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 particular trial.
Which Trials to ResearchBefore 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 qualify for!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 research.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 LiteratureYou 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 TrialsThe 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 DocumentBefore 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 DocumentEvery 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 protocol.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 FarSurprisingly 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 DoctorsEspecially 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 so far?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 PatientsIf 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 trial.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 MeetingsSometimes 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 TrialsThe 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 meeting.