Thursday, March 31, 2016

Outrageous! Doctors Earn Luxury Goods by Answering Pharma Funded Surveys

(A quick note: Sorry about the extended time between blog posts, but I was dealing with some nagging respiratory yuckiness that left me with barely a voice, which makes writing blog posts using voice recognition software damn well near impossible. MS has made typing out of the question, thus the long hiatus. Well, now my voice is back, and so is the blog…)

Okay, here’s one for the “you can’t make this crap up” file.

A physician friend of mine – who shall remain nameless lest he/she incur the wrath of the Pharma beasties – forwarded me the following note they received via email, offering a generous rewards program in return for answering questionnaires designed to gather information that would help pharmaceutical companies maximize their ability to impact physicians' prescription writing inclinations, or, as the note less ominously puts it “to observe and improve the quality of the information you receive from the pharmaceutical industry”. The message came from a marketing/data mining company that uses sophisticated methodologies to maximize marketing, branding, and product launches in the health services industries. My physician friend tells me they receive several such emails every week.

Here’s the note, with any identifying or proprietary information redacted so that I don’t get sued for publishing it:


Dear Dr. XXXXX XXXXXXX

We would like to invite you to join our regular study on the medical information delivered by pharmaceutical companies. The objectives of this study are to observe and improve the quality of the contacts and information that you receive from the pharmaceutical industry through:

o individual interactions (in person and online)

o events (in person and online)

o direct mail (postal and email)

o clinical trials and product samples

As we work to help improve minor modifications to better align with your activity. These will allow life science researchers to measure your perception and satisfaction with the aim of adapting and improving the quality of information you continue to receive.

To thank you for your time and participation, we offer generous incentives which allow you to earn and accumulate points for each questionnaire you complete. The more questionnaires you fill-in, the more points you earn. We also offer loyalty program which rewards you 25% more points, if you participate for 12 consecutive months. At any time, you can use your points to redeem:

o   Flight tickets to destinations in the Caribbean, Europe, Central & South America, Asia, Australia and South Pacific, Africa and Middle East, Mexico, Canada and the US

o   International and domestic vacation packages including tours, sightseeing and cruises

o   Admission to theaters, concerts, sports events, amusement parks and many outdoor adventures

o   Merchandise including home appliances, furniture, home and garden products,  jewelry, toys, baby products, apparel, tools, office supplies, outdoor products

o   Health and Fitness products and equipment

o Electronics including TV, audio/video equipment, cameras and camcorders, computers, Apple iPads, iPhone, video games and consoles, GPS devices, printers/copiers

You can preview our incentive selections from our website at XXXXXXXXX.com using the trial login "XXX" and password "XXXXXXX"

To sign up, simply complete the form below with your preferred contact information. You can fax it back to me at XXX – XXX – XXXX or e-mail at XXXXXXXXX.com

Doctor name:                                                        First/last name:   
Specialty:  
Phone and  fax:
Mailing address:    
Email address:


If you have any question about the survey or the incentives, please call me at this toll-free number XXX – XXX – XXXX. I will be more than happy assist you.


PLEASE NOTE:  This e-mail and any attachments may be confidential or privileged and is solely for the intended addressee(s).  Do not share or use without XXX approval.  If received in error, please contact the sender and delete the email and any attachments.

 
Wouldn’t you like to earn international vacation packages and high-end luxury items just by answering surveys? Well, if you would, you’d better become a doctor. Because, you know, doctors need all of the financial assistance they can get since they are so underpaid in relation to those in other professions, like schoolteachers (who really make me want to retch, the hedonistic bastards).

I took the liberty of perusing the catalog of items available via the survey rewards program, and found that they include goodies ranging from free music downloads to high-end appliances and home furnishings to every kind of electronic gadget imaginable to European vacation packages. A single music download will cost a participating physician 278 points, front row tickets to a New York Rangers hockey game in Madison Square Garden (including food and nonalcoholic beverages) 337,489 points, and an unlocked 64 Gb Apple iPhone 6 plus 205,363 points. Oh, and a 15 night transatlantic cruise leaving from Rome and arriving in Miami, with stops in France and Spain along the way, will set some lucky questionnaire answering physician back 466,277 points (per person), which seems like a heckuva bargain given the cost of the hockey game.

Of course, it’s not the marketing company that is footing the bill for these “rewards”, but their pharmaceutical company clients. And why would pharmaceutical companies be willing to pay through the nose for information that would allow them to hone their messaging to doctors? Simply put, because the doctors know damn well where these rewards come from, and studies have documented that rewarding doctors with cash or goods has a quantifiable effect on their prescription writing practices. One such study (click here and here) found that “Even small handouts--such as free meals and payments worth $100 or less--tweaked branded scripts upward. Doctors who participated were two to three times more likely to prescribe brands than those who didn't. There was also a dose response: The bigger the value of payments and gifts, the more branded scripts… Doctors who received more than $5,000 in a year's time chalked up the highest percentages of branded scripts.” And make no mistake, pharmaceutical companies carefully track just how many prescriptions for their drugs doctors are writing, and routinely use such info to target those physicians who are “underperforming”.

It’s well known that pharmaceutical companies regularly pay the doctors who prescribe their products cash money, in the form of "consulting fees” and “honoraria”. More often than not, these consulting fees and honoraria are paid to doctors who simply talk to other doctors about a prescription drug, quite often over a free meal at a fine restaurant, or for giving a presentation on the drug at a symposium. Some doctors rack up tens of thousands of dollars per year in these fees, as has been made public via the Open Payments website, which was mandated by the US government in the Affordable Care Act.

While the Open Payments website itself is not all that user-friendly, the organization Pro Publica has built their own patient friendly portal to access the database, called “Dollars for Doctors” (click here). This website makes it extremely easy for patients to enter their doctors’ names and locations and come up with a list of all of the pharmaceutical company payments their doctors received from August 2013 to December 2014. Believe me, some of the numbers will shock you. One physician, a family medicine doctor in California, received nearly $44 million for “promotional speaking/other” during the 18 months in question. Yowza, for that money he must be quite the electrifying speaker, able to talk to the green off of an iguana. Using the site, I found that my first MS neurologist netted $72,580 during that time period, while my current neuro received a grand total of $17, which is one of the reasons he’s my current neuro.

It’s because this information is so accessible that pharmaceutical companies are finding new and more creative ways to funnel money and rewards to doctors, ways which bypass the laws and never see the light of day, such as handsomely rewarding doctors for answering questionnaires. Pharma has also increasingly taken to paying for physicians Continuing Medical Education (CME) courses, a practice that has seen a 25% jump since 2011 (the mandate that dictates public disclosure of physician payments went into effect in 2010).

All of this begs the question, how on earth is it tolerated, never mind legal, for pharmaceutical companies to pay the physicians who dispense their products? To my knowledge, this is the only industry in which such widespread and lucrative “consulting fees” and “honoraria” are considered everyday business. In most other lines of work such payments are called “bribes” and “kickbacks”. In the latter part of my career I worked for one of the major international music and entertainment conglomerates, and if we were caught paying a disc jockey to play one of our records (a practice known as “payola”) people would go to jail. Somehow, though, these practices are business as usual in the medical profession.

Pharmaceutical companies and the doctors who have their hands out frequently claim that these efforts ensure that physicians stay well-informed on the latest and greatest drug info, but are we really to believe that doctors would remain hopelessly ignorant if such palm greasing and wallet filling shenanigans were prohibited? What, would physicians suddenly forget how to read medical journals and the informational materials provided to them for free by the pharmaceutical companies? Has the Hippocratic oath been altered to state “First, do no harm. Second, information about pharmaceutical products not accompanied by copious amounts of dough shall be ignored”?

These issues are especially important to patients suffering from chronic diseases like Multiple Sclerosis who must rely on hideously expensive drugs, many of which carry with them a frightening list of potential side effects, to try to keep their disease at bay. We must trust that our physicians are choosing drugs and giving advice based on their keen medical insights and years of experience, and not because drug company monies have influenced their decision-making processes. The doctor-patient relationship for those suffering from chronic and potentially debilitating illnesses is a long-term affair, not a one night fling. As with all such relationships, trust is the beating heart of these partnerships, as life altering decisions hang in the balance. The fact that even the hint of financial self-interest on the part of the doctor might play a role in this complicated equation is, quite frankly, obscene.

I’ll now get off of my electronic soapbox, but I would encourage each and every one of you residing here in The States to quickly look up their doctors on the Dollars for Doctors website (click here), to see just how much financial benefit your physician has reaped through these dubious practices. This is not to say that every physician receiving large amounts of money from the pharmaceutical companies is corrupt, or has fallen under the spell of Big Pharma. But knowledge is power, and if your doctor has taken what appears to be more than their fair share, I’d say a frank conversation is warranted. No need to be confrontational, but certainly a cogent explanation would be welcome. Remember, for those of us suffering from long-term illnesses, the doctor-patient relationship must be a partnership, not a dictatorship. Ultimately, keeping yourself well-informed on all facets of the management of your disease may in fact be the very best medicine…

Hey, just for kicks, why don't those of you who do look up your doctors on the Dollars for Doctors website tell us how much pharmaceutical money your doctor received using the comments section of this post. Might allow us to contrast and compare… And vent and rant and rave…

Wednesday, March 2, 2016

Ocrelizumab PPMS Trial Data Released, Offers Reasons for Hope and Concern

Last month, at the annual ACTRIMS (American Committee for Treatment and Research in Multiple Sclerosis) conference, the full trial results for the Ocrelizumab PPMS drug trial were finally revealed. These results had been much anticipated by the MS community, as there are currently no proven effective treatments for Primary Progressive Multiple Sclerosis, and many previous PPMS drug trials have ended in failure.

Coincidentally, a few days before the conference, Ocrelizumab received “fast-track status” by the FDA (click here). The “Fast-Track” designation is given to drugs which promise to fill a prior unmet need, and generally shortens the approval process from 10 to 6 months. Since PPMS has no approved treatments, Ocrelizumab fits the requirements for the designation. Though fast-track designation means that Ocrelizumab will have an expedited approval process, it does not guarantee that the drug will ultimately be approved.

The anticipation over Ocrelizumab, which was developed by Roche Pharmaceuticals subsidiary Genentech, stems from the fact that trial results appear to demonstrate the drug to be effective in slowing down progression of disability in PPMS patients. In results presented at ACTRIMS, Ocrelizumab showed itself to be very potent in treating RRMS (click here), and in PPMS the drug slowed down disability progression by 24% (click here), making it the first major pharmaceutical product to demonstrate effectiveness in treating Primary Progressive Multiple Sclerosis in a scientifically rigorous placebo-controlled trial.

The data set presented at ACTRIMS confirmed info originally released last year, but the numbers revealed at the recent conference provided more details on the patient population included in the study (click here). Specifically, results were provided for two different subsets of patients – those with enhancing lesions (which signify acute immune activity within the central nervous system) and those without enhancing lesions. Only about 15% of patients with PPMS display enhancing lesions on their MRIs, and it was widely assumed that Ocrelizumab would likely only be effective in treating those patients. The results provided by Genentech at ACTRIMS , however, demonstrated that the drug appears to be just as effective in patients whose MRIs did not show any signs of enhancing lesions.

Great news, right? Well, if the numbers hold up it is great news, but there are certain aspects of the Ocrelizumab PPMS trials that raise some red flags. Ocrelizumab is a close cousin of the decades old drug Rituxan, which is also manufactured by Genentech. Both drugs work in almost the exact same fashion, by targeting and destroying immune system B cells, effectively ridding the body of the cells for periods of at least six or seven months. Ocrelizumab, like Rituxan, is administered approximately every six months, in two intravenous doses given one or two weeks apart.

Rituxan was originally intended for use against blood cancers, but was later found to be effective in treating a variety of autoimmune diseases, including Lupus, Rheumatoid Arthritis, and Relapsing Remitting Multiple Sclerosis. The human immune system consists of a wide variety of cells, but is primarily made up of B cells and T cells. Therefore, Ocrelizumab and Rituxan both eliminate a major component of the very complex immune system, which, it’s assumed, is why they are effective in treating so-called autoimmune diseases. Though Rituxan was never officially approved for use in MS, many MS neurologists prescribe the drug “off label” for their RRMS patients, in whom it has proven to be very effective in reducing relapses and the occurrence of MS lesions.

Back in 2008, trials of Rituxan on PPMS patients were deemed a failure, much to the intense disappointment of many patients, myself included. Subsequent analysis of the data generated by that failed trial, however, revealed that a subset of patients did seem to have a somewhat positive response to Rituxan – namely younger patients who displayed enhancing lesions, had been more recently diagnosed, and were less disabled than other trial participants (click here). Instead of pursuing more targeted trials with Rituxan, though, the drug’s manufacturer, Genentech, decided to develop a newer version of the compound, and thus Ocrelizumab was born.

Why invent a new version of an older, proven drug that uses the exact same mechanism of action as that older drug? Well, Genentech says it was done to develop a safer, more effective product, but a cynical person might point out that Rituxan had already proven itself to be relatively safe and quite effective but was due to come off patent in 2015, meaning that its window for generating tremendous profits was rapidly closing. By the time new trials were completed, Rituxan would no longer have patent protection. A new version of the drug, on the other hand, could be a golden egg laying goose. But, of course, only a very cynical person would point that out, not someone is bright eyed and bushy tailed as me.

Anyway, back to the current Ocrelizumab PPMS trials. Based on the lessons learned from the failed Rituxan trials, it looks like Genentech populated the Ocrelizumab PPMS trials with patients who were selected specifically because they were more likely to respond to treatment (click here). Whereas only about 15% of PPMS patients display enhancing lesions on their MRIs, the Ocrelizumab trial included about 27% of such patients. When compared to the trial’s placebo group, the patients that received the actual drug had twice as many enhancing lesions, meaning their disease was much more immunologically active. In addition, compared to other PPMS trials (all failed), patients in the Ocrelizumab trial were generally more recently diagnosed, and were much less likely to have been on any prior disease modifying medications (in the parlance of the medical research community, most of the patients were “treatment na├»ve”).

Still, when the numbers were broken down at ACTRIMS, they showed that the drug decreased the rate of disability progression by about 24% in both patients with enhancing lesions and without enhancing lesions. However, each subset of patients was too small to make these results statistically significant, meaning that the trial was, in the parlance of the medical research community, “underpowered”. Knowing that this was sure to be a very important issue, why would Genentech go ahead with a trial that was underpowered in this regard? Wouldn’t logic dictate that they design the trial to settle this vital issue in a statistically definitive manner? Seems kind of strange, no?

What may ultimately turn out to be the most troubling aspect of the Ocrelizumab PPMS trial, however, is that 11 cancers were detected in patients taking Ocrelizumab, versus only two in the placebo group. Eight of the cancers in the Ocrelizumab patients were breast cancers, versus zero in the placebo group. This is especially concerning because back in 2010, when Ocrelizumab was first developed, trials were started not only in MS but also on lupus and rheumatoid arthritis patients. Both the lupus and rheumatoid arthritis trials were halted because of patient deaths (due mostly to opportunistic infections), but the MS trials were allowed to continue because it was thought that MS patients would have a higher tolerance for risk (click here). Interestingly, in the Ocrelizumab RRMS trials, which actually included more patients than the PPMS trials, “only” four cancers were detected in the drug group, versus two in the placebo group.

Incidentally, in its over two decades of service, Rituxan has not been associated with the development of cancers or an alarming number of opportunistic infections, although rare instances of PML (the brain infection that is so concerning in patients taking Tysabri) have been seen in patients taking the drug.

If anything derails an FDA approval for Ocrelizumab in treating PPMS it may very well turn out to be the cancer issue. Even though the positive effect on PPMS generated by Ocrelizumab isn’t overwhelming (a 24% decrease in progression rates is nothing to sneeze at, but then again it’s hardly the dramatic effect PPMS patients are desperately seeking), on its own it would seem encouraging enough to garner an approval. However, given some of the questions regarding trial design and safety issues, it will be very interesting to see what the FDA decides. Another one time promising MS drug, Cladribine, was rejected by the FDA primarily because of cancers detected during drug trials (click here).

For some expert opinions on Ocrelizumab, here are two videos. The first is a video of Ottawa MS neurologist Dr. Mark Freedman discussing progressive MS in general, and then commenting specifically on the Ocrelizumab PPMS trial results. For those of you with short attention spans, he starts talking about Ocrelizumab at the 3:50 mark of the video. Dr. Freedman has some very interesting comments regarding the drug and its effectiveness, and B cell therapy in general. The video is well worth watching.





Here’s another MS neurologist, Dr. Clyde Markowitz, Director of the MS Center at the University of Pennsylvania, who seems much more enthusiastic about Ocrelizumab and its prospects for treating PPMS:





Being the always curious person that I am, and also hyperaware that drug companies often funnel money to doctors who prescribe their products, I did some quick checking and found that Dr. Markowitz received $64,461 from various pharmaceutical companies between August 2013 to December 2014, mostly for “consulting” and “honoraria” fees (click here). At least $6000 of this rather large sum came from Genentech, which, it turns out, was the number one drug company in handing out payments to doctors during that period (click here). And this was before the Ocrelizumab trials were completed.

One can only imagine that Genentech is now going all out to, um, “influence” key doctors in its efforts to get the drug approved, much like politicians target key precincts and states in their quest to get elected. I’ve done plenty of ranting on the subject of drug companies making direct payments to the doctors who prescribe their products in previous blog posts, so I’ll refrain from launching into yet another insane tirade here, but suffice it to say I’ve yet to find any logical argument as to why this practice is tolerated, much less legal.

In all fairness, since Dr. Freedman practices in Canada, I was not able to find any info on payments he might’ve taken from drug companies. The truth is that very few MS neurologists are not on the pharmaceutical company dole. I’d encourage you to enter your doctor’s name in the “Dollars for Docs” database (click here), and see if your neuro has his hand in the cookie jar. Again, this doesn’t mean that the doctors named in the database allow pharmaceutical company money to affect their decision making process, but then again, the pharmaceutical companies wouldn’t be doling out millions and millions of dollars if they weren’t getting an appreciable return on investment.

Okay, sorry, I got a little sidetracked there. I certainly hope that all of my concerns about Ocrelizumab turn out to be completely unfounded, as having even a modestly effective treatment readily available for PPMS would be a major step forward in fighting the disease. However, it seems clear (to me, at least) that going after the immune system isn’t going to be the magic bullet that solves the Progressive Multiple Sclerosis problem, or the broader overall Multiple Sclerosis riddle.. Researchers urgently need to step outside the box and start coming at the issue from new angles if any truly dramatic progress is ever going to be made. In the meantime, here’s to hoping that Ocrelizumab proves itself to be a safe and reliable option for Primary Progressive patients, whose desperation for proven treatment options is beyond words.