How to Get Rich – A Guide for Pharmaceutical Companies

The Changling Ming Dynasty Tomb of the Yongle Emperor
The Changling Ming Dynasty Tomb of the Yongle Emperor – copyright 2012 Daniel Ginsberg Photography

Thanks to Congress, Medicare is not allowed to negotiate for the cost of medications. The bill was shepherded through by congressman Tauzin, the chairman of the House Energy and Commerce Committee that regulates the industry, who subsequently stepped down then took a job as the President and CEO of the Pharmaceutical Research and Manufacturers of America. This is a lobbyist group for pharmaceutical companies.

Here’s a suggestion to pharmaceutical companies; the next time you come out with a new first in class medication, for which there are no other medications that can be substituted, price it at 10 billion dollars a month. After the first prescription gets filled, it may move Congress to act, but by then you will be set and it won’t matter if you don’t sell another pill.

Medication Small Print

WhenSolu-Medrol_crop I give a cortisone injection, I have to document it in our electronic medical records. I’ve always included the dose, how administered (intramuscular), and the lot number. This week my company added the requirement that we include the NDC number, as insurance companies wanted the information.

It’s just one more administrative requirement, but what really makes it bad is trying to read the number off the bottle. As you can see from the photo, the font is very small! I suggested the policy was age discrimination, but that didn’t get far.

PhRMA Two-Step Dance

As part of my practice I conduct research studies for pharmaceutical companies. In order to get medications approved by the Food and Drug Administration, companies need to do studies to prove the medications are safe and effective. Studies are often conducted by multiple physicians around the world in order to get a sufficient number of patients, and to help them get the drugs approved in many countries.

The kinds of studies I do are mostly big and fairly complex endeavors. They usually have an investigator meeting prior to starting in order to explain the study, how to enroll patients, ship blood samples, order supplies, and many other details. It’s also a chance to ask questions and meet others involved in the study.

Pharmaceutical companies pay a certain amount of money to each practice for helping them do a study. That money is used for a number of things, including paying for staffing, and usually a small stipend to patients to cover their transportation and time. The budget includes money for investigators, such as myself, to attend investigator’s meetings, but unless it’s a local meeting, I make less money than I would just seeing patients in my office. A trip to the East coast takes about 3 days including the travel time each way, but I only get paid for the one day. It’s a nice change of pace, though, and it’s fun if I get to go to a city I’ve never been to before, or enjoy visiting.

Recently I was invited for the first time to an international meeting, in Vienna, Austria, by Novo Nordisk. I’d never been there so I figured I’d go a few days early to see the city. I called to book my flight but was told I could only travel the day before the meeting and return the evening of the meeting, or at most the next day. I explained that I intended to pay for the extra hotel nights and food expense, and it wouldn’t cost them any additional money. They said that they could not because of PhRMA guidelines which I’ve discussed before. They said if I arrived early they would not pay for my flight there. The concern was that they would violate the guidelines because if I spent more time at the destination than necessary, they would essentially be paying for a vacation. I pointed out that arriving early would be to their benefit as I’d be less jet lagged while attending the meeting. I also said that if I was taking a vacation, I would bring along my wife, stay for a couple of weeks if going that far, and I wouldn’t visit Vienna in the middle of the winter.

Going to Vienna I want to waltz, but PhRMA wants me to do the two-step, straight there and back. Well I have better things to do with my life, so they will need to find another dance partner.

Over-the-Counter Confusion

Over-the-(sushi)-counterThe FDA allows some medications to be sold over-the-counter (OTC), generally after patent expiration. Pharmaceutical companies need to prove they are safe to be taken that way. But as more medications become available, the opportunities for confusion increase. I’ve had patients confuse Zantac and Zyrtec. The first is for acid reflux and the second is for allergies. Even if drugs have similar names, a pharmacist usually catches the difference due to the dose written on the prescription. For example, Zantac comes in 75 mg, 150 mg and 300 mg, but Zyrtec is 10 mg. The typical lay person doesn’t know what dosages medications are supposed to be. They just (hopefully) know how many pills to take. So if they don’t read the label, they may take the wrong medication due to getting the names confused.

Anti-inflammatory pain medications are particularly a problem. There are OTC versions (Advil, Motrin, Aleve, etc.) and prescription dose strength versions of those, as well others that do not have a generic version. This class of medications is called non-steroid anti-inflammatory drugs (NSAIDS), and usually people should not take more than one at a time. But not uncommonly I see patients take a prescription one plus an OTC one, not realizing they are similar medications. By doing this you get very little additional benefit, but more risk of side effects.

If you use OTC products, be careful to read the labels carefully. If you are taking prescription medications for the same purpose, or you have any of the conditions they warn you about on the label, check with your physician first.

Dinners and the Sunshine Law

Though implementation has been delayed until 2013, per the Sunshine Law, pharmaceutical companies are now collecting information to report to a public website the value of things they give to physicians, including such things as dinner meetings. It may sound like doctors are just being wined and dined to get them to prescribe their medications, but as I’ve said before, there is value in such dinners.

For example, I went to a local dinner meeting early this year, featuring a speaker who was an expert on hypertension. Sure the meal was free, but not such a bargain when you considered that my wife could not attend, it was with people I might not necessarily have chosen to dine with, and despite a long day at the office, this expert was talking about medicine before I could even look at the menu.

But it was worth it because I learned some valuable information. As a result of hearing him talk, one change I made was to more often start giving at least one blood pressure medication at night because he said it would help prevent early morning strokes and heart attacks. After that meeting I later saw an article confirming the value. Had I not attended the talk I might have eventually changed my prescribing habits, but I changed it sooner as a result. In fact studies have shown it usually takes ten years for doctors to incorporate new medical information into their practice.

The pharmaceutical company that sponsored that dinner has a blood pressure medicine that I use some, but frankly not that much, and it has not increased since that dinner meeting. But perhaps I saved a life as a result of knowledge gained from that meeting.

Ask the Doc: Human Growth Hormone

On this site I’m unable to answer patient specific questions, but as time permits, may answer questions of a general interest.

Question:

I have been working out with a personal trainer with weight training and have been doing running on my own. I have been getting much stronger although I haven’t lost much weight. I asked the trainer why it takes longer to recover from a strenuous session at age 66 than it did when I was younger. She said that as we get older we have very little HGH in our system and that a small dose of HGH would help me recover quicker and she could push me harder. Would a small dose of HGH be beneficial for training? I know that testosterone creams etc. have a lot of side effects which are not good but how about HGH?

Answer:

Human Growth Hormone, or HGH, is a hormone that regulates growth, and decreases with age, as well as from obesity. It is one of many factors why, all other things equal,  66-year-olds aren’t as strong or fast, or recover as quickly, as when they were younger. With age lung function gradually declines, the cardiovascular system is less robust, testosterone levels fall in men, etc. In one of his movies, Warren Miller said something like, “If a 40-year-old says they sky as well as when they were 20, they are either lying, or they weren’t very good when they were 20!”

Human Growth Hormone is only approved by the FDA in limited circumstances, not including the normal decline with aging, and it’s expensive. It probably does build muscle, and for this reason is banned by the Olympics and some other sports institutions. It also has potential side effects.

Getting adequate sleep, regular exercise, eating healthy, and managing stress, are the most important things you can do to boost your growth hormone and improve your endurance.

American College of Physicians Internal Medicine 2012

I recently attended the American College of Physicians (ACP) Internal Medicine 2012 annual meeting, held this year in New Orleans. It’s a very large meeting with thousands of physicians attending. At any one time there are dozens of courses one can attend. I try to balance learning about subjects I have a particular interest in, with those that I’m less interested, and consequently have more to learn.

Among the talks I attended was a talk on genetics issues in internal medicine by Matthew Taylor, MD, PhD.  He discussed an interesting case of a 19-year-old woman who had been in good health who had lifted weights, used a hot tub then went swimming in a lap pool and was found unresponsive in 4 feet of water in 1998. She was resuscitated but died in the hospital 12 days later. An EKG done during the hospitalization was mildly abnormal with a prolonged QT interval. This was dismissed by most cardiologists as probably or not significant when asked to review the EKG. A subsequent genetic analysis of autopsy material revealed a genetic condition associated with a prolonged QT interval, which itself increases the risk of sudden death due to an arrhythmia. Further testing showed her sister, mother and maternal grandfather were found to have the same genetic condition. Most physicians would not even consider a genetic condition as the cause of a drowning, yet making the diagnosis may prevent family members from dying due to an arrhythmia with appropriate treatment.

I attended a talk by Holly Holmes, MD on discontinuing medications. It’s much easier to start a medicine than to stop one, yet medications carry financial costs and may cause side effects. She went over some cases and discussed strategies to decrease medication use. Amusingly she pointed out that not only did she not have any financial disclosures that might cause a conflict of interest, but that no pharmaceutical company would want to pay her to recommend stopping medications!

Besides the vast number of courses, there were also hundreds of vendors from pharmaceutical companies discussing new medications, companies selling books, equipment, massage chairs and gluten free products, and many just providing free information. There were recruiters looking for doctors, and more.

There was also the opportunity to interact with colleagues from around the world. I spoke with some physicians in Canada, and one from Saudi Arabia. I usually attend the ACP national meetings every few years and always come away having learning things that will help my patients, and feeling more invigorated about my profession.

Drug Shortages and the Joint Commission Stance

Periodically there have been drug shortages in the United States, which comes as a surprise to many. There are a number of reasons for this.

Recently one of my company’s pharmacists informed the physicians in my group of a nationwide shortage of bupivicaine and lidocaine, medications used for anesthesia, similar to what your dentist may give you before drilling your tooth.

I suggested that maybe we should be allowed to use such products past the expiration date until the shortage was resolved. They replied that they can’t do that because of Joint Commission standards.

So I wrote to the Joint Commission and eventually spoke with a nurse there. Their position was that it’s not safe to use a drug past its expiration date and they were just following guidelines by the Food and Drug Administration and others. I said that although I would generally agree that it is preferable not to use expired medications, in the case of shortages that may not be the case.

Imagine you have a life threatening infection with a bacterial organism resistant to all antibiotics but one, and there is a shortage of that antibiotic. In fact the hospital you are in has a box of antibiotics that expires at midnight tonight. They can give you only one dose then will have to throw away the rest, even though antibiotics would normally be given for 10 days and they don’t know when they will be able to get more.

Are you really safer as a result of throwing away the rest of the vials of the only antibiotic to treat your infection? In the interest of fair and balanced discussion I admit that I’ve eaten tuna fish after the date stamped on the can. But seriously, the risk of a complication from a slightly outdated medication is almost non-existent, and certainly less than the risk of going without.

Physicians going on medical missions to third world countries used to bring with them expired medications to administer to patients, the thought being that they were safe and better than nothing. Due to liability concerns, that pretty much doesn’t happen anymore, a fact said Joint Commission nurse brought up. In fact a 1997 article in the New England Journal of Medicine pointed out that at least half of the drugs donated to the Bosnian conflict were unusable because they had expired, and said pharmaceutical companies may have dumped the medications to get tax write offs and avoid disposal costs. That may have been the case, and could be addressed by not granting write offs for expired drugs, but that doesn’t mean they couldn’t have safely used the medications.

A 1979 law required pharmaceutical companies to give a date they guarantee the full potency and safety of a drug. They stand to gain financially when customers throw away good medicine because it has, “expired”. In fact the military conducted a study to see if they could extend how long they keep medications in order to cut back on the cost of destroying and replacing a billion dollars of inventory every 2-3 years. They found that 90% of the more than 100 drugs they tested were safe and effective up to 15 years after the expiration date. This program is now used by the Department of Defense, the Department of Veteran Affairs, the US Postal Service and the Bureau of Federal Prisons.

The nurse at the Joint Commission pointed out that I could decide whether the risk was warranted to use an expired drug. But in reality, I don’t get the chance to even discuss it with a patient to give them a choice. Hospitals risk a large financial penalty, and potentially even being shut down, for violating Joint Commission standards. Those drugs are going to go in the trash the day before they expire, shortage or no shortage.

I think the Joint Commission should modify their standards. At the least it should say that drugs should not be used after the expiration date unless their are shortages, or delivery problems due to disaster, in which case the medications should only be used if there are not suitable alternatives, and it’s felt that the benefits exceed the risks.

Limiting Medication, But Not Really

Once again, CVS Caremark wasted my time. On 1/27/12 they sent me a copy of a letter they sent my patient saying they only provided a limited supply of tramadol to my patient because it’s subject to plan quantity limits. The directions I wrote said that she could take up to 8 pills per day. I only wrote for 60 pills, though, so I didn’t understand why the letter.

It took me about 10 minutes, but a customer representative said I could have ordered 240 pills at a time and it should have gone through. He didn’t know why the letter went out. I pointed out that besides the fact that his company wasted paper and postage mailing out the letters, it probably caused my patient to be concerned, and it wasted my time. He apologized and said the coverage should not be a problem. I said that surely this wasn’t the only mistaken letter they’ve sent out and said he should pass this on to his supervisor.

Mistakes happen, but the answer should not be, as Gilda Radner said, “Never mind!” Instead organizations should apologize and try to figure out why it happened, and what can be done to prevent it from happening in the future. When a pharmacy benefit manager, such as CVS Caremark, does otherwise, the message is they don’t care if they waste doctor’s time.

Acid Revelations – Acid Reducers and Asthma in Children

The Journal of the Medical Association recently published an article about the use of lansoprazole (Prevacid) for children with poorly controlled asthma. It had been thought that gastoesophageal reflux disease (GERD) contributed to asthma exacerbations because acid would come up from the stomach and get into the lungs.

By putting tubes down the nose and into the stomach and esophagus it was known that children often have reflux when they have breathing problems, even without having heartburn symptoms. Proton pump inhibitors (PPI’s) such as lansoprazole, omeprazole (Prilosec), pantoprazole (Protonix) and others, markedly decrease the amount of acid produced in the stomach. Even if the contents reflux into the esophagus (think of an old fashioned coffee percolator), there would be less irritation if it was less acidic.

In adults with asthma and reflux symptoms, studies have shown the PPI’s help their lung function. Despite lack of conclusive studies showing benefits in children, its use in them markedly increased between 2000 and 2005. It made intuitive sense and the medications seemed pretty safe.

In this study children with poorly controlled asthma without gastroesophageal reflux (GER) symptoms not only did not do better with lansoprazole, they had more adverse events with increased respiratory infections. There were also six times as many activity related fractures in those on the medication. Although it didn’t quite reach statistical significance because of the relatively small numbers, the PPI’s are known to be associated with osteoporosis in adults.

This illustrates the important difference in statistics between association and causation. Just because two things occur together, doesn’t meant that one causes the other, and even so, it doesn’t mean treating one will treat the other. There is an old joke of a man walking around carrying an umbrella on a sunny day. “Why are you carrying an umbrella when it’s not raining,” asked his friend. “To keep the tigers away,” he replied. “But there are no tigers around here,” his friend objected. “See, it works,” he answered.

The accompanying JAMA editorial called the use of proton pump inhibitors for asthma a case of, “therapeutic creep.” That’s using medications beyond what the scientific evidence shows. This is not necessarily wrong. For example I commonly recommend vitamin D for my patients even though we still don’t have definitive evidence. In such cases, though, it’s good to remember the limits of what we know and beware of potential risks. As Hippocrates reportedly first said, Primum non nocere – First do no harm.

Even my dog’s veterinarian suggested using using over-the-counter Zantac or Pepcid for reflux because my dog sometimes threw up on the rug. Now I don’t feel so bad that I ignored her advice.