Primary Care Corner with Geoffrey Modest MD: Drug Company Shenanigans, the Blogs Continue

By Dr. Geoffrey Modest

As an addition to the long list of prior blogs on drug company malfeasance (see link at end), there were a couple of relevant articles recently (since I have not railed against drug companies for a while)

1. The Office of the Inspector General of US Dept of Health and Human Services released a 13-page report on dramatic increases in Medicare spending on meds (see http://oig.hhs.gov/oei/reports/oei-02-16-00290.pdf ), with my commentary embedded in the major points:

• Medicare spending for Part D increased at $10 billion/yr from $51 in 2006 to $137 billion in 2015 (and $16 billion just from 2014-15).
  • One issue to me is that though Part D is a great help to many people (over 40 million beneficiaries in 2014), it was constructed by Bush to funnel the drug benefits through commercial pharmacies. And this is despite the fact that the feds have access to really cheap drugs (the cost of many generics to the feds is often about 1/100 that at the local pharmacies) and these vastly cheaper drugs are what millions of veterans already get through the VA system. To make things worse, the excessive cost of Part D leads to the “donut hole”, where after a few thousand dollars are spent on drugs, the federal subsidy decreases dramatically and many impoverished seniors are unable to afford continuing necessary medications
  • And, as we know only too well, there is no effective regulation on the price that drug companies charge, even for drugs they have been making for many decades (witness the huge increase in the cost of even the old insulins over the past decade, when the cost-of-living increased marginally)
• Spending on commonly abuse opioids was >$4 billion in 2015
• Spending on compounded drugs has increased dramatically
  • Overall Part D spending increased from $70 million in 2006 to $509 million in 2015, with the largest jump from 2014-15 (increase of $182 million)
  • Medicare spending for compounded topical drugs increased 3,466 percent since 2006, e.g. for the likes of lidocaine-prilocaine (local anesthetic) and topical diclofenac (anti-inflammatory).
  • Spending for compounded oral drugs increased 855 percent, IV drugs (e.g. parenteral nutrition and antibiotics) 333%, and other injectables by 285%
  • The availability of compounded drugs is important in several situations: a patient may need a liquid preparation of a commercially-available pill (trouble swallowing, etc.), or to eliminate an ingredient they are allergic to, or the drug is not available in a required form (e.g. injectable progesterone, used to help sustain a pregnancy in women with a threatened miscarriage; this had been available since the pre-FDA 1950s by compounding, but a (sleazy) drug company got a quick patent and increased the cost many-fold, and threatened the prior compounders with major lawsuits if they continued compounding it. See http://healthland.time.com/2011/03/10/can-patients-get-around-the-exorbitant-new-cost-of-a-pregnancy-drug/ which details some of the issues: the drug went from “around $10 per dose to $1500”)
  • Though, as we know from the recent compounding pharmacy fiascos, there does need to be some regulation to ensure against contamination as well as ensuring the potency of the drugs, with a couple of caveats here:
    • Compounders have worked for many decades without issues I’ve heard of. Some of the egregious issues with contamination seem to be more recent. ??why. ??decreased regulation ??increased drive for profits??
    • The role the FDA plays is not so clear to me. They openly state that their mission “is to ensure that drugs marketed in this country are safe and effective”, but they “do not test drugs” themselves (see http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ )
    • A couple of years ago I was interested to see what the FDA allowed as acceptable variability, e.g. when a drug company said “100 mg”. Was it +/- 2%, 10%, 50%??? I could find nothing printed, so I called them in Washington and actually spoke to someone there who said there was no general standard for brand-name or generic drugs. So, though the issue of potency is a real one, it seems that there is no acceptable variability standard overall, the FDA accepts what the drug companies say, and they do not regularly check for the accuracy of what they say…
  • “These trends raise concerns about fraud and abuse and patient safety”
    • The feds are pursuing some pharmacies that were paying kickbacks to physicians or to marketers for prescriptions, or they were filling prescriptions that should not have been filled

 

2. Another recent study looked at a different angle of drug company influence: how sponsoring meals for physicians is associated with preferential prescribing of brand name meds (see doi:10.1001/jamainternmed.2016.2765). Details:

• Cross-sectional analysis of industry payment data to physicians in the Medicare Part D prescriber file and prescribing data for individual physicians who wrote Medicare prescriptions
• Assessing 4 brand-name meds from 4 different classes:
  • Rosuvastatin (Crestor) vs other statins (rosuvastatin is the 3rd most costly drug in Medicare D, at $2.2 billion in 2013)
  • Nebivolol (Bystolic, Nebilet) vs other cardioselective b-blockers
  • Olmesartan (Benicar) vs other ACE/ARBs
  • Desvenlafaxine (Prestiq, Desfax) vs other SSRI/SNRI meds
• 279,669 physicians received 63,524 payments associated with these 4 drugs
• Physician characteristics: 70% male; 43% family or general practice/36% internal medicine/10% cardiology; 60% >20 years since graduation/38% 6-20 years; spread evenly through the US, but 85% urban; 22% of 2013 claims were written for brand-name drugs
• 95% of the payments were meals, with mean value <$20 (rest were from speaking fees, honoraria, travel expenses, free textbooks/etc. These were not included in the analysis)
• Those MDs accepting meals were less likely to have drug claims for low-income or Medicare Advantage beneficiaries
• Results:
  • Rosuvastatin comprised 8.8% of statin prescriptions
  • Nebivolol comprised 3.3% of cardioselective b-blockers
  • Olmesartan comprised 1.6% of ACE/ARBs
  • Desvenlafaxine comprised 0.6% of SSRI/SNRI meds
  • But, for physicians who received a single meal promoting the drug of interest, controlling for prescribing volume, specialty, practice setting and demographics (all p<0.001):
    • 18% higher use of rosuvastatin over other statins (1.18, CI 1.17-1.18)
    • 70% higher use of nebivolol over other b-blockers (1.70, CI 1.69-1.72)
    • 52% higher use of olmesartan over other ACE/ARBs (1.52, CI 1.51-1.53)
    • 118% higher use of desvenlafaxine over other SSRI/SNRIs (2.18, CI 2.13-2.23)
  • And, having more than one meal or having meals valued >$20 were associated with higher prescribing rates (true for all but desvenlafaxine, though the number of desvenlafaxine scripts was much less than the other meds), varying from 2-13% more if the meals were >$20)

 

Commentary:

• As a perspective, the amount of $$ paid by drug companies to MDs is huge (in last 5 months of 2013, 4.3 million drug company payments totaling $3.4 billion were made to more than 470,000 physicians and 1000 teaching hospitals)
• (but, I’m sure it was worth it to them, given the amount of $$ they make from the huge costs of the drugs as well as the undoubted tax write-offs for the expenses, if they deign to pay any taxes in the US)
• One confounder may be that MDs attending meals may be more open to writing for brand-name drugs (selection bias), though the researchers did look at those receiving a rosuvastatin-related meal, and those MDs did prescribe more brand-name desvenlafaxine, though with much smaller effect size than those getting a dexvenlafaxine-related meal; but not vice versa (getting a desvenlafaxine-related meal did not increase rosuvastatin scripts); however it would have been good to compare rosuvastatin scripts with b-blocker or ACE/ARB scripts, since they are both in the cardiologic realm. Another potential confounder is that MDs may preferentially attend meals for drugs they prefer.
• One old study that I remember (though do not have reference) asked doctors if they thought they were influenced by drug company “information”, with a pretty resounding response of “no”. Then the investigators asked the doctors what they knew about some of the newer drugs. And there was a pretty remarkable concordance between what the doctors said and what the drug company representatives said (as I remember, sometimes pretty much word-for-word). Rather striking how well we humans are able to rationalize almost anything…
• And, from the recent JAMA article, it was interesting that MDs could potentially have their prescribing patterns altered for a meal valued at $12-18….

For trove of drug company shenanigan articles, see https://stg-blogs.bmj.com/bmjebmspotlight/category/pharmacy/ , which reviews several different aspects of drug company malfeasance, from ghost-writing scientific articles (paroxetine), to suing the FDA to allow marketing of a triglyceride-lowering drug without an approved indication, to rebranding generics and dramatically increasing prices, to concealing adverse events from drugs and not revealing negative studies, to promoting a drug (dabigatran) but concealing important information which would undercut the “no need for blood monitoring” promotion, to huge profits from cancer drugs, to …..