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...as a patient it is perfectly ethical for you to act with self-interest as your primary focus.


...it clearly is ethical for you to drop out of a study at any time for any reason or for no reason.


The general principle...is to escalate slowly.

The Patient's Responsibilities


The following excerpt is taken from Chapter 3 of Cancer Clinical Trials: Experimental Treatments & How They Can Help You by Robert Finn, copyright 1999 by O'Reilly & Associates, Inc. For book orders/information, call (800) 998-9938. Permission is granted to print and distribute this excerpt for noncommercial use as long as the above source is included. The information in this article is meant to educate and should not be used as an alternative for professional medical care.

As a culture we value altruism, many of our heroes practice self-denial, and we regard selfishness as suspect. Therefore it's important to state that as a patient it is perfectly ethical for you to act with self-interest as your primary focus. You shouldn't be ashamed of searching out the best possible treatment or the most promising clinical trial. And you shouldn't be embarrassed to ask question after question in your effort to decide what's best to do in what may well be a life-threatening situation.

But how far does the ethical imperative toward personal survival go? Would it be permissible to lie in order to get into a trial, or to use deception to get into the preferred arm of a trial? Is it wrong to have unrealistic hope? Is there an actual ethical obligation for people with cancer to participate in clinical trials? These are difficult questions, and the answers aren't always clear cut. Let's examine several scenarios and discuss their ethical implications. We obviously can't bring up every possible situation here. Think carefully about any ethical dilemmas that present themselves during the course of your cancer treatment. Discuss them with trusted friends, relatives, and spiritual advisors. Many hospitals have experts in bioethics available for advice and consultation on these matters. And remember that reasonable, honorable, and ethical people often arrive at differing solutions to ethical problems. It's not always easy to know what's right.

Scenario 1: Fudging the criteria

Let's say that you have cancer and you've identified a clinical trial that seems perfect, that's testing an exciting new treatment that you are convinced may well lead to a cure. But let's say that you don't quite meet the inclusion criteria. Perhaps one of your lab results is just slightly worse than the acceptable values. Is it permissible for you to lie about those lab results, or to have your personal physician lie to the investigator about them?

Dr. Vanderpool says that it's not permissible to lie in this situation.

"It undermines the entire research enterprise. You could damn an entire line of research by doing that."
That's because a treatment that is actually effective on people who are moderately ill might be ineffective on people who are more seriously ill. If enough seriously ill people mask the severity of their condition in order to sneak into the trial, the treatment may seem less effective than it really is. It might be abandoned even though many people could have been helped by it. Since your deception could potentially deny an effective treatment to many others, it would be unethical to lie in this situation.

Scenario 2: Re-rolling the dice

If you were randomized into the standard-treatment arm of a clinical trial, and you desperately wanted to receive the study medication, would it be ethical for you to drop out of the study at one location and use deception to enter the study at another in an effort to get a more favorable roll of the dice?

First of all, you should recognize that you may be mistaken about whether it would be better to receive the study medication. Clinical trials are conducted in order to figure out whether the study medication is better than the standard treatment. If the scientists already knew the answer to that question, there'd be no reason to conduct the trial.

Second, it clearly is ethical for you to drop out of a study at any time for any reason or for no reason. That's a right guaranteed to you in every document related to clinical trials, from the Nuremberg Code to the Belmont Report to federal regulations, and it is mentioned explicitly in every informed consent document.

But Dr. Vanderpool says that it would not be ethical for you to lie in order to get into the trial at another location. On the other hand, he says, you are under no obligation to tell the whole truth. If someone at the second site asks you whether you have ever been in a clinical trial before, you must answer honestly, revealing that you had been in this same trial at a different location, and that you had dropped out. However, when you are asked why you dropped out, Dr. Vanderpool says that you wouldn't have to give all the reasons. You could just say something like, "I was just going through a time where I didn't want to continue in that trial, but upon second thought I do want to get on it, and I have every expectation I'll stay."

It might be argued that re-rolling the dice like this might de-randomize the study. Patients with more aggressive personality traits, or ones more willing to take risks, might tend to accumulate in certain arms of the trial. But Dr. Vanderpool does not think that this theoretical possibility presents an actual ethical problem. Randomization criteria typically depend on physical and not psychological traits. Psychological traits would only enter the equation if, for example, the patient had clinical depression for which he was taking medication. Moreover, it's up to the investigators to control the entry criteria so that their trial will be acceptably randomized. On top of that, there's no evidence that leaving and re-entering trials is a widespread practice. In fact, while researching this book we were unable to identify a single patient willing to admit that he had tried this technique, or a single investigator who knew of such an occurrence.

Scenario 3: Risky behavior

Let's assume that you have a type of cancer for which there is no good standard treatment, and the only clinical trial you can find is a Phase I trial. Phase I trials can be risky and are not even intended to determine whether the experimental treatment works. They're only intended to determine how toxic it is, and what the maximally tolerated dose would be.

If the investigators have been completely honest with you, as of course they should be, they would inform you that this trial had little chance of leading to a cure for you personally. In fact, studies show that only 4 to 6 percent of people enrolled in Phase I cancer trials show any response at all, and of course far fewer achieve complete remission. However, despite those dismal odds, of the Phase I participants who were surveyed, 100 percent said they participated because of the possibility of benefit, 89 percent said it was because of the lack of a better option, 70 percent cited trust in their oncologist, and only 33 percent mentioned the possibility that their participation would help future patients.

The ethical question that emerges from these figures is this: is it wrong for a person to participate in a Phase I trial while underestimating the risks and overestimating the possibility of personal benefit? Dr. Vanderpool says,

I think patients should have the right to go into a protocol even if they don't stand to benefit. They should be able to try long shots like entering Phase I protocols, where there's little therapeutic possibility. On the other hand, I can honestly say that when I'm in that situation I'm going to scrutinize whether research is my grounds for hope, or whether going fishing or taking the time to make things right with my family and getting palliative care is not a better grounds for hope. There are certainly grounds for hope outside of the doctors' purview and research protocols.

Scenario 4: An obligation to serve?

Some bioethicists believe that we may actually have an ethical duty to participate in clinical trials. The argument goes that since as members of society we have all benefitted by the sacrifices of those who have participated in clinical trials in the past, we all owe it to future generations to participate in clinical trials ourselves.

Most ethicists would not agree with the strongest form of that argument. After all, they say, you can't be expected to incur obligations as part of a social group if you never consented to become part of that group. Suppose you lived in a high-crime area, and some of your neighbors formed a block patrol. They couldn't force you to participate in the patrol even though you are receiving the benefits of the patrol. You didn't choose to receive those benefits so you incur no duty.

But bioethicist Arthur L. Caplan argues that if you choose to receive medical care at a research hospital--presumably because you desire the best, most advanced treatment available--you may then incur an ethical obligation to serve as a research subject. After all, most patients in research hospitals are presumed to have an obligation to serve as subjects for teaching purposes. Your physician will often bring along medical students, interns, or residents to participate in your examination, diagnosis, and treatment. Caplan argues that when you willingly go to a research hospital you have consented to being part of a certain social cooperative, so you do incur a duty to serve. He adds that this is a general obligation, and that you would have no duty to serve as a subject in any specific clinical trial. Informed consent would still apply, and you wouldn't be compelled to participate in studies that pose significant risks.

Caplan's view is apparently not held by a majority of bioethicists, so you needn't fear being forced to participate in a clinical trial merely by choosing to receive care at an academic medical center. Dr. Vanderpool offers his opinion:

Insofar as we and our loved ones will have received therapeutic benefit thanks to research in the past, there should be some sense of responsibility for participating. But I think it's faulty to put that in the form of an ethical obligation. I think the philosopher Immanuel Kant was correct when he said that acts of beneficence are "imperfect duties." A "perfect duty" is something that you should always do, but an "imperfect duty" is something about which you make a judgement call, and whether to benefit others is that judgement call. It's true that I should benefit others, but how much I should do this and how much self-sacrifice I should show is subject to all kinds of considerations. So I think it's very problematic to obligate patients who are sick with cancer to go onto clinical trials.
Dr. Vanderpool suggests that you weigh the argument about obligation and duty along with all the other factors you'll be considering while making your decision about whether to participate in a clinical trial.

How to complain

If you're having any kind of problem with any aspect of a clinical trial, you should first try to resolve it by speaking with the trial's clinical research coordinator (CRC) or the investigator. Only in the unlikely event that they are unable to resolve the problem should you take a complaint to higher levels.

The general principle you should follow in complaining is to escalate slowly. Don't go straight to the head of a federal agency, because problems can often be resolved at the local level, and a resolution at that level is likely to be concluded far more quickly than if you make it a federal case.

If the investigator or her CRC can't solve the problem, go to the local Institutional Review Board. Sometimes the IRB will be a committee within the medical center hosting the trial, but sometimes the medical center or a pharmaceutical company will contract with a private IRB that may not even be located in the same city. Often you'll be able to find the IRB's telephone number on your informed consent document. If it's not there, ask the investigator for the phone number. Ask to speak with the chairperson of the IRB. Outline your complaint calmly and completely. Be clear about how you hope to have the complaint resolved.

When the trial is a multicenter trial, there will be one chief investigator for the whole trial, perhaps at a different institution from the one where you're receiving treatment. In the rare instance where you're unable to resolve your complaint at the local level, you can take it to the study's chief investigator. Another alternative for studies sponsored by pharmaceutical companies is to complain to the director of research at that company. You should be able to obtain contact information for the chief investigator or the director of research from the investigator at your institution or the local IRB. Sometimes merely requesting that information will be enough to underscore how serious you regard the issue, and will encourage the local investigator to resolve the problem.

If these techniques don't work, your next step should be to contact the Office for Protection from Research Risks (OPRR), which is part of the US Department of Health and Human Services. Although the OPRR is administratively part of the National Institutes of Health (NIH), it has jurisdiction over all clinical trials in the US, even those that are not sponsored by the NIH and its member institutes. The OPRR is responsible for administering the regulations in the Code of Federal Regulations, Title 45, Part 46, Protection of Human Subjects. The OPRR maintains an informative web site at: http://www.nih.gov:80/grants/oprr/oprr.htm

It's wise to submit any complaints to OPRR in writing, although they accept telephone calls as well. When writing be sure to specify the nature of your inquiry (e.g., general guidance on policy or allegations of noncompliance) and the nature of the research activity (e.g., a single-center trial, a multicenter trial, etc.). Specify the name of the trial, the investigator's name, and if it's a multicenter trial, name the particular Cooperative Oncology Group (COG) or Community Clinical Oncology Program (CCOP) that's administering it. The OPRR requests that you write the appropriate acronym in the lower left of the envelope (e.g., Re: COG or Re: CCOP if it's a multicenter trial, or the name of the state in which the research is taking place if it's a single-center trial). This allows the office staff to quickly route your inquiry to the appropriate person. Mail the complaint to:

National Institutes of Health Office for Protection from Research Risks
Division of Human Subject Protections
6100 Executive Boulevard, Suite 3B01 (MSC 7507)
Rockville, MD 20892-7507
Phone: (301) 496-7041
Fax: (301) 402-0527
If your problem is primarily with a pharmaceutical company, another place to complain would be the Food and Drug Administration (FDA). The first step is to contact one of the FDA's Consumer Complaint Coordinators. There's a Consumer Complaint Coordinator in every state, and in some large states there are more than one. You'll find a complete list of their phone numbers at: http://www.fda.gov/opacom/backgrounders/problem.html. If you still can't get satisfaction, contact James C. Morrison, the ombudsman for the FDA's Center for Drug Evaluation and Research (CDER):
CDER Ombudsman (HFD-1)
5600 Fishers Lane
Rockville, MD 20857
Phone: (301) 594-5443
Fax: (301) 827-4312
Email: morrisonj@cder.fda.gov
Web: http://www.fda.gov/cder/ombud.htm

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