Re: Participation in experimental treatments

From: J (auteur_at_anon.invalid)
Date: 03/03/05 

Date: Thu, 03 Mar 2005 04:10:50 -0500

eveline wrote:

> participation in cancer trials offers benefits. People with advanced cancer
> who try experimental treatments are helped more than previously thought,

http://www.cancerguide.org/clinical_trials.html
CancerGuide: Clinical Trials and Experimental Treatments
Clinical trials are conducted within a complex system with fairly well defined
rules. A good understanding of the system gives you a framework for making good
decisions. It also gives you an essential framework for understanding clinical
trial results reported in the medical literature. There are can find brief
superficial explanations of the sytem in many sites. My approach is to give you
a detailed and intensely patient oriented tour specifically designed to help you
find the best treatment.

Understanding the details will help you:

    * Ask the best questions about trials you're considering
    * Know which kind of trial is likely to be appropriate and more quickly weed
out inappropriate trials
    * Recognize promising trials
    * Recognize unpromising trials
    * Give you other options if eligiblity or randomization is making it hard to
get the treatment you want
    * Maximize your odds through strategic thinking

In this article I set the stage with a brief introduction to the system, and
then link you to CancerGuide's detailed Phase by Phase Guides. If you're already
somewhat familiar with clinical trial phases you may want to skip directly to
the detailed guides.
A Few Important Principles

As you go through CancerGuide's clinical trial articles, there are a few general
principles which you'll want to keep in mind which will help you put it all
together.
Promise and Uncertainty

I talk much about things being more or less promising based on the data, but
often you just can't tell. When considering previous results of new treatments
there is almost always great uncertainty. Often the data simply do not exist to
suggest a new approach is truly promising and you may be unable to determine
whether a particular trial is promising or not. Don't expect to be able to come
to a definite conclusion about each and every trial - or even most of them. But
when there are data suggesting there is real promise, and when you find that
data, understand it, and act upon what you find, you may change your odds by
getting the best treatment!

Each Option Must Be Compared to All Others

Although I describe strategies for investigating and thinking about each phase
of trial, in reality, to find the best, any treatment option must be evaluated
in the context of all other options. The alternative to a Phase I trial is not
just another Phase I trial, but any other trials you are qualified for as well
as any standard treatments which might be of value. It is impossible to know if
something is promising unless you know what results can be expected with
standard therapies.
Variations on a Theme

Trials can vary from the standard or classic model, and a surprisingly large
number of trials are non-standard in one way or another. I describe the standard
and some of the variations for each phase of trial, but I can't hope to cover
all of the possiblities. But understanding the standard cases will help you
figure out how to understand and evaluate trials even when they don't quite fit
the classic mold.

The System In a Nutshell
Phase I Trials

    * In a Phase I Trial, the first phase of testing, a new drug or treatment is
tried in humans for the first time ever. The goal of the Phase I trial is not to
see how well a new treatment works but rather just to discover how much of the
drug can be given safely, and to understand its side effects and chemistry in
the body. These trials most closely fit the stereotype of a truly experimental
treatment. Phase I trials are for patients with advanced cancer who have no
effective standard treatment.

Steve's Advice In a Nutshell
The limited experience with the treatment normally makes it extremely difficult
to evaluate the promise of the treatment, and there is a significant risk of
getting an inadequate dose, even if the treatment is effective. Phase I trials
are open to some patients who don't qualify for Phase II trials, and very
carefully selected Phase I trials can be promising, but most patients who
qualify for other trials would be well advised to avoid Phase I trials.

Phase II Trials

    * In a Phase II Trial, the new treatment is tested to see if it can shrink
tumors in patients with a particular type of cancer using the dose and schedule
set during the prior Phase I trial. This is the first test of efficacy. Like
Phase I trials, Phase II trials are for patients with advanced cancer, but Phase
II trials also have some additional entry requirements.

Steve's Advice In a Nutshell
Phase II trials offer the opportunity to get a new treatment at the correct
dose, and without the uncertainties of randomization. The amount of prior
evidence for a treatment in Phase II is highly variable, but can be enough to
suggest the trial is promising. In my judgement if you have advanced cancer,
your greatest chance to benefit from a new treatment through a clinical trial is
probably a Phase II trial, but the trial must be carefully selected.
Phase III Trials

    * In a Phase III Trial, the new treatment is compared to the standard
treatment to see which produces better survival. Phase III trials are normally
randomized - half the patients are randomly selected to get the new treatment,
and half the standard treatment. The survival of the two groups is then compared
to determine which treatment was best. In some cases, Phase III trials compare
two standard treatments or two new treatments. Phase III trials are not limited
to patients with advanced cancer, but may be a consideration at any stage.

Steve's Advice In a Nutshell
Phase III trials are randomized, which means you don't know what treatment you
will get until after you enter and you are randomly assigned to an arm of the
trial. This complicates the decision making! In an ethical Phase III trial, the
evidence shouldn't favor one treatment to the degree that the outcome is a
forgone conclusion, but it is still quite possible that a rational analysis of
the trial in light of your values would conclude that one arm is more desirable.
Phase III trials involve better established treatments than earlier phase trials
and there should be more available evidence on the treatments involved than is
the case for earlier phase trials. Phase III trials can offer the chance for an
improved treatment, but require very careful strategic thinking.

Adjuvant Trials

    * Adjuvant Trials are tests of additional treatment intended to reduce the
risk of recurrence after initial treatment (usually surgery) for apparently
localized disease. Most adjuvant trials are basically a special type of Phase
III trial, and are randomized, but the considerations in choosing one are
different enough that they deserve a separate discussion.

Steve's Advice In a Nutshell
You only get one crack at adjuvant therapy, so you need to investigate adjuvant
trials before starting any standard adjuvant therapy! You also have to enter the
trial within a limited time after completing the primary treatment and sometimes
even before starting the primary treatment, so you must investigate these trials
promptly. Your decision must take into account your risk of recurrence, the side
effects of treatment, whether there is any standard adjuvant treatment, and the
specific evidence for the treatments used in any particular trial.

Regulatory and Institutional Aspects in Brief

Human Subject Protection

Clinical trials are governed by a complex bureaucracy and process designed to
protect people from unethical research. CancerGuide does not dwell on regulatory
protections because I believe that your best protection is to become deeply
informed! But you should know that all reputable clinical trials are approved by
a local Institutional Review Board to ensure that they meet minimum nationally
established ethical standards. This includes ensuring that trials do not
seriously harm patients solely for the purpose of gathering research data, that
the risks are appropriate considering the situation, and that patients who
participate in a trial give their informed consent through a process which
culminates in signing an informed consent document. For advice on how to get the
most out of informed consent, see my article, A Guide to Informed Consent for
The Active Patient
Regulation of Experimental Drugs and Devices

In the US, to use any drug or device that is not approved for general marketing
(e.g. "experimental") researchers must obtain a permit called an IND. An IND is
approval to use an experimental drug usually in a clinical trial, but it does
not mean the FDA has approved the treatment for general use or even that it
thinks the treatment has merit. Occasionally I see drugs or nutritional
supplements touted as "FDA approved" when the only approval is an IND for use in
clinical trials.
Eligiblity Criteria

A notable and important feature of the clinical trial system is the strict and
complex set of eligiblity criteria for each trial. Understanding this aspect of
the system will make it much easier to figure out which trials you qualify for.
The eligiblity criteria are include relatively standard requirements for all
trials as a whole, some requirements which are typical of each phase trial, as
well as many requirements which are specific to a particular trial. I cover the
standard phase specific requirements in my detailed article on each phase of
trial.

Next Steps
Steve's Strategic Clinical Trial Guides: Phase by Phase

(see more) there and...

he goes on to cite a testicular cancer patient, which is germ cell...curable.

Phase I and II also measure for toxicity.

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