faculty who are selected on the basis of their expertise and teaching skills. Such faculty members must not be obligated in any way to the sponsoring pharmaceutical companies. Conference registrants can also acquire information from the pharmaceutical company representatives who work the vendor displays that are browsed by conference registrants. A "fire wall" must be placed between the didactic content provided by the faculty and the sales efforts of the vendor representatives. In my experience, such a barrier is not that difficult to erect. The lecture area must be a "no spin" zone.

It strikes me as childish and precipitous for the American Academy of Allergy, Asthma and Immunology to pull a conference that will occur six years in the future for lack of [pharmaceutical] sponsorship. There is a political agenda at work here. I recommend that everyone concerned take some deep breaths. A new modus operandi needs to be developed between the pharmaceutical companies and the professional societies pertaining to the structure, organization, and funding of conferences along the lines described above. This probably won't happen overnight. However, the fact remains that physicians need to attend conferences and the company representatives need an opportunity to interact with them. These interactions may not be as frequent in the physician office settings because of the high cost of such calls. My guess is that medical conferences will continue but with new rules, even in Massachusetts.

Big Pharma's Evolving Research Collaboration with Medical Schools

I have posted a number of previous notes about the growth of contract research organizations (CROs) fueled, in part, by the willingness of Big Pharma to outsource various components of drug discovery and the management of clinical trials to these companies. Big Pharma continues to slim down because of poor earnings and drug pipeline problems. The latest news is that Pfizer is cutting 800 research positions and part of its sales force (see: Pfizer to Cut Researchers as It Hones Its Focus; Pfizer May Cut Sales Force by Nearly a Third). You don't need to be a genius to figure out where the pharmaceutical companies will look for research talent in addition to that provided by the CROs. A recent article spells this new trend out clearly (see: J&J, Vanderbilt ink rich partnering deal). Below is an excerpt from the article with boldface emphasis mine:

Johnson & Johnson is teaming up with Tennessee's Vanderbilt University to discover and develop new schizophrenia treatments. The extensive relationship calls for Vanderbilt to receive $10 million over three years and up to $100 million in milestone payments. In an unusual twist, Vanderbilt researchers won't just discover the drug; they'll continue to work out kinks in the compound until it's ready for human testing. This is unusual because the "drug optimization" process is usually conducted by the biopharma company rather than the university. This deal represents Big Pharma's new deal with academia. Pharma and biotech companies have developed closer ties with labs that are doing the earliest research, even having their scientists interact with university researchers on a regular basis. Previously, the industry simply gave university research labs funding and, in return, reaped the rights to whatever discoveries came out of those labs. Supporters say this set-up benefits both sides and gets groundbreaking research into the clinic quickly. Critics worry that universities are becoming too dependent on the industry for research funding.

Obviously, medical schools have their own culture that is quite distinct from that of the pharmaceutical industry. One of the most important of these is the academic interest in basic research as opposed to the applied research favored by the pharmaceutical industry. As the relationship between Big Pharma and academe expands, there will surely be misunderstandings on both sides. Of course, many academic institutions are experiencing current budget shortfalls and restrictions on NIH funding, so they will be unusually receptive at this time to other sources of research funding.

As readers of this blog will understand, a key component of pharmaceutical research is clinical laboratory testing with recent special emphasis recently on biomarkers. I don't know to what extent the Johnson and Johnson contract with Vanderbilt spells out the extent of such support from the pathology and lab medicine units at Venderbilt. Recall that one of the major CROs, Covance, has special expertise in lab testing and has boasted in the past of having the world's largest central laboratory network (see: A Look at the World's Largest Central Laboratory Network). If the relationship between the pharmaceutical industry and medical schools continues to evolve, the pathology departments at these schools will inexorably be drawn into the process, both in terms of bench research expertise and clinical laboratory support.

Quintiles AcquiresTargeted Molecular Diagnostics to Provide Molecular Biomarker Services

I have posted a number of notes about contract research organizations (CROs), notably Covance and Charles River. My interest in these companies stems from my belief that their pursuit of new companies and technologies can be instructive and serve as a model for hospital-based clinical laboratories (see: Charles River Acquires Molecular Imaging Company). Continuing in this same vein, I read with interest that Quintiles Transnational has just acquired Targeted Molecular Diagnostics (see: Quintiles Acquires Targeted Molecular Diagnostics), Below is an excerpt from the press release with boldface emphasis mine:

Quintiles Transnational Corp. today announced that it has acquired Targeted Molecular Diagnostics (TMD)....The addition of TMD to Quintiles' Global Central Laboratories strengthens Quintiles' service offerings in oncology, an increasingly important growth area of drug development. It provides strong capabilities in tissue-based testing, a critical component of the modern oncology drug development process....TMD's biomarker technology will help Quintiles' customers better understand how their drugs work and in which populations they're most likely to perform best....TMD provides guidance through biomarker expression analysis and supports the development of numerous targeted therapies in oncology. The company works with customers in the design of effective clinical trials that reduce the time and cost of bringing new compounds to market. TMD currently supports clinical trials for pharmaceutical and biotech companies in over 40 countries and offers over 100 biomarker assays.

I have posted previous notes about the need to more closely align anatomic and surgical pathology with clinical pathology (see: Integration of Anatomic and Clinical Pathology; Reinventing Pathology: The Hematopathologist as a Model for the Pathologist of the Future; In-Vitro Biomarkers vs. In-Situ Biomarkers). Molecular diagnostics as applied to both bench research and clinical practice is being revolutionized by the measurement of new serum biomarkers, particularly for the diagnosis of cancer. Similarly, tissue analysis for drug research and surgical pathology is being greatly enhanced by the qualitative and quantitative assessment of these same biomarkers in tissue.

I have pointed out in a recent note how the boundaries between pre-clinical and clinical laboratory investigation are beginning to blur based on the increasing overlap between LIMSs and the LISs (see: LIS vs. LIMS: It's Time to Blend the Two Types of Lab Information Systems). I am wondering if some of the future plans of the Quintiles' Global Central Laboratories and other CRO-based research laboratories may lead them to compete in the future with the esoteric clinical reference labs in the areas of oncology molecular diagnostics and tissue imaging.

Medical Students Rally for Greater Disclosure of Faculty/Pharma Financial Ties

In general, I believe that medical students should spend their time hitting the books rather than engaging in various forms of social protest. However, I have just discovered a situation where it seems to be that a medical student "action" would be warranted (see: Harvard Med Students Might Want to Look Up Charles Grassley). Below is an excerpt from the note from the WSJ Health Blog:

Medical students, unite! It’s time to fight for your right to know your profs’ drug-industry ties! That’s what’s happening over at Harvard, where some 40 students rallied recently on the steps of Harvard Medical School’s Gordon Hall. Along with some folks from Tufts and Boston University, they were waving signs and pushing for tighter conflict-of-interest policies vis-a-vis Harvard docs and pharmaceutical companies....As the [Harvard] Crimson tells it, students have been trying for six years to get the administration to tighten its conflicts policies, both in the classroom and at the affiliated hospitals where the students train.  One idea they’re pushing is to require faculty and students, while talking about drugs in the classroom, to disclose any ties to the makers of those drugs. Harvard’s dean for faculty and research integrity, Gretchen Brodnicki [said that] the administration is taking the students’ concerns seriously. But she noted some practical issues, especially when it comes to the hospitals, which Harvard does not own or operate. The school can’t “force” affiliated hospitals to change their existing policies to line up with what the medical school requires internally, she said. She added, though, that the hospitals’ policies “go well beyond where we stop.”

I have covered in previous notes the problem of non- or inadequate disclosure of payments from Big Pharma on the part of medical school faculty (see: Medical Schools Share Some Blame in Scandals Involving Pharma Payments to Faculty; On the Corrosive Influence of Big Pharma on Academic Physicians). Clearly the faculty self-reporting system to medical school deans is not working, at least for some schools. As I noted in my note cited above, the medical schools need to share some of the blame. Here's my specific language:

...I don't think that the medical schools should emerge from these scandals untarnished. How is it possible for major medical schools to be "incapable of policing their faculty’s conflicts of interest." I can assure you that these institutions each employ hundreds of personnel in their research administration divisions to manage and audit research grants and contracts to the penny. And the reason for such diligence is obvious -- not to do so puts their research enterprise into jeopardy and such funding is the major sources of revenue for them.

The quote above from Harvard Medical School Dean Gretchen Brodnicki about the hands of school administration being tied regarding teaching hospital policies is a total "cop-out" and gives me little cause for optimism. The fact that Harvard Medical School does not "own" its teaching hospitals should not act in any way as a barrier for the harmonization of faculty ethical and conflict of interest policies across the various affiliated institutions.

Few Good Treatment Options for Pre-Diabetes and Metabolic Syndrome

I have written a number of previous notes about prediabetes as a component of the metabolic syndrome. The two constitute an enormous public health challenge globally. There are few treatment options for either condition other than weight loss (see: Research Study Documents that Obesity Cause Heart Inflammation). In Japan, the government is requiring that its people reduce their waist sizes, leaving enforcement to the large corporations that employ many of them (see: Japan, Seeking Trim Waists, Measures Millions). On July 23, 2008, the American College of Endocrinology released a consensus statement on the diagnosis and management of prediabetes. Below is an excerpt from an article that discusses this consensus statement with boldface emphasis mine (see: Consensus statement on prediabetes confirms proper management):

Approximately 57 million people in the United States have prediabetes, defined as either impaired fasting glucose or impaired glucose tolerance. Many of these individuals will eventually go on to develop overt diabetes mellitus. Some experience complications associated with diabetes, even before they meet criteria for formal diagnosis....Performing a two-hour oral glucose tolerance test in those patients considered to be at high risk, may increase the number of new cases identified....Besides being at risk to develop diabetes mellitus, individuals with prediabetes are more likely to have metabolic syndrome, hypertension and other comorbidities. Prediabetes is associated with greatly increased risk of future cardiovascular events. The statement reiterated the importance of aggressive lifestyle modification. Even modest amounts of weight loss of 5-10 lbs have been shown to reduce the risk of developing diabetes. Weight loss can improve the control of hypertension and dyslipidemia. In addition to dietary modification, regular physical activity of about 30-60 minutes a day five days a week was recommended....Although there is no FDA-approved pharmacotherapy for the treatment of prediabetes, the consensus statement did mention metformin and acarbose as possible options in those who fail lifestyle modification alone....Despite the success seen in clinical trials, initiating and maintaining lifestyle modification is met with variable success in the real world. 

I can understand the frustration of physicians who are caring for patients with prediabetes or the metabolic syndrome and who are unable to convince/cajole them to make lifestyle changes. The latter phrase is code for losing weight and pursuing even a modest exercise regimen. Why are so many Americans resistant to these ideas when the alternative is serious health consequences? I asked a cardiologist friend how he persuades his patients to take off extra pounds. He told me that Weight Watchers was the most effective program in his experience, even for hard-driving male executives. An on-line program is available, but I suspect that it is not as effective as the personal interactions and peer pressure of face-time meetings.

What's interesting about the consensus statement referenced above, hinted at by the caveat that there is "no FDA-approved pharmacotherapy for the treatment of prediabetes," is that physicians may be drifting toward off-label use of drugs such as metformin to treat the condition.

CROs Continue to Prosper; Benefits of Big Pharma Outsourcing

I have posted a number of notes about contract research organizations (CROs) in the past, primarily relating to Covance and Charles River. My interest in them has been sparked by the fact that lab testing comprises a large component of the clinical trials that they manage.The news continues to be bullish on CROs, in part because of the active outsourcing of Big Pharma to the CROs which have been quite willing to respond to these new opportunities (see: Lilly outpacing the industry in accelerating its clinical research outsourcing). Below is an excerpt from the article (boldface emphasis mine):

The CRO market was recently estimated at $16.3B for 2006 by Turner Investment Partners with 12.6% compounded annual growth through 2011.  Significant growth drivers are the focus on cost control and emphasis of internal efforts on developing the drug pipeline.This week, Eli Lilly announced three deals with Covance, Quintiles, and i3 that easily could more than double their current level of outsourcing.

• The biggest of these three deals by far is the 10-year, $1.6B deal with Covance selling them their Greenfield Indiana facility for $50M and assuming 260 Lilly employees.  According to Forbes, the Covance CEO says they already do “about $70 million in work annually for Lilly. The new contract will lock that in and add $90 million annually.”
• U.S. clinical-trial monitoring work will be transferred to Quintiles, another large CRO.
• Data management will be transferred to i3, a CRO subsidiary of United Healthcare.

The integration between pharmaceutical companies like Lilly and a CRO like Covance continues with the latter now absorbing some of the former's employees. I have published a number of notes about United Healthcare in the past, but was not aware that the company had a CRO as a subsidiary.

The CROs are obviously expanding their mission statements in response to this eye-popping growth and demand for a broader range of services from the pharmaceutical companies. As one example, here is such a statement from i3 copied from its home page:

Help at every stage of the pharmaceutical product lifecycle

Develop: Focused therapeutic and scientific expertise from discovery to launch.   
Market: The vision to help you realize the full potential of your brands.
Manage: Comprehensive clinical data, drug safety, and staffing services.
Improve: Strategies for monitoring safety and increasing competitive advantage.

Biosurgery and Degenerative Joint Disease

When browsing the Genzyme home page, I came across the fact that one of their EVPs, David Meeker, M.D., is in charge of a business unit called Therapeutics, Biosurgery & Transplant. This reference to biosurgery caught my attention because I had not encountered the term before. Genzyme defines biosurgery on their web site in the following way (see: About Genzyme Biosurgery):

Genzyme Biosurgery is a leading developer of novel biotherapeutic and biomaterial products.  Our products and research pipeline harness the power of biology to improve the health of patients in the orthopaedics and post-surgical adhesive disease areas....The result: a suite of products and product development candidates designed to provide new tools to help improve patient outcomes, reduce the time and complications associated with surgery, and may in some cases, postpone the need for surgery.

Their biosurgery product list for Genzyme is focused on the treatment of degenerative arthritis. Here is a list of company products in advanced testing stages:

• Synvisc (hylan G-F 20) for hip – U.S. Phase 3. Genzyme is conducting a clinical study to evaluate the safety and efficacy of Synvisc in patients with pain due to hip osteoarthritis.
• Synvisc for ankle, shoulder– Europe. Phase 3. Genzyme is conducting several clinical studies designed to evaluate the safety and efficacy of Synvisc in patients with pain due to ankle or shoulder osteoarthritis.
• Hylastan for knee. Phase 2. Genzyme is conducting a clinical study to evaluate the safety and efficacy of hylastan in patients with pain associated with osteoarthritis of the knee.

i discovered after further investigation that biosurgery has two meanings: the first is the use of living organisms such as maggots to clean and disinfect a wound. The second, and obviously the use intended by Genzyme, is defined in the following way (see: Biosurgery):

A second sense has grown up in parallel with it to mean surgical techniques that employ a range of natural or manmade materials. Biomaterials are biologically compatible glues to seal surgical incisions, lubricants to help joint movement, and support on which living tissue is grown or shaped, but the term also covers biocompatible materials such as hip replacements and artificial pacemakers. It also includes biotherapeutic techniques such as gene and cellular therapies.

For me, the use of the term biosurgery in relationship to the injection of, say, Synvisc into a knee joint for the treatment of osteoarthritis is confusing because the only surgery involved is the introduction of the needle into the knee joint. At least in this case, the terms biomaterials and biotherapy make more sense.

Continuing Discussion of the Role of Lab Medicine in Personalized Medicine

In response to my note of last Friday (see: Genetic Testing to Cull Out the "Un-Right Patient" as a Candidate for a Particular Drug Therapy), Dennis Dionne submitted the following comment:

Chemotherapy drugs, i,e.; 5-fluorouracil (5-FU), are dosed by BSA [body surface area]. In the May 2008 issue of the Journal of Clinical Oncology, Dr E Gamelin reported a randomized multi-center study among metastatic CRC [colo-rectal cancer] patients treated with continuous infusion 5-FU whose drug blood levels were monitored and dosing adjusted to achieve target concentrations. Gamelin demonstrated that patients were over-dosed and only 25% were actually in the optimal range. By practicing therapeutic dose management (TDM) to maintain the plasma level of 5-FU within the therapeutic window, patients did much better. They experienced significantly better objective tumor response and doubling of survival at two years, while experiencing significantly less toxicity. Therefore, once the right patient is placed on the right therapy (genetic testing), therapeutic drug monitoring can make sure the right dose correlates with the right plasma level exposure to achieve optimal value.

A very relevant comment and I will return to this later.

In my mind, the definition of personalized medicine, also known as targeted therapy, is becoming more complex. The source of this additional complexity lies in the following new developments: (1) the growing importance of companion diagnostics; (2) the growing importance of medical imaging in both the diagnosis of disease, particularly tumors, and monitoring the efficacy of treatment; (3) the use of genomic and proteomic testing to cull out candidates for drug therapy who may be harmed by it; and (3) the use of medical imaging post initiation of chemotherapy to monitor its efficacy. The most obvious example of this latter approach is to determine with imaging whether a primary tumor or its metastases are shrinking.

Lets start this discussion of personalized medicine with what I considered to be a reasonable current definition from the Wikipedia presented below. To the right I also offer a diagram of an expanded flow diagnostic work flow diagram that encompasses some of the newly emerging nuances of personalized medicine, as I understand them. In the diagram, I include a box at the bottom to represent Dennis' very relevant comment about therapeutic drug monitoring (see above).

Personalized medicine [involves the] use of information and data from a patient's genotype, or level of gene expression to stratify disease, select a medication, provide a therapy, or initiate a preventative measure that is particularly suited to that patient at the time of administration. In addition to genetic information, other factors, including imaging, laboratory, and clinical information about the disease process or the patient play an equally important role.

In this diagram, I distinguish between "mandated lab companion testing" and additional genomic/proteomic testing because the former type of testing is frequently developed collaboratively by pharmaceutical companies and in-vitro diagnostic companies and often required or recommended by the FDA. The latter category may include newly discovered test methods that may clarify the therapeutic picture.

On the basis of this expanded understanding of personalized medicine (targeted therapy), I offer the following expanded definition that I have intentionally kept relatively brief for clarity:

Personalized medicine involves the use of laboratory-based molecular diagnostics and medical imaging to select suitable candidates for treatment with a particular drug(s), to rule out those patients who would suffer unacceptable side effects from the proposed drug treatment, and to monitor the health status of the patient post initiation of therapy to assess therapeutic drug levels and the continuing efficacy of the agent in suppressing or curing the disease.

Genetic Testing to Cull Out the "Un-Right Patient" as a Candidate for a Particular Drug Therapy

The goal for personalized medicine has been drummed into my head using the following mantra: selecting the right drug for the right patient at the right time. However, I have tended to avoid the use of the term personalized medicine, favoring the term targeted therapy. However and not unexpectedly, we have come to another turn in the road regarding the meaning of personalized medicine/targeted therapy medicine due to new scientific discoveries.

My goal for this note is to discuss what I will refer to as the need to cull out the un-right patient as a candidate for a particular drug therapy. A recent article in the New York Times (see: F.D.A. Urges Genetic Test Before Giving AIDS Drug) suggested this idea to me. Below is an excerpt from the article with boldface emphasis mine:

Seeking to prevent life-threatening side effects, the Food and Drug Administration is urging doctors to use a genetic test to screen patients before prescribing a drug widely used for H.I.V. infection and AIDS. In an advisory ..., the agency says that patients with a particular variation in an immune system gene should not be given the drug abacavir because they are at a far higher risk of a severe allergic reaction to the drug....F.D.A. officials said they believed that the genetic test, which is already available from some laboratories, would be quickly adopted for screening patients before prescribing abacavir....A small percentage of abacavir users suffer so-called hypersensitivity reactions, either when they start the drug or when they resume using it after some interval....Based on that data it was estimated that 61 percent of people with the genetic variant — called HLA-B*5701 — would suffer a hypersensitivity reaction, in contrast to only 4 percent without the variant, according to new information on the drug’s label.

In previous notes, I have commented at length about the use of companion diagnostics (see: Consideration of a Broader Definition for "Companion Diagnostics"; A Closer Look at Companion Diagnostics Strategies; Some Interesting Insights into Companion Diagnostics). My understanding of companion diagnostics has been that various lab tests are used to select appropriate candidates to receive a particular drug. In other words, the goal has generally been to select the patients for whom a  drug will be effective. I extended this concept in another note about therapeutic efficacy (see: Moving Resources from the Therapeutic to the Diagnostic Silo) in which I suggested that molecular diagnostics and medical imaging could be used to identify those patients for whom treatment with drugs, particularly expensive chemotherapeutic agents, would be effective. It was overtly stated, however, that this approach would also enable us to cull out those patients for whom the use of a drug would not be effective. In so doing, resources could be saved.

I now understand that we need to expand our understanding and definition of personalized medicine and targeted therapy to include the selection of the right patient AND the exclusion of the un-right patient. By the use of this latter term, I mean both the patient who will not be helped by the therapy and also the patient who will be harmed by the therapy. This may seem like splitting hairs but I do like the notion of using lab testing to identify both the right and the un-right patients.