Category: Clinical Trials

The Ethics of “Placebo-Controlled” Studies

Funny thing. When we hear the term “placebo-controlled study,” the methodological purists amongst us generally think that is a good thing. After all, without a placebo control arm, how would we know whether benefits apparently produced by a therapy were, in fact, actually placebo effects. But check this out. What you will see is a situation in which the circumstances of “placebo control” raise significant ethical questions. Why? Several reasons. Most tellingly, because the study participants were disproportionately “disadvantaged” inner city children of color.  AND. Because the placebo control involved withholding a standard treatment for patients with Vitamin D deficiency. AND. Because the study lasted almost a whole year, with standard therapy being withheld for this entire time for the control group. 

Bottom Line. Think about this one for a couple of minutes. The real kicker here is that this research could have been done without the placebo control arm. The reason it wasn’t?  It would have taken longer and been more expensive. 

The right question, as posed at the end of this piece, deals with how the heck institutional review boards at several major institutions signed off on this research. Exactly the kind of unethical research such boards are intended to prevent. 

How indeed!!!

Why Would Patients Care About “Statistical Significance???”

Check this out.  What you will see is yet another article that elicits a “DUH!” when you read it. A simple premise here. The clinical trials that the FDA requires for drug approval focus on “statistical significance.” Translated, drug companies have to demonstrate that their product is better than placebo. Yeah, but…From the patient’s perspective the real question on the table sounds more like “Is this drug good enough to help me with the condition for which I am taking it without causing unacceptable side effects?” That’s different.

Bottom Line. Again, the key takeaway from this article is a simple one.  If you want your new drug introduction to succeed, your research had best indicate that it is good enough to please patients, not just the FDA. Which in turn requires getting a good understanding of what patients’ expectations are for a drug in your treatment area.

Why “Bother” To Offer That Patient A Clinical Trial???

Several years ago, I made a presentation at what at the time was still PMRG (now Intellus) with a gentleman named Ross Weaver. (clinicalscore.com) Ross’s expertise is in the area of helping pharmaceutical companies “accrue” enough patients to complete their clinical trials. That’s often quite a challenge, and delays in trial completion are hugely expensive! In that presentation, Ross and I talked about how the principles of marketing can be employed in getting patients to sign up for clinical trials. I thought of that presentation when I read this interesting article. As with so many cases in healthcare marketing, this piece makes it clear that there are two customers here, and a complex marketing case to boot. First, we need to sell the doctor on enrolling in the clinical trial.  Then we need to sell the doctor on actually enrolling patients. Then we  need to help the doctor sell trial enrollment to their patients. Oh, I forgot. Last but not least, and often most challenging, is selling enrolled patients on continuing in the clinical trial to the end of their protocol. Read the referenced article closely. What pops out at me, as is so often the case these days, is the way the principles of Behavioral Economics can be employed here. Note the author’s comment that in some countries, the only way for the cost of a patients’ care to be completely covered is if they participate in a clinical trial. Behavioral Economists call this making trial participation the “default condition.” That makes me wonder, in turn, as to what other BE principles can be brought to the party here. Bottom Line. Maybe it is time for us marketing and marketing research types to visit with our companies’ clinical trials people and see if some of the new principles we are learning about in marketing, like those brought to us through Behavioral Economics, can be brought to their all-important work! Do you have any ideas, suggestions, or comments after reading this post? If so, stop by and leave a comment on the blog!

Noninferior???

NEJM Check out this snappy little summary of a clinical trial. Interesting at a couple of levels. First, we all know that there are a LOT of patients with chronic back pain. Managing their pain cost effectively is therefore of significant importance. The findings that yoga, which can be practiced in classes or even on your own, is as effective as the more expensive individual physical therapy is therefore of consequence. Right on! BUT. The thing that really caught my attention here was the word “noninferior.” And the concept of a “noninferiority trial.” From graduate school statistics classes until today, I have been trained to look for “statistically significant differences.” Something IS different/better than something else. The active drug is better than placebo. Etc. Here, the researchers apparently set out to demonstrate the absence of such superiority. Bottom Line. Let’s think about this one for a moment. Under what circumstances would a noninferiority trial be appropriate? My first response would be that it would be in situations like this, where one sets out to demonstrate that the cheaper alternative is just as good.    Are there other times when noninferiority is what we should be looking to demonstrate? Think about it!

Clinical Trials On Dental Flossing???

dental This little piece poses an interesting question. That is, how much should we value “randomized” clinical trials vs. other evidence vs. professional expertise and opinion. Here’s the deal. Forever, in the minds of regulatory bodies, professional journals, etc., randomized clinical trials were the sine qua non. BUT. Think about the example cited in the title above. How would you ethically set up a non-flossing control group in the face of expert opinion and common sense that clearly indicate that getting huge hunks of food out from between your teeth is a good thing? Bottom Line. Like so many “gold standards,” maybe RCT (randomized clinical trials) need to be rethought as the determinants of regulatory approvals, clinical guidelines, etc. Maybe, just maybe, we need to trust the experts. Maybe that is why we call them experts!

I’m Confused, And That’s Not Good!!!

Surgical clinical trials   Check out this NYT article. If I am reading it right, it seems to report data from a fairly large-scale study that found that spinal fusion surgery is ineffective, or at least no more effective than non-surgical interventions. BUT. Here’s my problem. For six months starting last Fall, my wife Casey suffered from lower back pain agony. And yes, she went for cortisone shots administered by a spine surgeon, and yes she went to physical therapy. The pain continued. Scroll forward. Almost 5 months ago, she had L4 and L5 fused by a spine surgeon on Hilton Head Island who specializes in this procedure. Today, I am EXTREMELY pleased to report that she is, quite literally, better than new. Golf is back, tennis is back, running is back, dancing is back. Surgery ineffective? Not hardly! Interesting. The same physician who eventually performed her surgery had said in our initial visits that there was an 80% chance that Casey would not need surgery. SO. I’m thinking that what that means is that if the majority of patients had surgery, it indeed would not be any more effective than were shots and PT. BUT. For the 20% of patients who, like Casey, had a preoperative MRI clearly demonstrating the constriction and scoliosis of her spine, the operation is a Godsend. And by the way, her insurance carrier (Blue Cross) paid every penny of the costs of the procedure. AND. This physician has an entire wing at our hospital reserved for his patients, and the surgeon’s name is known and praised across Hilton Head Island. Bottom Line. We have talked in recent blogs about the dangers of mindlessly looking at averages to evaluate the efficacy of therapies. Here is yet another case where individual differences among patients matter. A lot!!!

If You Think It Works…

Scientific American A recent study has found that the placebo effect for analgesics has gotten stronger in recent years. BUT, this finding has only been seen in America. Picture the impact of this on clinical trials. If you are a company trying to get a new analgesic product approved, you are having a harder and harder time beating out sugar pills. Bottom Line. Why? It has been hypothesized that Americans, who are the only patients in the world subjected to an ongoing barrage of DTC commercials for analgesics, have become brainwashed to believe that if they take a pill, any pill, that is purported to relieve pain, it will work. Except for the impact of this belief on clinical trials, this might not be such a bad thing! Think about it!

Debugging Clinical Trials

Health Hub Over the last year, I have been spending increasing amounts of my time consulting with Ross Weaver and Alec Pettifer on their work in the clinical trials arena. Fascinating stuff.  Helping pharmaceutical companies to make sure that their clinical trials don’t get “stuck” in the field. Finding stumbling blocks in the “Subject Journey.” Identifying trouble areas in subject recruitment/enrollment/retention, and figuring out ways to get patients over them. This is an important area of endeavor. It is estimated that 70% of clinical trials get “stuck,” and that the average cost of delay is $1 Million per day. As usual, pattern recognition is emerging from our body of work, but as always, we will take all of the insights we can get. Here, for example, is a seminal article from the Cleveland Clinic. Across the board, CC seems to have a better understanding of patients than any other organization I have encountered. Not a coincidence, I think, since they are also the most patient focused organization I have encountered.  Bottom Line. The article does a great job in identifying 10 common myths that block patient participation in oncology clinical trials. It is worthwhile reading in and of itself. But here is a bigger idea. Can you verbalize the 10 biggest myths that prevent patients from doing things you want them to do? the things that can get in the way of your creating a win-win for the patients and for your product? Take a clean sheet of paper and give this task a whack. If you need to do some marketing research to fill in the blanks, all the better!