It is a perfect day for bananafish.

CatcherI remember one summer when I was 14 and I read every single word ever written by J. D. Salinger that I could get my hands on. An intravenous bolus infusion of JDS you might say, that went straight to my head without any sober literary criticism as intermediary to spoil the rush. Several years later I met my husband to be. I never told him this but I think I married him because I thought he was a bit like Seymour Glass. Raise high the roof beam, carpenters..  Like Ares comes the bridegroom, taller far than a tall man.

Today seemed to be a good day to remember the intense need for authenticity and altruism I felt back then. I am sure many of you went through similar periods in your lives. Some vague stirrings of the same feelings still remain but mostly silenced by the ravages of time, chromosomal damage and deletions to my altruism genes that no FISH test can hope to capture.

If you are not a fan of J. D. Salinger and don’t get some of these mantras true devotees know by heart, don’t worry. You may still enjoy reading the rest of this article. I will warn you guys upfront though.  Most of this article is my own perspective, editorial comments from yours truly.  Take it or leave it, as it seems right to you.

Our life blood draining away

Clinical trials are at the heart of all hope for patients like us inflicted with incurable diseases. Without well conducted clinical trials and the credible lessons and results learned from them, we would still have only chlorambucil as therapy option. Research done in glass dishes or mice does not (repeat, not) guarantee things will pan out exactly as expected when tested in human subjects. Clinical trials are expensive, time consuming and have become very frustrating for all concerned. Really large sums of money ride on the outcome of pivotal drug trials – and that complicates things enormously.

But clinical trials are still the life blood of all future developments. Without well conducted clinical trials there is no hope that CLL and other such incurable diseases would ever be cured. Without patients willing to volunteer for clinical trials the process grinds to a halt.

Our clinical trial process is truly busted

And that is putting it mildly. As the excerpt below from a recent article points out, percentage of patients who volunteer for clinical trials is dropping like a rock. You can read the full length article by clicking on the link.

November 1, 2008

Oncology News International. Vol. 17 No. 11

Clinical trials struggle to recruit, retain patients


An alarming 80% of US trials are delayed because of poor enrollment. Experts share what’s being done to close the gap between patients’ awareness of trials and their actual participation.

It’s no secret that enrollment into cancer care clinical trials has reached a level that could be described as anemic. Conventional wisdom puts adult enrollment at 3% to 5%, even though two-thirds of cancer patients say they are receptive to participating.

“Two surveys of cancer survivors conducted in 2000 and 2005 suggest that 4% is probably a real number,” said Robert L. Comis, MD, president and chair of the Coalition of Cancer Cooperative Groups (CCCG) and chair of the Eastern Cooperative Oncology Group (ECOG). A recent survey of 9762 patients by the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) found only a slightly higher rate, 5.5%.

Either way, the number is “distressingly low,” Dr. Comis said.

Why are patients shunning clinical trials?

There are lots of reasons why this is happening. Here are some contributing factors that I would like us to discuss:

  • There are too many me-too type clinical trials funded by well heeled drug companies looking for larger market share and bragging rights. Such trials siphon off the bulk of patients that are looking to participate in clinical trials. I am sure many of you have heard of scandals where drug companies do a series of very similar trials – then pick the ones which happened to give the best results to get FDA approvals and market share.
  • Major institutions such as the Mayo and M. D. Anderson with heavy flow of patient referrals have a built-in advantage, directing their patients to participate in the specific trials they happen to be sponsoring at that point in time. Smaller trials at less well known institutions suffer by contrast, even if they have good ideas and good science to their credit.
  • Not all good therapeutic ideas are necessarily good commercial ideas that will make some one or some company very rich. The EGCG (green tea extract) trial would have languished a lot longer for lack of support if CLL Topics (and our generous patient community!) had not stepped in to support it.
  • Science is getting awfully complex. Most patients have no chance of really understanding what is involved in participating in a clinical trial. How do you make informed decisions involving life or death, if you cannot get a good fix on the risks and rewards involved? And no one takes the time to explain things to you in language that can be understood by laypersons?
  • Most patients are seen by local health-care providers who have no incentive in recommending clinical trial participation. First, it takes a great deal of effort to stay fully informed about all the various trials out there, for all the different kinds of cancers treated by local oncologists. Second, why would a good businessman (and most doctors’ practices have to be businesses to survive these days) send away a paying customer to someone else? Where is the profit in that?
  • Some insurance companies will cover the cost of drugs and therapy that is not covered by the clinical trial itself. But who will pay for all the travel and living expenses incurred? Most trials require you travel to their site several times during the trial itself and for follow-up.

The brand that is on sale today ..

A couple of years ago I got to know a very wealthy and determined member newly diagnosed with rather aggressive CLL. He got disillusioned with his local oncologist pretty quickly, for the usual reasons. He wanted nothing but the best in treating his disease, and he told me he can afford the best. He asked me for the names of the top five CLL expert centers to visit. He wanted to get guidance on his specific case from the best minds in the business.

I gave him the names of the five best centers – most of you who have been round the block for a few years can guess them easily. I also gave him a sealed envelope with the therapy recommendations I expected he would get from each of the five centers he was going to visit: FCR, PCR, flavopiridol, “gene therapy” and Campath.

My friend went to each of the five centers in turn, asked each expert he met to do detailed testing and prognosticating, expense be damned, and come up with the best therapy option custom-designed to his particular needs. Each center obliged, at significant cost. My friend is wealthy and did not care about that. Heck, he wore nothing but custom made clothes and custom made shoes, lived in a custom designed home that he shared with an almost-custom sculpted wife (snicker), why should he not get custom made therapy for his cancer?

He came back from his voyage of discovery chagrined and confused, with five completely different recommendations from the five expert centers. He then opened my sealed envelope and I am pleased to say I was spot on in my guesses. I could have saved him all that fuss and expense. I got all five recommendations exactly right and matched each recommendation correctly to the expert center. Each center felt the particular clinical trial they were focused on at that particular time was the best suited therapy option for my friend.

(Pop quiz: can you match each of these therapy recommendations with the expert center most likely to have made the recommendation? If you can, give yourself a pat on the back, you are now a savvy consumer of health-care.)

How can this be?

How can there be such divergence in opinion between different expert centers? How can we trust guidance that is so influenced by local biases?

The answer is complex. First, researchers are human beings too, with their own built in human biases. How can one work for decades at developing a particular drug protocol without developing a certain amount of personal bias in its favor? Heck, each of us thinks our kids are the brightest, prettiest kids on the block!

Second, institutions spend a lot of money running their clinical trials and it is crucial to get a steady flow of volunteers lined up to participate. Institutional prestige and reputation (not to mention large scale endowments) ride on it.

Third, reputations and careers of the scientists involved are made by successful clinical trials that progress rapidly through the various stages and become commercial successes. Ditto for commercial profits of companies that own patent rights for the drugs involved.

Fourth, and this may come as a shock to some of you, some drug companies actually pay head-hunter fees (thousands of dollars per patient recruited) to local oncologists that bring them new recruits. Money buys a whole lot of influence – ever been to one of the ASH conferences?

Where in this dog’s breakfast mess of conflicting agendas does the individual patient’s welfare figure? How many experts are able to wear two or more hats? That of the brilliant scientist and admirable researcher on the one hand, and the caring physician looking for the best custom-fitted therapy option for the patient sitting in front of him – and do justice to both agendas? Where does multi-tasking end and conflict of interest begin? And how can you as the hapless patient tell the difference?

Thinking about it, any wonder there is so little credibility left in the present process and patients are running away in droves from clinical trial participation?

Informed consent that isn’t

If you have ever signed up for a clinical trial or even considered the possibility, chances are you were given a sheaf of papers to sign – giving your “informed consent” to participate in the trial.

Anyone out there who bothered to read the full text of these documents (mostly medical and legal disclaimers aimed to protect the researchers, drug companies supplying the experimental medications and the institutions where the trial is being conducted) and thinks they were therefore truly informed? I mean anyone without advanced degrees in the sciences, preferably a double degree in hematology and oncology?

Much of the language is mandated by law and in my humble opinion, by a desire not to get sued. There is usually a laundry list of potential adverse effects all the way from a mild headache to instant death: a long and all-inclusive list that is all too often accompanied by a wink-and-a-nod by the research nurse handing out the papers. You are a smart patient, you know how these things work – the implication goes – these are just paperwork hurdles that “they” force us to jump.

Every early stage clinical trial disclosure contains language to the effect that participation in such early stage trials is not (repeat, not) meant to be of therapeutic value to the participants, the intent of these early attempts is to establish the right dose and judge toxicity. How many of you are still convinced that participating in early stage trials may still have terrific therapy value for you because the science so sexy and the researcher has a terrific bedside manner? This is what I mean when I talk about the wink-and-a-nod approach to “selling” clinical trials. I have a great deal of admiration for all clinical trial volunteers. But I am old fashioned, I also believe in the individual’s rights to make decisions with his/her eyes wide open. Coerced altruism is another name for a sucker’s game.

Bewildered patients often take the path of least resistance, assuming all the advisories and cautions are just so much bureaucratic nonsense to be disregarded immediately. All of us are guilty of signing on the dotted line without reading the fine print at some point in our lives. Heck, I find the fine print that accompanied a recent credit card application could not be read even when I got me a magnifying glass – justifying the label of “fine” print indeed. Mandatory “Plain English” laws do not help much either. It just forces the researchers to dumb down the disclaimers. The fundamental problem is that the science involved is often just too complex to explain to a lay audience in a few pages of text, or over a 15 minute consultation, by harried healthcare providers.

I believe the law of the land requires banks give customers several days over which to consider the terms and conditions of their mortgage. Customers can take home the full set of documents, mull them over, ask their accountant brother-in-law for his take on it, do a bit of human dithering – and then make the decision that is right for them.

Compared to that, do you know most clinical trial protocols are classified as “confidential” and patients are discouraged (if not forbidden!) to discuss it with their own trusted advisors? In any other industry this approach would be called giving the mark the bum’s rush. Fortunately, a lot of patients trust my promise of confidentiality and do share their clinical trial protocols with me, and when requested to do so I am honored to give them my two cents.

It is unfortunate that the real risks are often overwhelmed by the long and often trivial list of low impact or low probability risks that are neither here nor there. I mean, as patients facing an incurable cancer, is it really pertinent to worry about the potential risk of grade I headaches that may or may not happen? That you may up-chuck a couple of times? I am far more interested in knowing about, say, Stevens-Johnson syndrome. What the heck is that? My next door neighbor is named Steven Johnson – he is not dangerous at all, in fact he is a real sweetheart and does my lawn for free. Any syndrome named after him cannot be all that dangerous, right? (Wrong!)

Looking at the problem of getting informed consent from the perspective of the researchers, I have to admit they have a valid beef with the whole concept. Science is developing at a dizzying speed. Concepts are getting ever more complex. Even trained MDs are having trouble keeping up. How can doctors explain such complex issues to layperson patients in a reasonable amount of time? Medical school does not train doctors in the art of teaching science to non-scientists. (Tooting my own horn just a little, my doctorate from the University of Michigan was focused on exactly that: teaching science to non-scientists)

You drive this bus. What say you?

Whether or not you are newly diagnosed and in W&W, about to start therapy or happily smoldering away, participating in well designed and well conducted clinical trials are an option worth considering.  Here are some of the roadblocks.

  • Does your doctor (local guy) bring one or more clinical trial options to your attention? Does he explain the pros and cons to your satisfaction?
  • Do you feel when you sign up for participating in a clinical trial you are doing so fully aware and informed about your risks and rewards? Did the researcher do a good job of explaining things prior to your recruitment?
  • Do you trust your doctor / researcher / expert to put your welfare ahead of his desire to recruit patients for a clinical trial that he wants to see succeed, for whatever reason?
  • Do you get a chance to mull things over, discuss with outside advisors, before you had to make a decision? Was there a sense of getting the bum’s rush?
  • Will you volunteer for a clinical trial even if you personally will not benefit from it, but you like the idea of doing something to help other patients? Possibly your kids or grandkids?

Some people are proposing more aggressive marketing targeted directly at patients in order to “sell” clinical trials. How does that concept grab you? Frankly, it scares the living bezeesus out of me.

January 1, 2009

Oncology News International. Vol. 18 No. 1

Clinical trials benefit from aggressive patient outreach


Good public relations are part of any successful business, and cancer trials are no exception. Drs. Charles Weaver and Robin Zon discuss their tactics for recruiting patients in this alarming article.

Living the ‘authentic life’

Not everyone gets a chance at redemption and salvation in their lives. If you are a patient who volunteers to participate in early stage clinical trials that may have no therapeutic benefit for you but might, just might, improve the lives of future generations of patients, in my eyes you have become a grown up and responsible version of a “Catcher in the Rye”.

If not you, then who?

If not now, when?

If not with your eyes wide open, why bother?