Saturday, October 13, 2007

Some Thoughts on Clinical Trials and Patients' Rights

I just finished reading an article from Reason, a Libertarian magazine. The article, "Dying for Lifesaving Drugs: Will desperate patients destroy the pharmaceutical system that produces tomorrow's treatment?" by Kerry Howley, discusses patients' rights to experimental drugs versus the FDA's need for proper double blind clinical trials. I found the article's analysis on the necessity of double-blind studies and patient right to be worthy of comment.

The article focuses on cancer patients who, in the course of their treatment, run out of effective methods with which to combat their ailment. These patients are often desperate to try any treatment with the slightest hint of effectiveness because the amount of time spent on ineffective treatments has left them with little time to wait for new FDA approved remedies. The reason is not always how long they have left to live, but more often, it is how long it takes for a treatment to be approved.

The United States has one of the strictest protocols when it comes to testing and approving new medical treatments. Blind and double blind tests are conducted in three mandatory phases. The FDA describes these phases:

"Phase 1 trials try to determine dosing, document how a drug is metabolized and excreted, and identify acute side effects. Usually, a small number of healthy volunteers (between 20 and 80) are used in Phase 1 trials.

Phase 2 trials include more participants (about 100-300) who have the disease or condition that the product potentially could treat. In Phase 2 trials, researchers seek to gather further safety data and preliminary evidence of the drug's beneficial effects (efficacy), and they develop and refine research methods for future trials with this drug. If the Phase 2 trials indicate that the drug may be effective--and the risks are considered acceptable, given the observed efficacy and the severity of the disease--the drug moves to Phase 3.

In Phase 3 trials, the drug is studied in a larger number of people with the disease (approximately 1,000-3,000). This phase further tests the product's effectiveness, monitors side effects, and, in some cases, compares the product's effects to a standard treatment, if one is already available. As more and more participants are tested over longer periods of time, the less common side effects are more likely to be revealed.

Sometimes, Phase 4 trials are conducted after a product is already approved and on the market to find out more about the treatment's long-term risks, benefits, and optimal use, or to test the product in different populations of people, such as children."

It seems obvious that almost everyone would agree that testing drugs and treatments for effectiveness and safety is a good idea, but what happens when a patient has run out of options with approved medicine? Does that patient then have the right to try experiment drugs whether or not the patient qualifies for the clinical trials? It is very often that patients who have "tried everything" are not qualified for clinical trials involving new drugs because the purpose of the trial is to reduce the number of variables in their experiments. It is important that the researchers know that they are seeing the consequences of the new drug in their patients, not the delayed consequences of other treatments.

Okay, so these patients cannot be part of the clinical trials but why not just give them the drug anyway on the off chance that it helps? Surely they can waive their right to sue if it does not help, right? Actually, patients are NOT allowed to waive their right to sue in this case. This is a perceived inconvenience that is currently being contested in the case of Abigail Alliance for Better Access to Developmental Drugs v. Andrew von Esch­en­bach.

On the surface, it seems like a great idea to give patients access to experimental drugs after it is found that they do not qualify for clinical trials. It seems like the most humane and possible lifesaving solution. In fact, it often seems better than being a test subject. However, there are some reasonable objections to this view.

In the Reason article, it is quoted that only 11% of drugs that enter clinical trials end up accepted by the FDA. This number drops to about 6% for cancer drugs. This means that the patient has a greater than 90% chance of receiving an ineffective or even dangerous drug or treatment (even if the patient received a drug that is later proved effective to treat their ailment, there is no guarantee it would work for him or her specifically). While that percentage might seem high, there is at least SOME hope of getting better. However, the time and money spent on approving, manufacturing, and distributing these experimental treatments could be seen as a waste of hard-to-gather research money and a distraction from the research that would clarify which of there treatments are actually effective.

There is also the risk of patients suffering terrible side effects from experimental drugs. Even if they do not sue, these cases could be used as evidence to block the production of a drug that might be found to be effective after more research. It could be that the experimental drug the patient took was not even responsible for the side effects or a combination of that drug with another treatment that caused the problems, but if the side effects were bad enough, it probably would not matter how they arose.

In many clinical trials, only a fraction of the subjects are given the medication or treatment being studied. This is essential to a proper double-blind study. It is imperative that neither the doctors nor the patients know whether they have been given the drug or treatments (an independent group should randomly assign the treatments). This is to help get rid of certain biases in the study, including those of the researchers, and to take into account the placebo effect.

If patients are allowed to take these experimental drugs when ineligible for a clinical trial, it is by no means inconceivable that many patients and their primary physicians might opt to make the patient ineligible for the study (possibly by prescribing a drug or procedure not allowed by the clinical trial) to ensure that the patient is actually able to take the drug and does not end up as part of a control group in the clinical test. For many conditions (certain types of cancer for example), the number of people affected is very small. That means, in order to perform a proper study of a treatment or a drug, a large percentage of the people who are suffering from the ailment need to be available for a clinical trial. It is possible that allowing patients the option of taking experiment drugs could decrease the pool of qualified test subjects. This would slow down the regulation of new treatments and would most likely end some of the smaller studies.

In the end, I believe that the question underneath the issue of a patient's right to take an experimental treatment is whether the possibility of saving one or several lives in the present outweighs the need to conduct clinical trial, in the same manner that they are done today, so more lives are saved in the future. While I agree that allowing patients unchallenged access to experimental treatments is probably a bad thing for the reasons stated above, I cannot in good conscience deny someone their right to seek the means to continue living. Perhaps there are enough people willing to take the risk of a clinical trial to keep the system working and to allow patients who do not qualify to partake in experimental treatments. Sadly, I do not think this is the case. I do not blame those who would rather be guaranteed a treatment than have the chance of ending up part of a control group. We should all be thankful that there are those who are willing to act as guinea pigs for the advancement of medicine.


Flavin said...

I pretty much agree. Clinical trials exist for a reason. If drugs could be administered before trials finished, the number of people who may be helped by an effective drug that hasn't yet passed all its trials is dwarfed by the number who would be hurt by all the other non-effective or harmful drugs that never pass trials.

Re the Abigail Alliance trial, denialism blog has a post about a WSJ article on that case.

Ben said...

I believe there is a case for drugs which have already passed certain phases of clinical trials, but I do not know how to ensure that the current system is not undermined by giving patients access to unapproved pharmaceuticals. There must be a way to allow patients with no other options at least to have the chance to take these drugs. Perhaps after a certain amount of testing, drugs could be approved for a sort of last resort treatment, but I am still afraid that any negative side effects might have detrimental effects on the study.