That’s why they call them “trials”

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Given the times we seem to be in, maybe you’re thinking you’re about to read a blog about the trials and tribulations of Donald Trump, who can’t seem to tear himself away from the big bucks of an NBC contract to run for President, or the upcoming trial of Dominique Strauss-Kahn, managing director of the International Monetary Fund, on rape charges, or

He was as bad a governor as he was a husband

the struggles of Maria Shriver, who turns out to have been married to another male politician who can’t seem to keep his pants zipped.

While those topics are undoubtedly more fun to explore, they are not my subject today. I want to address the serious topic of drug clinical trials, a topic that most people who aren’t doctors – and, tragically, some who are – don’t understand.

What is a drug clinical trial?

Clinical trials are used to advance scientific research into the treatment of illnesses.

A clinical trial is a medical research process used to determine if a drug is (1) safe for humans to take and (2) effective to treat the medical condition that it is intended to address. The drug under investigation – called the treatment — is compared to what is called a “control,” which is either a placebo (a pill or infusion that looks like the drug under investigation, but that has no biological properties) or an existing treatment for the condition, so that researchers can determine whether the drug under investigation is more effective that the alternative to which it’s being compared. The treatment group of patients and the control group of patients have to be balanced in number so that the results of the trial are meaningful.

Drug trials are necessary because, without them, there is no way of knowing whether the treatment drug that is the subject of the trial will work for the patients in the trial.

There are a couple of other features of well-designed trials that are important to try to insure that the outcomes of the trial reflect how the drug being tested works, rather than any sort of bias on the part of those administering the trial. These features are randomization and blindness.

Randomization is the process by which patients in the trial are assigned to receive either the drug under investigation or the control. By assigning to patients at random, researchers avoid any bias that might creep into trial results by choosing, for example, the apparently healthier patients to receive the drug, or the less-healthy patients to receive the control.

Blindness refers to who knows what about which patients are in which group – the treatment group or the control group. Ideally, drug trials are “double blind,” meaning that neither the researchers nor the patients know which group the patient is in. Double-blind trials keep researchers from making judgments about how patients are doing based on what they are known to be taking. They may also keep patients from deciding to drop out of trials because they didn’t get into the treatment group. (Open-label trials – where both the patients and the researchers know what drug is—have become much more common in breast cancer than double blind trials.)

A drug trial is considered a success if the patients getting the treatment drug do better than patients in the control group by a statistically significant percentage. A successful trial tells nothing about whether the treatment drug actually worked in an individual patient. After all, it’s possible that the patient would have improved without the drug in question. Miracles do sometimes happen in medicine, and not necessarily because doctors make them happen.

Clinical Trials in the Abstract

I know a lot about clinical trials from my work as a breast cancer activist. From that work, I have come to believe that trials should demonstrate that the drug being tested can do at least one of three things before it is marketed to the public:

-       Improve survival

-       Improve quality of life

-       Cost less than existing, equally effective treatments

 

These ideas about the goals and structures of clinical trials are fine in the abstract. It’s harder when they have very personal implications, either for you or for someone you love. While no promises are ever made to patients entering clinical trials, it’s hard for the patients or the people who love them to not believe at some level that the drug under investigation will improve their lives. People often enter trials believing this, no matter what they are told about the purpose of the trial.

The personal side

That my friends share this belief was evident when I told them that I was being screened to see if I’m eligible to be in a clinical trial. Many have hoped for me that, if I was eligible for the trial, I would get the drug being investigated, not the control, which in this case is a placebo. That hope seems to convey the belief that the drug will work. Whether it will or not is, in fact, what the trial is intended to test.

I know that participating in a clinical trial means taking a chance that I won’t get the drug under investigation, as well as the chance that that drug won’t work anyway. I know that it’s impossible to know from a clinical trial whether the drug under investigation will help me, even if it shows benefit for a significant percentage of people in the trial.

At the same time, I know there is only one approved treatment for ALS, the disease I have. At best, that treatment delays progression. Better treatments are needed: ones that will extend patients lives or improve the quality of the lives they live with this devastating illness. I know that only through clinical trials can better drugs be found, and I hope that this trial – and other trials –will advance the knowledge of what does and doesn’t work to treat ALS.

And I’ll also keep in mind, as I enter the trial that placebos also work sometimes.

© Barbara A. Brenner 2011

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17 Responses to That’s why they call them “trials”

  1. Zelma says:

    I wish you well. I did one for Multiple Sclerosis and I feel that my ‘contribution’ has helped others to prolong their lives in a more meaningful way. Although western medicine is very intrusive and awful I feel really good that I did the study. Barbara take care and I will thing of you and remember always what an incrediably brave and fierce woman you are!

  2. abby abinanti says:

    Screw science…if there is a chance something will work give it out….if i doesn’t work then “oh damn”….if they think that equates with fair – double blind – it reminds me of Ghandi’s statement if you take an eye for an eye everyone ends up blind….

  3. Sandra Steingraber says:

    The ongoing tribulations of Maria Shriver and Mssr. IMF are as old as the hills. Your upcoming trial, by contrast, is terra incognita.

    I am so grateful that you are, as much as possible, taking us all with you on the journey. I’m following close behind and paying attention.

    This is the best description of a clinical trial that I have ever read. Thank you for that, too. [And for your tuna salad recipe! Capers! Really?!]

    My mom remembers that, at age 46, she was one of the first metastatic breast cancer patients in Peoria to receive cytoxin. (This would have been in the mid-1970s.) Her treatment wasn’t part of a clinical trial, but she said that it felt like one. Her doctor accompanied the scrip with a breezy, “here’s something new; we might as well try it.” Then, on her way out the door, he encouraged her to go home and “make your husband’s life as a pleasant as possible in the months remaining to you.”

    Probably that’s not in the clinical trial script. Barb, you know the punch line to my mom’s story: she’s turning 81 in September. The prescribing doctor died. Of cancer.

    Mom also said something else about undergoing chemotherapy at a time when it was a complete novelty: “You know, this would be completely fascinating…if it were happening to someone else.”

    sending you all best wishes from the F terminal of the Philadelphia airport

    Sandra

  4. Wendell Ricketts says:

    I’m totally in favor of double-blind trials for, say, a new cure for jock itch, but not for disabling and/or life-threatening diseases. Though having come through years of ACT-UP certainly hipped me to the issues, anyone ought to be able to realize how cruel such trials are. I’m glad you got in, sweetie, but I still say the system sucks.

  5. mary Whitehead says:

    Again, Barbara, continued “kudos” for your clarity and advocacy!!! I believe it is also OK for a patient to decide NOT to enroll in a clinical trial, if they have studied the parameters of the trial, and have unresolved questions. One issue which I believe has yet to be resolved is, if a med is in clinical trial(s) and could do a patient harm (perhaps unknown at the outset) there often is no medical coverage for follow-up for the patient during the trial’s term. Some other things bother me. This is just an alert to remind patients that they have a say in the choice of entering a trial. They shouldn’t be impressed by any medical staff suggesting that the effects of any trial will result in improvements of the disease in question.

    By the way, how do I learn about your tuna salad recipe???

    Love to you, Mary

  6. Ellen Leopold says:

    Such a clear description of a complicated business. Thank you.

    I hope you will tell us, if you are eligible and choose to enter this trial, something about its economics. I would like to know who funds it (private or public sources? a mixture of both?) Is the manufacturer of the drug under investigation a sponsor? And what costs, if any, fall on the participants? I would also like to know, if and when you enroll, whether the trial administrators provide you with this information up front, as a necessary part of the process seeking your informed consent.

    • bbzinger says:

      My pleasure, Ellen.

      I mention in the blog post you just read, and on our Caring Bridge site, that I am eligible, and I will enter the trial. Here’s what I know in answer to your questions:
      Major funder is the drug manufacturer, with some participation, I believe, by the Forbes Norris Center. No costs fall on the patients. I was provided with this information as part of the informed consent process. I have the form on email if you want to see it.

  7. Kim Klausner says:

    Barbara, you’ve explained this very succintly. Good luck.

    Study design is important but hard for lay people to evaluate. For example, under what criteria are people accepted/rejected as subjects (I’ve heard of trials for drugs that will be used mainly with older people recruiting mainly younger people)? How large is the sample (bigger is better) and for how long is the study conducted (a short study is more likely to achieve better results)? In the case of safety trials, at what point are non-endpoint safety analyses done and under what criteria will the study be ended? If the study is a joint project between academic researchers and a drug company, who has control over the data and publication rights? Is the Institutional Review Board (IRB) that oversees the study part of an academic institution or a for-profit venture?

    I think it’s great that you’re doing this, don’t get me wrong, it’s just that I’ve done too much reading about drug companies that put profits before safety/efficacy. An interesting article on this subject: http://www.bmj.com/content/334/7585/120.full?ijkey=921918ca4a99688ba972668f3875ec340d0e2d20&keytype2=tf_ipsecsha.

    –Kim

    • bbzinger says:

      Kim,

      As you know, I know about all of these concerns. The purpose of my blog was basically to give a clinical trials 101 for people who don’t know all that you and I do.

      Here’s what I know about the questions you ask:
      – Criteria for acceptance/rejection have to do with disease state (not too advance, in general) and not being on potentially conflicting drugs
      – Sample size is 800, which is pretty large, given the rarity of ALS
      – Study length is 18 months, which given the life expectancy for ALS, is not “short”
      – I don’t know about the timing of safety analyses of the data, or safety criteria for ending the trial. I do know tha that, in the phase II trial, all patients were informed of all adverse side effects as they occurred
      – control of the data seems to be in the hands of the manufacturer
      – the IRB that is overseeing the study here (it’s a multi-centered trial) is CPMC, a non-profit hospital.

  8. Uma says:

    This whole conversation is really very interesting. I’m grateful to read all the Q&A that followed your very well communicated Blog, Barbara.
    I know you decided to apply and become a part of the trial, and that you got in. Thus, whether placebo or trial drug, for that reason I’m glad you’ll be a part of it.
    I’m very grateful to be a fly on the wall of this conversation, and of all those that have preceded and will follow.
    Deep love,
    Uma

  9. Alice Philipson says:

    Good luck. As you know, and part of what we for in HIV trials , was that if a drug showed great promise at one of the 2 things you mention, the trial was halted and everyone got the drug. Many current trials fOllow that path now.

    Its a good thing to do. Bad enough to die, but if some good can be done on the way out; so much the better. My docs are still trying to figure out why I am alive. I spit into dishes so they can assey my genes…… I was, am & will always be Involved. You too.
    Alice

  10. helen jacobs says:

    this is not a comment, just a question from non tech-y me. if i want to send this blog on to others, what exactly do I have to do to make it happen. I have a friend who recently went through a year of breast cancer treatments and I think she’d be interested in reading your work.

    • bbzinger says:

      Hi, Helen,

      I sent you an email in response to this, but since other might have the same question, I thought I should also answer it here.

      The easiest way to tell people about this blog is either to forward the message you received notifying you of the most recent post, or to write a message to your friend with the web address here: http://www.barbarabrenner.net

      Thanks for spreading the word.

  11. Lorie Nachlis says:

    The theoretical part of double blind clinical trials makes sense to me. What troubles me is the huge profit motivation of the companies conducting the trials. The willingness to participate in a trial that may not benefit you but may benefit others can be commended, but we have seen that the benefit sometimes flows in unequal ways to a select group of individuals. This select group includes financial investors as well as a select group able to afford a particular drug. I think that the altruistic approach to resolving scientific uncertainty leaves me with a very unsettled feeling.

    This is a great blog.

  12. Ellen says:

    Thanks for the very clear way you’ve explained clinical trials. Whatever the downsides of a clinical trial are, because you’ve chosen to be part of this one, I congratulate you on being accepted into it. And for the same reason, I hope that you are part of the group being given the drug. And that the drug turns out to be effective, with no negative side effects.

  13. Walter G Bradley DM, FRCP says:

    Dear Barbara,
    A good friend passed to me you blog URL. I am very sad to hear that you have ALS. I have been looking after patients with the disease for more than 40 years and there is some hope…. it is not always fatal and there are many ways to fight it. I have written a couple of books that might help you and other suffers. One is “Treating the Brain” and it has a chapter on ALS. The other is the recently published book on the extraordinary insights and adventures of a patient of mine with ALS, called “Gib’s Odyssey”. Let me know if I can help in any way. I believe that you are in San Francisco, so you must know Bob Miller MD, a major figure in the ALS Neurology clinical and research community.
    Sincerely,
    Walter G. Bradley DM, FRCP
    Professor and Chairman Emeritus
    Department of Neurology
    Miller School of Medicine
    University of Miami
    Phone: 305-215-2144
    Fax: 305-964-5336
    Latest books:
    “Gib’s Odyssey”, Lyons Press, 2011. http://www.miamiherald.com/2011/05/03/2197319/final-voyage.html
    “Treating the Brain”, Dana Press, 2009. http://bradleyonthebrain.com, http://www.dana.org/news/danapressbooks/detail.aspx?id=21672

    ***The information contained in this transmission may contain privileged and confidential information, including patient information protected by federal and state privacy laws. It is intended only for the use of the person(s) named above. If you are not the intended recipient, you are hereby notified that any review, dissemination, distribution or duplication of this communication is strictly prohibited. If you are not the intended recipient, please contact the sender by reply email and destroy all copies of the original message. ***

  14. Helloman,
    This was an excellent page for such a difficult subject to talk about.

    I look forward to seeing more great posts like these.

    Thanks

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