Clinical Trials: The Evidence and Where to Find It
I strongly believe in choosing a clinical trial (or any treatment) based on the
prior evidence. This article is a guide to finding that evidence for a
Which Trials to Research
Before plunging into just how to research a trial, it's worth considering which
trials to research. A deep and through investigation of even one trial is a
significant effort. If there are only a few trials of interest you could
research them all, but if you have a large number of trials to choose from, you
aren't going to have the time to get all the evidence for every trial.
Here are a few hints on choosing trials to research:
- If you have a long list of trials, first weed out the ones you don't
- If there are several similar trials, it's worth researching that area of
the medical literature in general to see if there is promising evidence which
is generating interest in that type of treatment.
- Information from your doctors and from networking with other patients may
lead you to promising trials.
- Use these methods to thoroughly research any trial your doctors have
proposed you take part in.
If you still have too many options, you can also do only some of the research
for each trial so you can choose the most promising options for more through
There Will be Some Evidence!
I often hear from patients that they "can't find anything" on some trial or new
drug. But evidence from prior testing exists for every clinical trial! Even
initial phase I trials of new drugs will have prior pre-clinical (animal and
test tube) evidence. Whether you can get your hands on that evidence is another
story, but usually you can get most of it. Both the amount of evidence and its
availability will vary greatly between trials, with generally more evidence
available for later phase trials. Although you are likely to be able to get
your hands on some evidence, it isn't always enough to guess whether the trial
is truly promising or not. Ideally you are looking for a trial where you can
make that judgment. It may not be the first trial you look at!
Searching The Medical Literature
You will usually be able to find a substantial amount of information by
searching for articles in medical journals and presentations at professional
societies, as described in elsewhere in CancerGuide. You'll want to search for
the names of the drugs or treatments used in the trial, and also the names of
the doctors who are conducting the trials.
Special Sources of Information for Clinical Trials
The main focus of this article is to clue you into some important special
sources of information that pertain to clinical trials in progress.
- The Informed Consent Document
Before you start treatment in any trial, you'll sign an Informed Consent
Document. One major advantage of the informed consent is that it's specifically
written to be understandable to patients. The informed consent describes both
risks and possible benefits, but in my experience (and in the great American
tradition of "lawyer warnings"), a great deal more space is devoted to
mentioning every possible risk and side effect than is spent explaining the
history of the treatment or detailing its promise, or to seriously comparing it
to other options. Unfortunately, in the informed consents I've seen, the
information on these critical aspects of the trial is close to useless. If
you've done your homework, you may not find any new information in the informed
consent at all. Still it's worth reading just in case there's something you've
missed. The informed consent should be easy to obtain from any doctor or
research nurse involved in the trial. You shouldn't have to be at the point of
signing up to get a copy!
- The Protocol Document
Every clinical trial is governed by a detailed plan called a protocol document.
The protocol document is absolutely not the informed consent document routinely
given to patients! Patients are rarely shown the protocol document and most
don't know such a thing even exists. But it's an absolute gold mine! The
disadvantage is that, of course, it's written in technical medicalease, so it's
going to take some mental mining to get the gold. It's worth the trouble!
The protocol document begins with a scholarly introduction which explains how
the treatment is believed to work and reviews the complete history of the
treatment, including all of the prior results, sometimes discussing results
which haven't yet been published or presented. You'll also find references to
all the published papers. This is the evidence you're looking for! (If there
are new results for related treatments since the protocol was written, it's
still possible that there's something more worth having.)
The protocol document also contains the complete treatment plan, including the
dose and schedule of administration (and in a phase I trial the plan for dose
escalation), and rules for when to stop treatment or reduce or skip doses. This
information can be surprisingly useful. In my own case the protocol compared
the doses in my trial to those used in other studies, and I was able to verify
that I was getting a high dose which was one of my goals. I also learned that
the investigators were particularly concerned about neurologic side effects and
would skip or reduce doses at the first sign. During treatment, I found I was
plied with optional sedative drugs, pain killers, sleeping pills, anti-nausea
medications. Based on what I'd read in the protocol document, I elected to go
light on the use of these drugs. I believe this contributed to my ability to
get all of the treatment.
Unfortunately, it's completely impractical to try to get the protocol document
on every trial you might qualify for. It's more appropriate to try to get it
for trials you already know you are seriously interested in. If your doctor
offers you a particular trial, and you're seriously interested after the
initial discussion, it would be very appropriate to ask for a copy of the
Doctors vary in their willingness to let patients see the protocol document. My
doctor, seeing my interest in the technical data, volunteered to give me a copy
without my even asking. In truth, I had no clue there was such a thing! From
what I hear from other patients, some doctors refuse even when explicitly
asked. I think its an outrage to expect people to stake their very lives on a
trial while refusing to disclose crucial and readily available information! If
corporate confidentiality is the issue in a company sponsored trial, I would
offer to execute an Non-Disclosure Agreement, and even contact the company
directly if I could not gain cooperation from the doctor. If the time or
expense of copying is an issue, you could ask for only the introduction and
references, offer to pay the expense of copying, or offer to copy it yourself.
- Evidence from the Trial So Far
Surprisingly often at least some evidence is available about the very trial you
are investigating even though it's still in progress! Often something about how
it's going is known before the end of the trial. Of course, by its nature,
evidence from ongoing trials is likely to be preliminary and uncertain.
- Informal Information From The Doctors
Especially in phase I and II trials, the doctors may well know whether any
patients have responded to the treatment so far, and whether the responses are
holding (In Phase III or adjuvant trials where the bottom line is the
comparison between the arms, an informal guess is entirely meaningless.) It is
likely that the doctor will be willing to share what he knows. Many trials are
multi- institutional and any one doctor may have treated only a small fraction
of the patients. You may be able to get more specific information if you
tactfully ask more specific questions in response to general answers, just
don't be surprised if they don't know all (or even most) of the answers. They
should be able to at least give some basic information about side effects.
Some Questions to Ask:
- Number Treated: How many patients have been treated so far?
- Responses: How many patients were evaluable for response? (It takes
a while before a patient has gotten enough treatment to be evaluated for
response, so they may have no information on response even though several
patients are in treatment.) How many patients responded to the treatment? How
many of those responses were partial and how many complete? Are any of the
responses holding or are patients relapsing? How long is the longest follow-up
- Side Effects: What have the usual side effects been? Have there been
any life threatening side effects? Have the side effects resolved when the
treatment was stopped? Or does there appear to be permanent damage?
- Informal Information From Other Patients
If you are part of a large, well informed, group of patients dealing with your
particular cancer, there is a chance that some of them may be participating in
the very trial you are investigating. This is information you can easily
understand with a personal touch They may also have heard some not generally
known information about the current results from their doctors.
The disadvantage is of this kind of information is that the information it's
reported by patients who may not have a clear idea what their results really
are, fragmentary, and often second hand. Trying to gauge efficacy with this
kind of information is really only possible to advanced poor prognosis cancer
where any hint of efficacy can be a reason for hope. Even if you aren't in this
situation hearing personal stories about participating in the trial can put
things in perspective. If you are fortunate enough to get a "hot tip" from a
patient group, be sure to take it as just a starting point for a much more
careful investigation including, of course, contacting the doctors doing the
If you join such a patient group you may also hear about very early promising
results from trials you weren't even considering. Most exciting is when several
patients in the group are actually part of some trial and are reporting good
results. This has actually happened on my kidney cancer e-mail list more than
once! Sometimes, we get a hint that something is promising long before the data
is published or even presented at a meeting.
The best place to find a large organized well informed group of patients with
your type of cancer is probably right where you are right now - online! As far
as I'm concerned, the best type of group is the e-mail discussion group. ACOR, the Association of Cancer On-Line
Resources, maintains the most extensive set of high quality cancer related
e-mail lists on the net. There is a list for almost every type of cancer.
- Interim Results Reported at Meetings
Sometimes interim results from ongoing trials are reported at professional
meetings, particularly if the results are promising or if there is a lot of
interest in a new drug or technology. Given most trials don't report interim
results at all, meetings are usually only once per year, and it takes time for
the information to be available on a web site, you have to get lucky for there
to be such a report on any particular trial available when you need it, but
it's worth checking by Searching the Web Sites of
Professional Societies. You might get lucky!
- Interim Analyses from Randomized Trials
The design of randomized trials often includes analyzing the data at pre-
defined points during the trial. If the data sufficiently favors one arm, no
further patients will be accrued. This both protects patients from being
treated with known less effective or more toxic treatment, and potentially
shortens the trial. In the most rigorous form of interim analysis, an
Independent Data Monitoring Committee analyzes the data at pre-determined times
and decides whether the trial should be stopped. Detailed information on how
each arm is faring is kept from the doctors who treat patients. It also turns
out that for subtle statistical reasons, the data has to favor one arm
particularly strongly before the trial is halted. So the mere fact that the
trial has passed an interim analysis tells you very little about whether one
arm is doing significantly better.
In some trials less formal interim analysis may be done and it's possible that
the doctors do have information. So it's still worth asking if there's been an
interim analysis and what the results were. If you get a bland answer that the
analysis didn't show a difference, you might tactfully press for any more
detail on how much of a difference was seen and how statistically significant
the difference was. You might also ask if anything's been presented at a
This CancerGuide Page By
Steve Dunn. © Steve Dunn
Page Created: 2002,
Last Updated: Jan 15, 2002