The Empire Strikes Back A Series of Critical Reviewsof Claims Made on Behalf of New Incontinence Products By John D. Perry, PhD |
Many years ago I had an especially heartbreaking patient, a young boy with nearly constant incontinence due to a developmental defect, supposedly brought on by eating lead-based paint in his apartment.
He was brought to our biofeedback clinic as a last ditch effort prior to an implant of an artificial (urinary) sphincter. His mother drove the 10-12 year old boy over 100 miles each way for training. The initial evaluation showed that his sphincter muscles were extremely weak, with little or no control.
The kid was ecstatic about this new hope, as his leakage was becoming a social barrier at school. Naturally, the family was poor and could not afford a home trainer, so we provided an inexpensive computer EMG interface and prototype of the future "single user" EMG sensor for him to use between office visits.
Over the next three months he was faithful in his practice, and even plotted his daily EMG scores on his home computer (I think it was an Atari!). He was thrilled that his muscles were getting stronger, and his symptoms had begun to improve significantly.
One day, without warning, his mother returned the EMG equipment and cancelled his future appointments. She explained it was necessary because he was gaining urinary control with biofeedback, and this would jeopardize his chances for an artificial sphincter, and that, in turn, she explained, would endanger his million-dollar lawsuit against the lead paint manufacturer! I never saw or heard from the kid again. I hope he won, because he's going to need the money now.
I have no problem with artificial sphincters implanted in 70 year old men who have 20 years or less to live. But since the majority of urethras erode in 20 years, I have real problems with using them on 12 year old kids who plan to live another 60 years.
I'm sure his surgeon was told that "biofeedback didn't help", and why wouldn't he believe the mother?
BTW, back in 1987 AMS almost bought my invention, the EMG sensor. I was terribly impressed with their "clean room" manufacturing facilities, which included computer tracking of every part of every sphincter from assembly to implant to burial.
When artificial sphincters were first approved, it was a god-send to the post-proctatectomy patient population, and we all cheered. Little did we realize that over 20 years the "criterion" level would be gradually relaxed to include 12 year old kids.
The same thing has happened, BTW, in the case of Artificial Penile (erection) implants. Originally they required "proof" of organic basis, but over time that criteria was also reduced, so that now any man who isn't getting along with his wife this week can get one.
With this historical perspective, you can be sure that my antenna was up when the advocates of implanted electrical stimulators began to push for FDA and professional approval.
One sentinel event occurred at the 1988 Consensus Development Conference in Bethesda. At the end of the implanted e-stim presentation, a panelist, Dr. deGroot, asked:
"Isn't it true, doctor, that human beings come equipped with their own built-in stimulators?"
We were firmly assured that this implanted device was intended ONLY for that large and pathetic population that could not learn to use their built-in stimulators - Quads and MS, for example, and everyone cheered.
Dr. deGroot was referring, of course, to very clear studies which show that voluntary contractions of the pelvic floor produce EXACTLY the same effects as external electrical stimulation of the anus, pelvic floor, or nearby areas. In order words, so-called "Kegel exercises" are also effective for treating URGE incontinence.
But many people, having heard that Kegel treated Stress Incontinence, aren't aware of this. I've even seen clinics who treat "only" SUI, not Urge, with biofeedback.
We discovered the effectiveness of Pelvic Muscle Exercise during the original "clinical trials" of our EMG biofeedback system, in our Bryn Mawr, PA clinic in 1985-1988.
First we advertised only stress incontinence (following Kegel). But we got some "mixed" patients, and they reported that "By the way, my urgency has gone away too!"
Then we started accepting pure urge patients, and sure enough, they responded at least as well. (See
http://www.incontinet.com/effective.htm for more on this. Some sensory urge patients may need general relaxation training to supplement pelvic muscle work.)
Back in 1989, Life-tech was thinking about selling our now-popular EMG biofeedback system, and I was invited to attend their famous Urodynamics Training Course as part of the start-up.
I was especially interested when the course leader, the famous Dr. Webster of Duke, explained with enthusiasm the reflexive mechanism whereby the urgency of the bladder is inhibited.
Webster told the audience about the common event of a person driving down the highway, miles from any service station, who suddenly needed to urinate.
"So," he said, "you pull off the side of the road and step behind your car, when suddenly a school bus full of kids comes around the bend. So you squeeze your pelvic muscles, and bend over slightly, pretending to be examining the wild flowers."
"Then," he said, "after the school bus disappears, [and this is the important part] it may take as long as 10 minutes to re-start the micturition reflex and actually void."
I respectfully waited until the urgent questions were asked, and then, from the back of the room, said: "Dr. Webster, this is fascinating. Do you suppose that if people learned to do that muscle tightening, they could quiet their over-active bladders? We could make a whole "therapy" out of that insight!"
"No," he said, "it wouldn't work. Next question?"
I didn't have the heart to tell him that that's EXACTLY what people in biofeedback clinics across the country are already doing every day with complete success. He probably wouldn't have believed it, anyway.
This is the context in which I received the news that Medtronics now has a website for their new InterStim implantable electrical stimulation device. It's
http://www.interstim.com, and links to the main Medtronic site, http://www.medtronic.com. As is common these days, there are sections for "patients", "doctors" and "investors".There is an extensive and fascinating page on the history of the company, which apparently has had a long and honorable career in implanted heart pacemakers. Somehow omitted from that page, however, is their bungled attempts at biofeedback (with Verimed), and TENS (before the insurance crackdown) as well as external electric pelvic muscle stimulators.
The InterStim(r) site explains, with good graphics and careful text, that the device is
"now approved for urinary urge incontinence, urinary retention and significant symptoms of urgency-frequency in patients who have failed or could not tolerate more conservative treatments."
I didn't expect to have trouble right in the first paragraph, but tell me -- what patients exist that "could not tolerate" more conservative treatments? Behavioral Treatments, according to the AHCPR, do NOT HAVE side effects. What do they mean? (Answer below!)
For that matter, what patients have "failed" them? I've never met such a patient, so let's see if they can figure out to whom they might be referring. I began to explore the website.
I first clicked on the health professional information link, which brought up "The Challenge". According to Medtronic, there are only "limited treatment options" available to urge incontinence patients.
Really? Somebody ought to tell the AHCPR. They were able to describe quite a few that are highly successful.
And, we are told, according to a NAFC 1996 survey, "66%" are "not satisfied" with their treatment outcomes.
However, we aren't told what treatments they didn't like. Based on previous articles in this series, that figure would seem to indicate they were taking the well-known pharmaceutical solution, which has a similar dissatisfaction/drop-out rate.
Then we read:
"In fact, treatments for this condition have changed little over the past two decades."
Apparently Medtronics has forgotten its own involvement in biofeedback or electrical stimulation, and did not read about these developments in the AHCPR GUIDELINE.
In fact, the available treatments have changed dramatically over the past two decades. This is a flat-out lie!
Finally, we are told that the "revolutionary approach" of implanted e-stim, also known by it's $10 names, "neuromodulation" or "neurostimulation", has proven to be "dramatically successful."
Let's jump right to the link "Multinational Multicenter Clinical Study Demonstrates Dramatic Efficacy" -- that sounds interesting!
The study page explains that a total of 58 patients have been implanted with the InterStim device. They had previously had apparently unsuccessful outcomes with prior surgery (71%), non-surgical interventions (81%) and medications (91%).
There is no detail about the nature of the surgery, however, nor the non-surgical interventions. If any of them tried biofeedback, we aren't told that.
So, the "dramatic" bottom line? "Twelve months after InterStim Therapy, 75%, [sic] of patients had a successful outcome (>50% reduction of incontinent episodes): 47% of the patients were completely dry. An additional 28% had over 50% reduction in frequency of incontinence episodes per day."
When we look for the peer-reviewed (or otherwise published) source for this statement, we are told only that there is "data on file. Medronic, Inc." Not exactly what I wanted to hear, actually. There is no clickable to order it.
Since that is the sum-total of the evidence presented, we'd better take a closer look.
First of all, we have no idea what the "before" and "after" leakage figures were, so we don't know if we are dealing with a "mild", "moderate", or "severe" patient population.
If the average was "over 30" before, that would be very different from "over 5" before, wouldn't it?
Those who are familiar with E-Stim research, or with previously published critiques of it (for example, see
http://www.incontinet.com/estim.htm) know that there is a big and tricky difference between "symptoms" improved and "patients" improved. In general, we have found that when a 50% symptom improvement is reported in "patients", it corresponds to a overall symptom reduction rate of only one-half as much.Thus, to report that 75% of the PATIENTS improved at least 50% is equivalent to about a 37.5% overall reduction in the SYMPTOMS themselves (leaks).
So, the bottom line is that implanted e-stim is about half as effective as biofeedback, and about equally effective as externally-connected e-stim --- for about 20 to 100 TIMES more MONEY, per patient. "Nice work, if you can get it."
Interestingly, there is no mention on the InterStim website of the cost of their pacemaker-like device, so we have to guess.
Footnote: A few days after this was written, the New York Times carried an article which estimated the cost at $25,000 per implant -- 20% higher than I had guessed. So make that "for about 25 to 120 TIMES more Money".
And that does NOT include life-time expenses following implant failure, nerve erosion, repeated surgery, etc. Depending on the age at implant, many patients could look forward to 50 more years of on-going expense --- just to avoid learning to do their Kegel Exercises!
In the first part of this review (4a), we discussed the 'Multinational Multicenter Clinical Study" of 58 patients posted on the InterStim(r) website. They reported a 75% PATIENT improvement, which corresponds to about a 38% SYMPTOM improvement, typical for electrical stimulation and no better than direct-coupled stimulation.
We were planning to review the several papers cited on the InterStim website, but could only find two of them conveniently. Fortunately, an East-coast Urologist received literature the old-fashioned way, and forwarded the Medtronic packet to us. It includes a "Summary of Multi-Center Clinical Study" as well as Medtronic's own synopsis of seven supportive journal articles.
Ordinarily one expects dead-tree editions to be older than internet publications, but apparently that isn't true here. While their website lists only 58 implants, the hard copy edition describes a whopping 581 patients! And, like the 58 patient study, there is no indication that this data has been or ever will be published in any peer- reviewed journal. (But more on the 7 that were, below.)
Apparently the 581 data was collected during experimental trials, because we are told that while FDA approved the InterStim for urge incontinence in September, 1997 they only approved "urgency-frequency" and "retention" in April, 1999, and this study reports on all three problems.
There was a total enrollment of 581, including: 184 - Urinary urge incontinence 220 - urgency-frequency symptoms 177 - urinary retention A crucial element of the InterStim protocol is that the patient must first demonstrate a satisfactory reaction to externally-mounted stimulation in order to get an implant.
As one of their subjects wrote on the internet:
the TRIAL is a box that you carry with you. They test it on a temporary basis to see if it helps you before they go in and put wires in you permanently. You have a wire coming out of your back that is attached to the box. The box, which is a bit bigger than a beeper, controls the stimulation. It has the battery in it too. I had to have this temporary wire done 3 times before I qualified for a permanent implant-that's a long story for another time!! Anyway, they leave it in for a few days and monitor your bladder function. If it helps, you qualify for a permanent implant.
According to their report, only 260 of the 581 patients, or 45%, met even the minimal requirement of having at least a 50% symptom improvement in the test trials. Of these 260, only 219 persons, or 38% of the original subjects, were actually implanted with the device. If you are looking for hard numbers, this is the end of the line.
All of the efficacy data is reported ONLY in terms of percentages. We have no idea how many urge patients there were; we are only told that "79%" had a "statistically" significant reduction in symptoms of at least 50%. We have long maintained that a 50% reduction in symptoms was CLINICALLY insignificant, even if it was "statistically" significant. 50% reduction only means going from 6 pads a day to three pads a day -- hardly anything to write home about.
But bear in mind that ALL of these patients had a 50% reduction in the TEST trial BEFORE they were even considered for the implant. In other words, the externally-mounted box had proven 100% effective with these patients, but the surgically implanted version was only 79% effective. Very strange.
And we haven't even considered the 55% who did not respond to the TEST, either. Of those who volunteered for InterStim, only 36% eventually achieved 50% continence with the implanted device. (And that corresponds to a symptom reduction or "Burgio" result of 18%, about the worse outcome on record!) Well, what about frequency? We are told that 83% of implanted patients had "clinical success"!
Wow, what does that mean? Only that they had "increased voided volumes (any amount of increase) with the "same or reduced degree of urgency". Hmm. Furthermore, 33% of the implanted frequency patients reduced their voids by at least 50%.
And an additional 31% (additional to what?) who had more than 7 voids now have less than 4-7 voids a day. We have no idea what this means, because there are no numbers, only percentages.
Finally, there is "retention". 61% of the implanted patients (an unknown portion of the original 177) got off catheters. Less than 2/3. The researchers also employed an "A-B-A" design, or actually, a "B-A-B" design, to show the effectiveness of stimulation.
We are told that 52 Urge patients had 10.8 leaks per day in the baseline period, 2.9 leaks per day during stimulator use, and then 9.5 leaks when the stimulator was turned off. This difference is "statistically" significant (p<0.0001), which sounds like a big deal, until you consider that they are still having 3 leaks every day, even with a $25,000 implanted stimulator!
Pat Burns' "moderates" had 12-13 leaks per day, her "milds" had 4; so we are talking about a patient population that went from "low-moderate" to "low-mild" incontinence, Any way you look at it, the implanted patients were STILL "incontinent" AFTER InterStim therapy!
Likewise the frequency data. InterStim patients went from 16.3 voids per day baseline to 8.6 voids per day WITH stimulation. But ICS defines "over 7" as incontinent, so they, too, were also "incontinent" AFTER therapy.
PEER REVIEWED LITERATURE
The other Medtronics packet contains synopses of seven published journal articles dealing with "sacral root neuromodulation". Interestingly, the packet begins by noting that "pain" and "stress incontinence" are NOT approved indications for InterStim in the USA. But that doesn't stop Medtronic from summarizing articles that promote such off-label uses.
Two articles are by Shaker HS and Hassouna M in the Journal of Urology, 1998, vol. 159. In one study, 20 patients with retention lowered their post- void residual from 78% before to "5 to 10%" after implantation. [They also decreased a pelvic pain score by 50%, but don't do that in the USA!] In their second study, these authors treated 18 patients for Urge Incontinence. They lowered their leaks from 6.5 to 2 per day. Not a big deal; from high-mild to low-mild, they are still incontinent.
In a 1995 study by Bosch JLHR and Croen J, 31 patients were screened and 18 implanted. 83% of them had a 50% or better improvement in urge symptoms, for a "Burgio" rate of about 41% of the implants, or about 20% of the patient population. However, 5 of the 18 required repeated surgery for mechanical reasons.
Elabbady AA, Hassouna MM, & Elhilali MM, in 1994, studied 17 patients. They had an initial pool of 50 patients who were tested, but used a high standard, 70% improvement, for final implants. 8 retention patients increased their output from 23% of bladder capacity before to 82% after. And although they had used 4.2 intermittent self-caths before, they were still using 1.3 per day after. In other words, the average patient with a $25,000 implant was still self- cathing MORE THAN ONCE A DAY.
In another mixed group of 9 patients with "other dysfunctions", there were modest gains, of 37% (frequency) to 85% (pain-and-difficulty-starting-to -void, whatever that means). Overall, however, there were complications in 8 of the 17 patients, including one "explant", which appears to be the opposite of an "implant".
Dijkima HE, Weil EHJ, Mijs PT et al (1993) reported on 23 patients implanted, with (again) 83% of them improved at least 50%, just like the others. Pad use per day went from 4.5 at baseline to 1.8 per day after implant -- not exactly a clinically significant result. Leaks were a little better, from 7.4 to 1.5 leaks a day -- but let's face it, the average patient with a expensive implant was still leaking "once or twice" a day.
The authors are not disturbed by the fact that 3 patients (13%) had an unsuccessful outcome -- in spite of passing the test screening -- and one poor bloke had to have several repeat operations until he was finally classified as "successful".
Finally, Thon WF, Baskin L, et al, in 1991, reported on 57 patients, of which 75% had a 50% or better outcome. (Equivalent to a Burgio score of 37.5% symptom reduction.)
WHO IS THE TARGET?
The Thon & Baskin study raises an important point; who is the target of this intervention? In their website pages and published summaries, Medtronic repeatedly emphasizes that this highly invasive, extremely expensive therapy is intended only for those who are non-responsive to conventional therapies. In public documents, they appear to be sensitive to the AHCPR's Guidelines, which put behavioral therapies first, pharmacologics second, and surgery last, in the sequencing of therapies.
But in the literature published in Urological Journals, "conventional therapies" means only ditropan! It is only necessary to claim that the implanted patients were not successful with PHARMACOLOGICAL treatments in order to justify the expensive implant. None of the urological literature mentions failed attempts at biofeedback -- or even conventional, direct-connect electrical stimulation, for that matter.
One woman on the internet wrote:
I do wish that I had tried vaginal biofeedback before I had done this, but I do believe that I would have eventually come to this treatment anyways. (May 98)
I can't blame her for being "positive" about her implant; she's still in college, and she is going to have to live with this device for another 50 years. Still, it does violate the AHCPR Guideline to implant a person who has never even tried a more effective, less costly alternative.
OFF-LABEL USES
Despite disclaimers, the InterStim literature is ripe with references to off-label uses. [These follow the form "Remember, you are not allowed to eat any of the delicious chocolate chip cookies in the big cookie jar on the kitchen counter".]
One person wrote, for example:
I had problems with urgency and frequency and severe bladder pain. I also had painful periods and severe constipation. I also had severe headaches 3 months before I had this nerve stimulator implanted permanently. I have had a lot of relief with my headaches and bladder symptoms.
She actually reported many more somatic symptoms, but it would make her too identifiable to include them all. Suffice it to say that in real life, implanted stimulators are being used for much more than the FDA has approved.
Another patient wrote to IncontiNet:
I have chronic pelvic pain in association with interstitial cystitis. ... My urologist has suggested that I have the InterStim device implanted, but as I understand it, this has only been approved for the treatment of urge incontinence. Do you have an opinion of the efficacy of the InterStim device for the treatment of pelvic pain? (June, 1998)
In April, 1999, the list was expanded, but it still doesn't include interstitial cystitis -- or vulvodynia, another common suggestion.
MEDICAL DUALISM
One of the persistent problems in dealing with incontinence is the underlying "medical dualism" of many practitioners. "Medical Dualism", or "MD", refers to the tendency to treat all symptoms as EITHER (1) Organic in origin or (2) Psychogenic in origin. The former are the province of urologists, while the later belong to psychiatry. There is no concept of "psychophysiology".
Thus we find, for instance, Goodwin RJ, Swinn, MJ, and Fowler, CJ (1998) referring to Fowler's 1988 description of
"a syndrome ... in which urinary retention was the predominant feature and electromyography (EMG) of the striated muscle of the urethral sphincter revealed a striking abnormality. ... this abnormality interfered with the ability of the sphincter to relax, resulting in retention.
Note the dualism; the "abnormality" is one "thing", and IT "interfered with" the ability of sphincter to relax, another "thing".
A modern, holistic conception of the body-mind issue would say, in contrast, that the "abnormality" IS the inability of the sphincter to relax. People are supposed to be able to relax their OWN muscles -- in the forehead, in the neck, and EVEN in the pelvis. There is only one "thing".
Some people want to find an organic cause for every problem, even when there isn't one. This is commonly called the "medicalization" of contemporary culture.
Medtronic's summary of Goodwin et al goes on to say:
"Until recently, there was no effective treatment [of retention] except management by clean intermittent self-catheterization."
Despite Medtronic's own sorties into the biofeedback field in the late 1980s, their present staff is apparently unaware of the field of Biofeedback, which recently celebrated its 31st Annual Convention.
For over three decades, biofeedback practitioners have been teaching people how to RELAX various striated muscles using electromyographic biofeedback. The treatment of urinary retention is one of the oldest applications in the literature, and has been highly successful since at least 1983. To pretend otherwise is simply dishonest. Isn't someone in Washington supposed to be "regulating" these folks?
BUT IS IT SAFE?
No discussion of implanted electrical stimulation devices would be complete without mentioning the issue of side effects and complications. In all, the 581 initial patients mentioned above underwent 914 test stimulation procedures to see if they would respond. That's an average of 1.6 surgeries each.
A total of 181 "adverse events" (20% of the tests) occurred in 166 (18.2%) of the procedures. In 108 cases (11.8%) the leads "migrated" or moved from where they were supposed to be. (In 6 cases the migration resulted in foot or leg movement instead of bladder inhibition! "Sorry, I didn't mean to kick you; it's my bladder stimulator acting up again!")
Amazingly, Medtronics admits that the "overall surgical revision rate was 33% (73 of 219 patients)." Still, they claim that there were no reports of "serious adverse device effects or permanent injury" associated with the device.
Well, as they used to say back in Vermont, "It all depends whose ox is being gored." When the surgeon says "This isn't going to hurt", I always want to know of whom he is speaking.
It is sad to see that a great company (Medtronic) who pioneered a marvelous device (cardiac pacemaker) has now found it necessary to move into urinary incontinence. The bottom line is that the cost-risk- benefit analysis is entirely different when we are comparing urinary urgency with cardiac arrhythmias, but this difference seems to be lost on the corporate giants of the Medical-Industrial Complex.
PS: WE do NOT send these articles to the FDA. If they want to find out what's going on in the real world, they can join our mailing list like everyone else.
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