“Big Box” American Medicine

Over the last several months we have been engaged in construction work on our home. The kitchen and adjoining rooms required new floors. To accomplish this goal, we went online and examined the types of floors, patterns and qualities that met our needs. We shopped at various venues including small privately-owned flooring shops and larger national chains. The one-stop-shopping aspect of the larger chains (cabinetry, flooring, carpets, appliances, etc. all under one roof) had a certain appeal. After considering our options we proceeded with one of the chain stores. Although we greatly appreciated and respected the expertise of the consultant who worked with the big box store, the results proved less satisfactory.

First, we needed our space measured. The big box store contracted with a group who did their flooring measurements. Second, we needed to purchase the material. This was done through the large concern acting as our purchasing agent. Finally, after the several weeks delay for the “special order materials,” our flooring material was delivered to yet a third party, the flooring installation experts.

Despite the delays, everything was moving along reasonably well. And then came the problem. Our contractor had needed to resurface a section of our entranceway. This left a gap from the bare wood up to the existing surface that was about to be recovered by the installation staff. We contacted the installation group the night before their scheduled   arrival to explain that they would need to match the new surface level with that of the old one. And then the wheels came off.

“We can’t do this job for a fear that there could be a need for asbestos remediation.”

“What asbestos?” I responded.

Their response, “We don’t know, but it’s a possibility.”

“Well then, come out and take a look.”

“Oh, no, we can’t do that, it will be at least a week.”

I felt stymied. Our carefully scheduled flooring, followed by appliance replacement, followed by painting, followed by cabinetry installation was now on indefinite hold. Luckily, I had a personal contact with a privately-owned flooring company who provided their own installers. They arrived the next day, examined the situation and explained that there was no asbestos risk whatsoever. They neatly matched the floor levels using a plywood sheet and proceeded to perfectly complete the flooring job.

After all was said and done, I suddenly realized that I had almost double the flooring material I actually needed. After much discussion, we convinced the big box store to accept the excess material in return and to compensate us for the difference.

So what’s this got to do with medicine? Quite a lot I would suggest.

Like the big box stores, American medicine is migrating towards generic care with each function contracted out to a different entity. The internist who diagnoses the problem is then forced to refer the patient to an outside contracted diagnostic service provider (i.e. radiology, CT, MRI). Results then slowly percolate back to the primary care physician who, one or two weeks later, recognizes the problem and recommends hospital admission. At this point a contracted hospitalist starts all over again, examining the patient and taking a detailed history in an attempt to uncover that, which the internist already knew. With the best data the hospitalist can accumulate, he then turns again to a contracted provider for a final intervention. The patient all the while has waited weeks, undergone numerous  interventions and investigations and more often than not gets more, or in some circumstance less, than what they really needed.

As we continue to undervalue the abilities and expertise of individual private physicians functioning as quarterbacks in patient management, we abdicate the management of a patient’s delicate problems to the intersecting tectonic plates of medical systems: HMO, PPO, VHA, Medicare, HHS, AARP, etc., etc., etc.

Like the big box stores that adequately meet the average needs of the average customer with an average problem, these medical behemoths lack the insight to meet individual patient needs. Duplication of services and inefficiency are the inevitable result. In retrospect I would gladly have paid a slightly higher fee for a privately owned concern to have measured, purchased and installed my kitchen floor. The savings associated with big box stores, are like those associated with HMO care . . . nonexistent.

So long as you are 42 ½ years old, have a viral respiratory infection and don’t have any allergies or prior medical history, HMOs provide great care. For everyone else,  Caveat Emptor!

The Avastin Saga Continues

We previously wrote about bevacizumab (Avastin) and its approval for breast cancer. The early clinical trials revealed evidence of improved time to disease progression. This surrogate measure for survival benefit had, over recent years, gained popularity, as time to disease progression is a measure of the impact of a given treatment upon the patient’s response durability. It was hoped and believed that time to progression would be an early measure of survival.

Unfortunately, the survival advantage for the Avastin-based therapies in breast cancer has not met statistical significance. As such, careful review by the oncology drug committee of the FDA lead to a unanimous decision to remove Avastin’s indication in breast cancer. Avastin has not been removed from the market, but instead, cannot be promoted or advertised, nor do insurers necessarily reimburse it. This decision, however, will have a very big impact on Medicare patients and many others who are in managed care programs (HMOs).

There are no villains here. Instead, dedicated physicians empowered to scrutinize the best data could not prove beyond any doubt that the drug improved survival. The time to progression data was favorable and the survival data also trended in a favorable direction. But, the final arbiter of clinical approval — statistically significant survival — was not met.

The physicians who want to provide this for the patients, the company that produces the drug and the patients who believe it offers benefit all have legitimate positions. As Jerome Groopman, MD, once said, in a similar situation with regard to the FDA approval of interleukin 2 (a biological agent with profound activity in a small minority of melanoma and renal cell cancer patients), “I am confronted with a dilemma of biblical proportions, how to help the few at the expense of the many.”

The Avastin saga is but one example of what will occur repeatedly. The one-size-fits-all paradigm is crumbling as individual patients with unique biological features confront the results of the blunt instrument of randomized clinical trials. Our laboratory has been deeply involved in these stories for 20 years. When we first observed synergy for purine analogs (2CDA and fludarabine) with cytoxan, and then recommended and used this doublet in advanced hematologic malignancies (highly successfully, we might add) we were a lone voice in the woods. Eventually, clinical trials conducted at M.D. Anderson and other centers confirmed the activity establishing these treatments as the standards of care for CLL and low-grade lymphoma.

The exact same experience occurred in our solid tumor work when we combined cisplatin plus gemcitabine in pancreatic, ovarian, breast, bladder, lung and other cancers. While our first patient (presumably the first patient in the world) received cisplatin plus gemcitabine for drug-resistant recurrent ovarian cancer in 1995 — providing her an additional five years of life — it wasn’t until 2006 that the FDA approved the closely related carboplatin plus gemcitabine for this indication.

We now confront an even greater hurdle. With our discoveries, using novel combinations of targeted agents, we are years (perhaps decades) ahead of the clinical trial process. We know that patients evaluated in our laboratory with favorable profiles can respond to some of the newest drugs, many of which have already completed Phase I of clinical trials. It is our fervent belief that we could accelerate the drug development process if we could join with the pharmaceutical companies and the FDA to put these hypotheses to a formal test.

Again, there are no villains here. Patients want, and should, receive active drugs. Doctors should be allowed to give them. The drug companies want to sell their agents and the FDA wants to see good therapies go forward.

The rancor that surrounds these emotionally charged issues will best be resolved when we introduce techniques that match patients to active therapies. We believe that the primary culture platform used in our laboratory, and a small number of dedicated investigators like us, may be the answer to this dilemma.

We will redouble our efforts to apply these methods for our patients and encourage our patients to lobby their health care insurers and representatives to sponsor these approaches. To date, we have been unsuccessful in convincing any cooperative group to test the predictive ability of these selection methodologies. In response, I reiterate that I will gladly participate and, to the best of my ability, support at least the laboratory component of any fair test of our primary culture methodologies.

We stand at the ready for the challenge.