This is Why No One Trusts the Pharmaceutical Industry: GlaxoSmithKline’s employee ambassadors are going to have a hard time convincing anyone who reads this Wall Street Journal front pager that the pharmaceutical industry deserves a better reputation.
The Journal reports on a new blood substitute developed by Northfield Laboratories. In a recent clinical trial, 10 of 81 patients who received the fake blood suffered a heart attack within seven days. Nevertheless, the company and the FDA have decided to push ahead with clinical trials. I don’t have a problem with that. If experts believe this a promising new treatment, it should be tested.
What I have a problem with is that way the company is going about it. The company will not seek the consent of patients before treating them with the experimental blood (many of them are unconscious at the time, although that doesn’t mean their family or loved ones could not be asked for their consent).
Even worse, according to the Journal: “In lieu of patient consent, the 31 medical centers testing the product are required to carry out community-awareness campaigns about the trials. Several hospitals have told community meetings that previous trials showed PolyHeme to be safe, failing to mention the 10 heart attacks in their printed materials.”
This is, in other words, the very opposite of informed consent: it is misinformed non-consent. And it is completely indefensible.
That doesn’t mean the company won’t try. The Journal quotes Northfield CEO, Steven Gould: “Our experience suggests the risk-benefit balance is in the patient’s favor.”
That may very well be true… but it’s not the company’s decision to make. Guidant made a similar defense over faulty defibrillators. It’s a defense that suggests the company patients to trust a large, not-entirely disinterested corporation to make health decisions for them. Worse, that same company doesn’t trust them with the information they need to make the decision themselves.
The final twist: “Northfield says any American who doesn’t wish to participate in the current PolyHeme trial should ask the company for a blue plastic wristband that would alert paramedics.” In other words, any patient who has read The Wall Street Journal story, and ignores the company’s own evasive “community outreach” and is therefore well-informed enough to opt out can do so.
This kind of behavior makes consumers skeptical about the entire industry. And that fact this behavior is permitted by the FDA undermines confidence in regulatory mechanisms that ought to be the foundation of trust in the industry.
The Journal reports on a new blood substitute developed by Northfield Laboratories. In a recent clinical trial, 10 of 81 patients who received the fake blood suffered a heart attack within seven days. Nevertheless, the company and the FDA have decided to push ahead with clinical trials. I don’t have a problem with that. If experts believe this a promising new treatment, it should be tested.
What I have a problem with is that way the company is going about it. The company will not seek the consent of patients before treating them with the experimental blood (many of them are unconscious at the time, although that doesn’t mean their family or loved ones could not be asked for their consent).
Even worse, according to the Journal: “In lieu of patient consent, the 31 medical centers testing the product are required to carry out community-awareness campaigns about the trials. Several hospitals have told community meetings that previous trials showed PolyHeme to be safe, failing to mention the 10 heart attacks in their printed materials.”
This is, in other words, the very opposite of informed consent: it is misinformed non-consent. And it is completely indefensible.
That doesn’t mean the company won’t try. The Journal quotes Northfield CEO, Steven Gould: “Our experience suggests the risk-benefit balance is in the patient’s favor.”
That may very well be true… but it’s not the company’s decision to make. Guidant made a similar defense over faulty defibrillators. It’s a defense that suggests the company patients to trust a large, not-entirely disinterested corporation to make health decisions for them. Worse, that same company doesn’t trust them with the information they need to make the decision themselves.
The final twist: “Northfield says any American who doesn’t wish to participate in the current PolyHeme trial should ask the company for a blue plastic wristband that would alert paramedics.” In other words, any patient who has read The Wall Street Journal story, and ignores the company’s own evasive “community outreach” and is therefore well-informed enough to opt out can do so.
This kind of behavior makes consumers skeptical about the entire industry. And that fact this behavior is permitted by the FDA undermines confidence in regulatory mechanisms that ought to be the foundation of trust in the industry.
posted by Paul A. Holmes @ 12:35 PM
10 Comments:
At 5:55 AM,
Anonymous said…
Mr. Holmes, it seems as if you have taken the bait laid out in the Wall Street Journal and through willful act or ignorance have not only perpetuated but have compounded some of the key misleading points therein.
Careful reading will show that the trial involved with the heart attacks was not recent, but was almost ten years ago. That trial involved consenting patients undergoing a planned surgical procedure. The company involved, the surgeons involved, and the FDA concur that the blood substitute was NOT responsible for the cardiac problems.
The current trial on trauma patients is consistent with FDA policy and regulation, utilized only a half dozen times I believe, where it is recognized that certain products with a very high life saving potential can only be tested on those at least temporarily unable to give an informed consent. In fact, the FDA participated in the design of the trial. The patient or his family may halt the participation at any time during treatment and follow-up.
To date, over 600 patients have been enrolled of a planned total of 720 in the current trial with half receiving the product in question, Polyheme, and the other half receiving the current standard of care. That care consists of intravenous saline solution until such time as the bleeding victim has been transported to a hospital, had his blood typed, and can begin to receive transfused blood.
The problem with that is "the golden hour" oft mentioned to receive critical treatment is frequently lost. Saline does not carry oxygen to the body's organs and they may begin to shut down. The new product, derived from human hemoglobin simply adds critical oxygen carrying ability to a solution similar to saline.
At four intervals during the current trial interim reports have assessed the process, efficacy, and safety of the study. At each juncture, the decision was to go forward with the study unchanged. The thirty some hospitals taking place in this landmark study each have internal review boards monitoring its progress; none have withdrawn. These are not small, community hospitals but are level one trauma centers at some of the nations most highly regarded medical centers including Loyola in Chicago, Hermann Hospital in Houston, Denver Medical Center, and the Mayo Clinic.
Perhaps some further research is in order before trashing an endeavor that may help to change the way the seriously injured are treated. Reductions in multiple organ failure, and inevitably, trauma related death may be on the horizon.
Your concerns relating to consent do not fall on deaf ears, but unless you are armed with all the pertinent facts, not just those chosen to be included in one writer's work you do a disservice to the trial process. If you can devise a more efficient way of testing such a product I'm sure both Northfield Laboratories and the FDA would be open to your suggestions. Just saying "no" doesn't cut it.
At 6:31 AM,
Paul A. Holmes said…
This comment has been removed by a blog administrator.
At 6:50 AM,
Paul A. Holmes said…
You say: "The company involved, the surgeons involved, and the FDA concur that the blood substitute was NOT responsible for the cardiac problems."
All the more reason, it seems to me, for the principle of informed consent to be applied here. If that's the case, share the information with the community... It's this notion that "we experts, we authorities" are going to take this decision out of people's hands that comes across as cynical. "Trust us, even though we don't trust you to make the 'right' decision with the information."
As for a better way to proceed, if the first trial could be conducted on people who gave their consent, I'm not sure why that was not a viable option for continuing trials, especially if you want to extend that to family members giving consent. I understand this might delay the approval process, but if it has been 10 years since the first trial, why suddenly so impatient?
At 5:46 PM,
Anonymous said…
Perhaps you do not understand the concept of a trauma trial. When a gunshot victim is lying in a stairwell, a motorist is trapped in an overturned car, or a shopper has run through a plate glass window and they are all pumping their very life onto the ground shall we never attempt to find a substance that will continue to carry oxygen to their vital organs because they can't sign a proper document or their next of kin can't be reached?
Would it make you feel better if we just continued to pump saline in one hole and out the other until their brains shut down? How long does it take that first EMT to get to the scene? How long to extricate the victim from a destroyed vehicle? How long after that will they be in a hospital finally getting their blood typed so they may eventually receive blood? In far too many cases, far too long.
Jehovah's Witnesses who refuse blood transfusions have received Polyheme and it has saved their lives. Patients have had 20 units of Polyheme put through their bodies while the body holds only ten. Organ failures and serious side effects from blood transfusions have been reduced or eliminated; Polyheme does not support the transmission of disease as does blood.
But these are not the type of episodes upon which a scientific trial can be run. Controls must be established and it was largely a problem with using historical evidence as a control group that caused the earlier tests to be abandoned.
Only half the people in the current trial will receive Polyheme, the remainder will receive the current standard of care as a control group. In doing so, half the trial population is at risk of bleeding to death because they can not now receive Polyheme. How long should we wait until they can?
There are about thirty small geographical areas within the USA taking part in this trial. In each area the hospital and other agencies have held meetings and issued public service announcements informing their constituencies of the test and offering an exclusion option to anyone not wishing to take part.
FDA regulations allow for a waiver of informed consent process in extremely rare cases where consent would be impossible. This is one of those cases.
Mr Holmes, I trust you have done some research regarding this trial and I ask you if you or a loved one were trapped in an overturned car thirty miles from the nearest hospital with one or more limbs severed would you want the EMTs to immediately take whatever steps necessary to save your life or should they go through your belongings in an attempt to find someone with the legal authority to authorize just that. Remember, right now, without your consent, they will infuse your bloodstream with salt water. Good luck.
At 7:39 AM,
Paul A. Holmes said…
At this point, I can't help wondering if you're deliberately misreading my post. At no point have I suggested that these trials should be stopped.
What I object to is a policy of deliberately misleading the public. If the community outreach program omits facts about the heart attacks that occurred in the earlier trial, it denies patients or prospective patients information to which they are clearly and absolutely morally entitled.
You have demonstrated in these posts that it is possible to present the risk-benefit information in a coherent way so that people could make an informed choice, and I suspect many of them-- me included -- would make the choice to accept the risk. If you are capable of making that argument, surely the company's professional communications staff should be too?
Yet the company has apparently decided it's just too much hard work to supply people with all the facts, and with the context. It seems to think that people are too stupid to make a judgment based on the evidence, and so it has relieved them of the burden of even seeing that evidence. That's just wrong.
At 8:56 PM,
Anonymous said…
THE DENVER POST
December 7, 1999 Tuesday 2D EDITION
Edited - For the full story see http://www.denverpost.com/life/artis1207.htm
SECTION: SCN; Pg. F-01
HEADLINE: Reclaiming a Life CU crash victim beats long odds with rebuilt leg
BYLINE: By Bill Briggs, Denver Post Staff Writer,
BODY:
She won't show you the leg, won't show anyone except her physical therapists, her surgeons and maybe her parents.
And that's a shame really. Because Artis Selby's right thigh is a testament to modern medicine, wild luck and a young woman's blue-steel grit...
...according to witnesses, this is what happened: A flatbed truck, carrying at least 50,000 pounds of steel plates and tailing Selby's Camry, swerved from the left lane into the right, barreling into a Subaru. It literally ground up the Subaru, killing the two newlyweds in that car. The flatbed then broke free and mowed over the top of the Camry, collapsing it into a heap of braided metal. Some parts of Selby's car were never found.
Minutes later, paramedics from the Mountain View Fire Department started dismantling the crushed Camry to free the 19-year-old driver. They faced two critical countdowns: If Selby's leg was going to be saved, blood flow had to be restored in roughly six hours or the tissue would die. Even worse, she was bleeding badly, and if she was to be saved, the bleeding had to be stopped and the blood quickly replaced.
"It was touch and go in the car," says her mother, Linda Cornett. "If she lost consciousness, they were going to cut the leg and go. I know they tried to keep her conscious. I don't think they told her why. The firefighters said she called them every name in the book and said, "Get me out of here!''
It took about three hours to gingerly pull Selby from what was left of the Camry. But this is where a stunning run of good fortune started to kick in. It was cold that day, and doctors say the frigid weather probably slowed the destruction of blood-starved cells in her leg.
A Greeley Flight for Life crew choppered Selby to Denver Health Medical Center, where Smith and a team of limb salvage experts were scrubbed and waiting.
"She was basically out of blood when she got to the hospital," recalls her father, Rollie Selby.
In fact, she had gone into shock. But Selby's good luck continued. Because she needed so many replacement pints so fast, emergency-room medics pumped her full of a synthetic blood called PolyHeme, locally available only at Denver Health. The experimental product is thought to reduce the serious side effects, like internal inflammation, that can come with a full blood transfusion.
"She got a lot," Smith says, "and it worked. It allowed her to be resuscitated. This is one of the only places in the country approved to use PolyHeme because we're part of an FDA study."
At 10:41 PM,
Anonymous said…
Mr. Holmes, in the current trial, the results of prior studies -- including the old trial referred to by the Wall Street Journal (which every site was informed of) -- have been shared in advance of using Polyheme by leading trauma centers through community meetings and other means. Furthermore, in every center area the public can get a bracelet to wear forbidding use of Polyheme if there is no one available to make such a decision, if they are unable to do so.
Two examples of (uniform) community information are given below:
SALT LAKE CITY
From the Salt Lake City Hospitals community meetings in June, 2005, the ANH study was referenced. Here is an excerpt from the SLC material:
What has been the safety experience with PolyHeme® in prior studies?
During the course of evaluation of any investigational product, both adverse experiences and serious adverse experiences can occur. These may be due to either the underlying condition of the patient, the treatment setting, or the investigational product itself. Both adverse experiences and serious adverse experiences have occurred in prior studies.
PolyHeme® was studied in one trial in patients experiencing planned acute blood loss while undergoing elective surgery for abdominal aortic aneurysm. The trial included a non-routine procedure called acute normovolemic hemodilution (ANH) in which a large quantity of the patient's own blood, up to 60%, is removed prior to the surgery, and is later replaced. The procedure in this study resulted in the infusion of large volumes of blood in addition to up to 6 units of PolyHeme® in the experimental group, while smaller overall volumes of blood alone were administered in the control group. Serious cardiovascular adverse experiences occurred more frequently in the PolyHeme® group. The patients in this study were older with more cardiovascular risk factors than those in the trials in trauma patients. It cannot be determined whether these findings are due to the more extensive ANH in the PolyHeme® group, to the reinfusion of more blood following surgery in the PolyHeme® group or to PolyHeme® itself.
KANSAS CITY:
As disclosed from the KU Polyheme FAQ's.
PolyHeme® was studied in one trial in patients experiencing planned acute blood loss while undergoing elective surgery for abdominal aortic aneurysm. The trial included a non-routine procedure called acute normovolemic hemodilution (ANH) in which a large quantity of the patient's own blood, up to 60%, is removed prior to the surgery, and is later replaced. The procedure in this study resulted in the infusion of large volumes of blood in addition to up to 6 units of PolyHeme® in the experimental group, while smaller overall volumes of blood alone were administered in the control group. Serious cardiovascular adverse experiences occurred more frequently in the PolyHeme® group. The patients in this study were older with more cardiovascular risk factors than those in the trials in trauma patients. It cannot be determined whether these findings are due to the more extensive ANH in the PolyHeme® group, to the reinfusion of more blood following surgery in the PolyHeme® group or to PolyHeme® itself.
Possibly there is a problem here in relying on the Wall Street Journal for accuracy, as the Company noted in its comment on the article.
At 1:58 AM,
Anonymous said…
I am not the same anonymous as the prior poster or posters. However, anonymous's posts are compelling.
Unfortunately, Mr Holmes, you seem to be caught up in the angry, self-righteous anti-pharmaceutical company mood that prefers to see the world in black and white. The problem with basing self-righteous outrage on a newspaper article is that the articles are frequently pandering to your self-righteousness, and you do yourself and others a significant disservice by not doing your own careful research before publishing in a public forum. Given your prior position, have the anonymous posts changed your mind at all?
At 8:02 AM,
Anonymous said…
Mr. Holmes
You just don't get it, do you??
Sudden severe trauma with life threatening hemorrhage is the basis for the current Northfield clinical trial testing their revolutionary product, PolyHeme.
The patients qualifying for treatment are literaly "bleeding to death." They need treatment...NOW!!! Most are COMPLETELY INCAPABLE of giving full "informed consent."
Medical professionals, the FDA and the prestigious trauma centers that asked to participate all fully comprehend this fact.
Moral and ethical objections along your lines were raised in North Carolina, but the Duke Medical Center fully squared all the objections from dissidents and Duke was allowed to proceed with their participation. In fact, unlike yourself, they weren't duped by the WSJ article and have already PUBLICALLY announced that they will happily continue with the trial.
Your initial blog was inflammmatory and does not serve the public well. A more in depth review of the history of NFLD/PolyHeme might have encouraged you to SUPPORT Northfield rather than hint darkly that Northfield was somehow taking advantage of injured patients.
In fact, it is my professional medical opinion that it would be better for YOU to receive PolyHeme rather than salt water in a trauma in which you were not able to give your own consent.
At 9:39 AM,
Paul A. Holmes said…
So many interesting points raised in these comments, rather than responding to them here I thought I'd put all my thoughts together in a new post, and open the discussion back up to everyone there.
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