How We Do Harm (29 page)

By 1995 AHCPR had dared to examine spinal fusion procedures, one of the great cash cows of medicine, and as a result of venturing into this dangerous territory, the agency nearly lost its funding.

One of the PORTs had published a study reviewing the literature on surgery for low-back pain.
It found little evidence to support spinal fusion surgery and noted that such surgery commonly had complications.

The North American Spine Society (NASS), a specialty group, attacked the literature review and the subsequent AHCPR practice guidelines.
In a letter published in the journal
Spine
(1994), NASS not only criticized the methods used in the literature review, but expressed concern that the conclusions might be used by insurers to limit the number and types of spinal fusion procedures.

Congressmen Henry Bonilla (R-TX), Gerald Solomon (R-NY), and Joe Barton (R-TX) led the effort in the House to end the agency’s funding, claiming, of course, that AHCPR was supporting unsound research and wasting taxpayers’ money.

The agency was in serious jeopardy of being abolished just six years after it was formed, but some last-minute political maneuvering secured a reprieve.
Representative John Porter (R-IL) and Speaker Newt Gingrich (R-GA) came out in favor of saving the agency.
Senator Arlen Specter (R-PA) was chair of the Senate Appropriations Subcommittee on Health.
He was lobbied by supporters of the agency as well as its detractors.
The eventual House-Senate conference committee decided to cut the AHCPR annual budget by 21 percent.

This story was widely reported in the news media.
The spine surgeons were upset that someone would dare to say that bed rest and physical therapy were often more effective than spinal laminectomy.
The self-serving surgeons were saying the hell with what the science says, and everyone else was apathetic or worse.

That a federal agency could face a threat of “defunding” and ultimately end up with a catastrophic budget cut as punishment for telling the scientific truth was noticed by those in government.
This realization has influenced decisions by officials of the Food and Drug Administration, Centers for Medicare and Medicaid, and others.
Shortly after the AHCPR punishment, the National Cancer Institute director, Richard Klausner, was confronted with mammography-screening recommendations for women in their forties.
His final decision had to be based not on the science as much as on the politics.
Had he pissed off Congress, the NCI would get an AHCPR-like punishment.

His career would be over, too.

Naturally, he caved.

PART IV

Evidence-Based Medicine

Chapter 19

The Denominator

ASK JUST ABOUT
anyone you see in the street whether screening for prostate cancer saves lives, and the answer would be yes.
“Find it early” is a truth akin to “more is better.”
It seems obvious that finding cancer early is better than finding it late or not finding it at all.
But linear thinking and logical conclusions have time and again gotten us into trouble in medicine.
The single most important aspect of clinical research is to identify the fundamental scientific questions.

In prostate cancer, I see three questions that need to be addressed if we are to stop doing harm:
• Does treatment of localized prostate cancer save lives?
This question comes first, because if we are unable to improve the prognosis for men with prostate cancer through treatment, early detection would be useless or harmful.

• Which modality is most effective in treating early-stage prostate cancer?
Is it radiation therapy or surgical radical prostatectomy?

• Does screening for and identification of early-stage disease save lives?
How can we identify the cancers that are a threat to a man’s life and need to be treated from those that are not a threat and need to be watched?

Believers in screening have by and large rejected these as legitimate questions and have worked hard to prevent us from answering them in the clinic.
Yet, until we know the answers, we will not be able to address the most important question of all:
What’s a man to do?

*

PATIENTS
pay doctors to be decisive.
“Hell if I know” is not on the menu of answers one expects from a health professional.
Yet, every doctor I respect readily acknowledges limits to his or her knowledge.
As a profession, we have an even higher duty to recognize what we don’t know and ask questions responsibly.
Here is how I learned:
In 1989, after six months of training at the NIH Clinical Center, I was rotated to the National Naval Medical Center.

The navy hospital is just across Rockville Pike from NIH, but I would soon learn that the intellectual divide between the two campuses far exceeds the physical distance.
Though doctors who ran the navy’s cancer program were technically on NCI staff, the intellectual atmosphere they created was more collegial and more conducive to critical examination.
These were the doctors who watched with dismay as we were causing paralysis in adrenal-cancer patients.

By the time I cross the road, I have been thoroughly trained and indoctrinated as a soldier in the army of cancer treatment.
I have my doubts, but I am still a can-do kind of guy who dispenses hope.
One of my first patients is a young black woman with a Dukes’ B colon cancer, Stage II disease, with a bulky tumor, but no spread through the lymph nodes.
The tumor had been surgically removed.

Since she is so young, I decide to give her the most aggressive treatment available in 1989, 5-FU and levamisole, a drug that is believed to make 5-FU work better.
Studies at the time show that 5-FU and levamisole produce better disease-free survival, compared to no treatment, in later-stage disease, Dukes’ C colon cancer.
If it works in Dukes’ C, why shouldn’t it work in Dukes’ B?
This seems logical.

I present the case—and my treatment plan—to the attending.
This was my first encounter with Barnett Kramer, a slightly built man who is both intensely knowledgeable and proudly nerdy.

“The data to suggest that 5-FU works in Dukes’ B are mighty skimpy.
It’s really a stretch,” Kramer says after hearing my idea.

“I understand that, but this is a young woman, and using chemotherapy to reduce her chances of a recurrence may be a gamble worth taking,” I object.

“This does make sense, but you can actually harm people by using science that appears to make sense, as opposed to science that has been proven to be correct in a clinical trial.
Worst case, she will get none of the benefits while suffering the side effects.”

I realize that while the warlords across Rockville Pike are trumpeting therapies and promising cures, Kramer is calmly suggesting that those same therapies may do harm while doing no good.
This is the first example of skepticism I encounter in Bethesda, and it impresses me immensely.
This is also the beginning of Otis understanding the value of a clinical trial and being orthodox to the scientific method.

I want to know more, and over the months that follow, Kramer is happy to answer questions.
These conversations usually take place on the third floor of Building 10, one of the low buildings adjacent to the New Deal tower.
Sometimes we talk over lunch, joining the navy cancer program’s deputy director, Daniel Ihde, and the program’s director, John Minna.

The paucity of our cancer armamentarium is a common subject of conversations.
This is different from the official line you hear across Rockville Pike: the drugs we have are highly effective.
The problem is reaching “dose density” without killing the patient.

It’s not necessarily so, say my new mentors, listing the unproven conjectures that go into the belief that more is better.
Just as easily, more can give you higher toxicity without any additional efficacy.
More can be worse.

These guys are particularly effective mentors.
Instead of approaching fellowship as an apprenticeship, wherein the young doctor watches the attending, they teach you to think for yourself.
That trio—particularly Kramer—move me in the direction of studying the design of clinical trials.

*

DURING
one of these conversations, Kramer tells me about his intellectual journey.
As an academic physician at the University of Florida, he found himself drawn to trial design and statistics.
Early in his career, doctors found effective treatments for childhood leukemia, testicular cancer, and Hodgkin’s lymphoma.
However, going forward, Kramer doesn’t foresee many big cures.
What he does see is a need for prevention.

To branch out into that discipline, Kramer attends an intensive weeklong statistics course at Harvard.
This only reaffirms his desire to get additional training in trial design and epidemiology.
He plans to take a sabbatical at the University of Florida, but Ihde prevails on him to accept a job at Naval.
He still plans to pursue a public health degree, but it will have to wait.
Meanwhile, Kramer knows enough about the subject to completely transform my thinking about cancer.

Until these conversations, I thought of cancer exclusively as a clinical problem.
A clinician deals with one patient at a time, paying no attention to impact on the burden of disease.
Now I start thinking of the problem as a simple fraction.
As a clinician, I can easily get trapped into focusing exclusively on the numerator—the patient I am taking care of.
I pay no attention to the denominator, a population of patients.
This distinction is particularly important in screening.

Before you declare a screening test a success, you need to determine how many people you have to screen to detect one instance of disease and how many people you have to screen and treat to save one life.
At what point is screening worth the trade-off?
What kinds of studies do you need to conduct before you pronounce your test successful?

These questions would change the direction of my career.

Chapter 20

From the Health Fair

SHORTLY AFTER HE TURNS SEVENTY,
Ralph DeAngelo, a retired department-store manager, sees a newspaper ad placed by a local Midwestern hospital.
The ad says that prostate cancer screening saves lives.
It notes that 95 percent of men diagnosed with localized disease are cured.
They survive.
The ad notes that a local hospital is offering free prostate-cancer screening at a suburban shopping mall during something called Prostate Cancer Awareness Week.

Actually, Ralph isn’t the one who notices the ad.
He is healthy enough, and he wants to stay that way.
Yet, his wife’s admonitions notwithstanding, Ralph doesn’t frequent doctors’ offices.
I agree with this approach to life, but Ann DeAngelo doesn’t.
She loves Ralph, needs him, and this preemptive test for a deadly disease would keep him around for years to come.
Ann’s reaction to the ad isn’t an accident.
Campaigns promoting prostate-cancer screening are designed to be noticed by wives, who convince their husbands to get tested.

Ralph doesn’t put up a fight.
Why would he?
He has the time.
He is retired.
Time isn’t scarce.
Ralph decides to go, to appease Ann, to stop her worrying, to make her feel more secure about his health, his age, his ability to be there for her.
He shows up at the appointed place and waits in line for nearly two hours.
The health fair is held in an empty storefront that had been occupied by a succession of five-and-dime stores.
It’s a maze of partitions, card tables, and balloons.
Music of the fifties, and certain kinds of music from the sixties and seventies, create a celebratory feeling.

Guys from a local chapter of a support group called Us TOO International Prostate Cancer Education & Support Network are all around, greeting you, trying to start conversations.
The health fair gets men screened and out quickly.
It’s simple enough.
There is no information to take home, no fine print to stumble through, no documents to describe pros and cons.
Ralph does fill out a form asking the usual: name, address, date of birth, phone number.

The form doesn’t ask for his insurer’s name and number, but it does ask whether he is insured and whether he has Medicare and Medicare coinsurance.
This seems odd: wasn’t this affair billed as a
free
screening?
Ralph fills out the forms and waits for his name to be called.

Finally, he steps behind a hospital-blue cloth screen.
A urologist in a white coat has him drop his pants and bend over.
It’s a digital rectal exam.
Ralph has had those before.
It’s just a small indignity that comes with being old.
Almost anything is better than the alternative, he thinks as the urologist’s index finger draws a sweeping motion inside his rectum.

Ralph rolls up his sleeve to get blood drawn for a test that will measure the level of prostate-specific antigen, or PSA, that famous test that, according to the ad, saves lives.
Done.
Ralph is free to go on with his life.
Ann is officially off his back, appeased.

Two weeks later, a letter from the health system shows up.
Ralph’s PSA is elevated and he needs to contact a particular office at the hospital.
The letter notes that most abnormal PSAs aren’t due to cancer.
Still, Ralph’s test results are significantly abnormal and should be evaluated.
Ralph calls the office and gets a referral to a urologist, Philip Moore.
Two weeks later is the closest thing they have.
Ralph makes the appointment and settles in for the two weeks of hell that follow.

Usually an even-keeled guy, he realizes that he is scared out of his wits.
It seems every thought he has begins with cancer or ends with it.
Kids and grandkids find out.
They, too, worry.
Ralph is particularly troubled about some numskull’s telling his thirteen-year-old granddaughter.
He learns about this the hard way.
“Grandpa, are you going to die?”
the teary-eyed girl asks him.

Ralph reads up on Moore.
The doctor is in his fifties and has been practicing in town for more than twenty-five years.
He is part of a five-man group affiliated with a respected local private hospital.