Clinical Trials, Patient Harm And Lawsuits
6 CommentsBy Ed Silverman // January 31st, 2008 // 8:43 am
Just what can happen when a clinical trial goes awry and a participant is hurt? Take the example of Suzanne Davenport. The Wall Street Journal chronicles how she entered a trial testing a drug for Parkinson’s disease - before the trial, she could drive, cook and care for herself. Within months, she was in a wheelchair in a nursing home. Her family says the trial caused her precipitous decline and, faced with growing medical bills, filed a lawsuit againt the two drugmakers that ran the trial and the university that enrolled her in the trial.
The case highlights one aspect of the legal and regulatory void surrounding clinical trials, the Journal points out. That’s because federal law doesn’t require researchers to compensate participants harmed in trials - they’re only required on their consent forms to spell out whether compensation will be available for research-related injuries in trials that involve more than minimal risk.
The prospect of compensation for injuries can encourage volunteers who might otherwise be reluctant, the paper continues, but adds that wording in consent forms can be confusing or vague. For instance, it may be unclear which research entity is responsible for the cost of subsequent care, how much that entity will pay and under what circumstances it is obligated to pay, the Journal writes.
One big problem is that it can be difficult to separate what was caused directly by a trial from the natural progression of a participant’s disease. Drugmakers “do not want to end up paying for all of somebody’s care when that care may simply be the product of the fact that that person had a grave illness,” Haavi Morreim, a University of Tennessee bioethics professor who has studied clinical-trials lawsuits, tells the Journal. We raised this issue recently concerning omissions in consent forms for Merck’s Vioxx trials, which you can read about here.
The issue is gaining attention as drugmakers face increasing financial pressure to develop new meds and so are conducting more clinical trials. World-wide, the number of industry trials rose to 59,000 in 2006 from 40,000 in 2000, according to an estimate from CenterWatch, the Journal writes.
You can read the rest of the story here, but a subscription may be required. [Make sure to take a look at the documents. For instance, there are links to the university consent form signed by Davenport; the contract between the university and the drugmaker; the consent form prior to her surgery, and a series of exchanges between her daughter, the drugmaker and the family attorney.]
ol cranky
Ed:
You have to be a WSJ subscriber to read the whole article. Are the links you reference available to non subsribers? I’d be very curious to review them.
I have to say, I’ve never had the experience of a company refusing to pay for treatment of an adverse drug reaction (ADR) and have known companies to just settle when the adverse event could not have been related to study participation or a study drug (i.e., an MI suffered during the “run-in” period of a trial of a cardiovascular indication; run-in periods are to get baseline so the subject’s current treatment regimen is not altered in any way). This being said, I haven’t had the experience of an ADR causing such a quick decompensation of a degenerative disease (and I’ve worked on PD) where you have to evaluate progression of disease vs ADR.
In my years working on trials, I had a patient who wanted the site or drug company to pay for treatment of a broken leg (injury due to his wife’s very bad driving). I also had the sponsor reimburse a patient for emergency room treatment and follow-up care (basically a prednisone burst and some spirometry) of a patient who suffered an asthma exacerbation that was most definitely related to the study drug which, ironically, was for the treatment of asthma and development of the drug was discontinued.
Most Informed consent forms have an injury statement similar to the following:
If you experience any side effect or injury, notify your study doctor right away so that you can be treated.
If you suffer any adverse reaction or other injury because of the study medication, SPONSOR will cover the reasonable costs of medical treatment if:
- You take the study drug as instructed by your study doctor (this is removed if the drug is administered only at the study center)
- Your injury is not caused on purpose
- You tell study doctor about your injury right away
- You follow the medical advice of the study doctor
You will not be paid for lost wages or other damages or losses *or for medical expenses that are covered by your medical or hospital insurance or by third-party or governmental programs providing such coverage*(language between asterisks is almost always removed; pharma lawyers require it in the ICF template, but the IRBs don’t accept it and I’ve always been allowed to remove it). No other form of compensation is available except remedies available under the law. Payment for medical expenses is not an admission of fault or liability by SPONSOR or anyone else.
ol cranky
Oops, I just realized you can access the PDFs from the second link. The injury statement on page 14 looks like the lawyers tried to be creative: “If you are injured as a direct result of research procedures, you will receive treatment at no cost” As written it implies not only that treatment related to such an injury will be gratis and paid for by either the study sponsor and/or UCLA. The reason IRBs require the removal of the reference to 3rd party payments (as noted in my initial post) is because if the injury is a direct result of the study drug/procedure, a third party can refuse to pay for it.
In reality, in a case such as this where the study protocol was amended due to the subject’s injury and it was recognized that the injury was directly related to the procedure, the battle for who pays is between UCLA, Berlex (Schering)/Titan, and the neurosurgical treatment centers directed the Investigator to use.
It would be perfectly reasonable to assume that the decompensation was directly due to the treatment which involved surgical implantation in the brain. This, to me, is more clear cut (pardon the pun) than it would be to assess decompensation that may be due to disease progression of a neurological when treatment doesn’t include an invasive procedure to the brain.
Peter J. Pitts
A far more difficult question (not discussed in the WSJ article) is that of patient therapeutic misperception. Can a patient really make an informed decision about what risks he or she is willing to take in the face of serious disease?
To investigate what patients really understand about the trials in which they have enrolled, leading Parkinson’s Disease researchers, ethicists Kim and Kieburtz, have been awarded a 2007 Michael J. Foundation grant to study ongoing participants of PD clinical trials that involve sham surgery controls. They plan to assess, by structured interviews, the potential for the therapeutic misconception i.e., why and how PD patients make their decisions regarding participation in sham surgery controlled studies
Regardless of the outcome, the biggest question remains the concept of what desperate patients want to understand and what they will do for a glimmer of hope.
Lisa Van S
Peter Pitts
Recently NJ passed a law that an outsider can consent for an Individual to be placed in a clinical Trial. I, as an individual, (personally) is vehemently against participating in a clinical. Peter, who will protect me!!! Who will protect my rights. Integrity in clinical Trials!! Why dont you tell the American People the truth,..PETER. Why dont you tell NJ Residents what you really stand for….HMMMM Pharma Profits
ol cranky
Lisa:
How are the defining who can provide proxy consent and what circumstances - are you sure they weren’t providing guidance around trials of indication involving emergency treatment? I can’t imagine that the NJ law would allow for someone to provide proxy consent to participate when the patient is competent (conscious, oriented, etc.) and/or has available legally authorized representative (LAR). I think there would be another federal preemption case if NJ decided to enact regulations for informed consent to participate clinical trials that were less stringent than CFR.
For trials of indications of non-emergency care, many companies and IRBs allow only a LAR. Some will allow next of kin (if not LAR, then a primary relative who is making other medical decisions) for in-patient studies in which the patient is incompetent to consent. On the occasion that an inpatient is incompetent to consent and no LAR/next of kin is available, proxy consent may be given after review and approval of the hospitals ethics committee/IRB. I’ve always required the investigator to call me for sponsor approval to even broach this consideration with the IRB and only given a waiver to enroll after receiving written documentation of IRB approval and proxy consent; sites were informed that my waiver would require re-consent if/when a family member could be contacted and/or re-consent by the patient if/when the patient was competent to consent (always with additional reminder that they could decline to consent and discontinue study participation immediately). To be honest, I’m not sure if I ever provided a waiver; I know I enrolled one and possibly 2 subjects under these circumstances when I was working at a hospital.
If you are personally concerned that, if you were admitted to a hospital, you would be enrolled in a trial without your consent or the consent of your husband, you could always add a statement to your living will indicating that you should not be enrolled in any clinical trial/medical research of any kind for any reason.
Peter:
I believe, though I could be mistaken on this, that CISCRP is actually trying to find better ways to ensure potential study subjects are truly informed and empowered.
One paradox that I noted working with patients and their families was that the less appealing I made a study appear (i.e. the more skeptical an outlook for benefit I presented) when consenting ICU patients and/or their LAR, the more likely they were to provide consent to participate.
ol cranky
Lisa:
I’ve just reviewed the NJ law you referenced (NJ A-2739/S-1757) and am very relieved to tell you that you were either misinformed about the bill or misunderstood it. What the law does is to further define who, in a non-emergency environment, is able to provide consent when an adult patient is incompetent to do so (and confirm that the patient is incompetent to consent). It also delineates the pecking order of who can consent for an incompetent patient and indicates that when more than one person with the same level of claim of authorization to make decisions have a difference of opinion as to whether consent should be given, the dissenting party’s claim supersedes that of the consenting party.
Rest assured, the law is not in any way inconsistent with US CFR or ICH, so the requirements I sent to you yesterday are 100% applicable. In short you can not and will not (legally) be enrolled in a clinical trial of a non-emergency treatment without your expressed written consent if you are competent to make the decision and your family retains full control over whether to consent to your participation until you are able to make decisions yourself.