Double Blind Studies...“Blinded” Is Right

[Guest guest]

" Blinded " Is Right

 

The New England Journal, the Miss Manners of medical practice,

recently published two studies which shattered the sacred cow of

blinded, randomized controlled trials.

Tackling one of the most prevalent myths of the medical trade,

authors Arthur J. Hartz, MD, PhD and Kjell Benson, BA found " little

evidence that estimates of treatment effects in observational studies

reported after 1984 are either consistently larger than or

qualitatively different from those obtained in randomized, controlled

trials. " The second study, by John Concato, MD, MPH came to the same

conclusion. And while these studies deal with cardiovascular and

other diseases, the implications for cancer, I think, are similar.

Predictably, an attempt was made to stanch the bleeding. The

articles were followed by a critical review that impugned the

landmark findings. You don't trash sacred dogma without meeting

resistance.

For as long as I can remember, academicians and doctors of high

estate and low sensibility, have worshipped at the altar of the

Randomized Double-Blind Controlled Trial. Cancer patients tend to

steer clear of them, despite the warm invitation of researchers whose

livelihoods depend on them. Only two out of 100 patients volunteer.

Panic and confusion are frequent fellow travelers with a

diagnosis of cancer. Many doctors discourage their patients from

exploring other options. Hospitals and clinics usually do not discuss

alternatives because their incomes are dependent upon the amount of

chemotherapy they can prescribe. One mediocre oncologist, fired for

incompetence, was rehired later because whatever the diagnosis, as

one hospital official put it: " He could always come up with an

expensive chemotherapy protocol. "

In a randomized, controlled trial, usually there is only a 50/50

chance of getting the desired experimental treatment. It is chance,

not the patient, which decides whether one is assigned to the

experimental arm or the placebo arm of a trial. Once one surrenders

one's choices to a drug company the die is cast. The transformation

of a human being into a guinea pig is an ominous process.

The advantages of non randomized trials are many. They're hugely

cheaper. Quicker. And they may be tried on a greater variety of

patients. And if the results are almost always the same, where did

the tenet of randomized trial superiority come from? The Journal's

authors point out that studies of the 60s and 70s were lacking in the

improved methodology of the 80s and 90s, among which more reliable

statistics and choice of data.

Exploring some 3,868 observational studies, the authors narrowed

the list to 19 similar studies in which there was both a randomized

trial and an " observational " study. In only two of them was there a

discrepancy in interpretation of the magnitude of treatment effects.

Europeans often regard the double-blind, randomized, controlled

trial as an unethical practice. I remember the Robert Janker Klinik

medical director, Dr. Wolfgang Scheef, being grief-stricken at the

outcome of a particular randomized controlled trial of his discovery,

Mesna, a rescue agent for an entire class of drugs such as Cytoxan

and Ifosfamide. Three young soldiers with testicular cancer, who were

randomized to the placebo arm of the study, died from ifosfamide's

toxicity. The experiment was deemed a success and the results were

published in the NCI journal Cancer Treatment Reports.

Scheef felt personally responsible for the fatalities.

" There was no need for such a trial, " he complained. " Mesna had

never failed among the hundreds of patients on whom it had been tried

heretofore. You do not need a comparison other than the historical

controls for something as obvious as this. Previously, ifosfamide was

thought a most dangerous drug. With Mesna, it no longer kills. "

The traditional problem with these drugs was the urinary tract

problems. The chemotherapy attacked the kidney, the bladder, and the

urethra. Ifosfamide was temporarily withdrawn from marketing by its

manufacturer, Asta Werke, after 14 South African patients died of

drug-induced cystitis and hematuria.

I scarcely ever suggest that cancer patients resort to

experimental trials because they rarely produce a positive outcome

for the patient.

Maurie Markman, MD, formerly of Sloan-Kettering Memorial

Hospital, reported in a 1985 article in CA – A Cancer Journal for

Clinicians, that in a series of Phase I clinical trials on 1,248

patients coordinated by the National Cancer Institute, " the complete

plus partial response rate (a 50% or greater decrease in the product

of the perpendicular diameters of measurable tumor masses) was only

2%. Only two patients (0.16%) achieved a complete remission…. "

Where were the benefits for the patients? Where were the benefits

for " posterity " ? Well, at least the drug companies got to find out a

little more about their products and create another step forward

along the tortuous path of FDA approval. I don't know of any of the

current " approved " chemotherapy treatments for cancer that are

totally safe or convincingly curative. But they have a long paper

trial.

And, in this world of scientific propriety, that's what counts.

Never mind what happens to the patients.

 

Patrick McGrady

CANHELP

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Port Ludlow, Washington 98365 USA

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