The Laughing Wolf

Some Thoughts On Merck, Drugs, and Medicine

I’ve been meaning to post on this for a while, but real life has intervened. Net result, this will not be quite as detailed and link-rich (just go read the last two weeks over at Galen's Log for goodposts on Merck and on the vaccine issue) as I would like, but will provide a good starting place for research and thought.

Yes, I am one of the ones effected by Vioxx and its recall. The extent to which I will be affected remains to be seen: it may be simply the loss of a drug that worked well on me. As for how I feel, the jury is out because there simply is not enough information yet available to form a reasonable opinion. There are claims made that Merck has long known of the heart problems, and there are equally compelling claims that they did not. The truly important point is, alas, getting lost in the finger pointing and the lining up of lawyers at the potential trough. The important point is that we had a drug in the first place.

I have lost count of the number of people I have met who appear to think that pharmaceutical companies dream up a drug, make a sample, take it to the FDA for easy approval, and then put it on the market. Depending on who you talk to, this is either straightforward or accompanied by bribes, hiding of bad results, and more. You pays your money and you take your distorted reality. Then there are others who feel that the problem lies in the big drug companies, that they are to blame. The fact is, under our current system, there would be no drugs without those big companies because the system demands them.

Yes, a small company can develop the idea for a new drug and even do all the research on it. Such can be done for a reasonable amount, provided you consider tens to hundreds of millions of dollars reasonable. Modern drugs are not made by random combinations of compounds or brews, or even trial and error, as has been the case in the past. Today, companies use combinatorial chemistry, structure-based drug design, and genetics to develop drugs that are targeted and effective. Drugs that affect the entire system are not desired, because of side effects. Instead, what the companies (and patients) want are drugs that target a specific site or area and only that area – with the result of very effective treatment with few or no side effects. We are still not there yet, but that is the direction research is pursuing.

Genomics, protein crystallography, and other delights take facilities, researchers, and even access to esoteric things such particle accelerators. Some of that is very reasonable in cost, others are quite expensive. To develop a new drug requires a good bit of R&D expenditure.

Let’s say that a small company does this. They have developed a new drug that will meet a need, have gotten the funding to do the R&D, spent the months/years required for this, and have developed it. Now, you have to go through the FDA approval process. According to published information, the FDA process takes 5-7 years and average costs that are reported as being $500-$800 million dollars. This is per drug people, and if part way through you develop an improved version of the drug, go back, do not pass go, and start all over again. Not many small companies can afford to do this, so it takes the resources of the big pharmaceutical corporations to pay for it; to deal with the massive amount of FDA paperwork that has to be filled out just so and filed just when and while hopping on the right foot; and, to cover against litigation.

Litigation will come, because the FDA and a gullible public tout risk-free medicine. One size fits all, no risk, and no consequences. When the inevitable happens and there is a bad reaction or a death, the lawyers will swarm and the shout will go out that “They should have known!” How they should have known is the mystery, and one that the lawyers and others who get rich off the process would not like you to solve, for doing so would expose the fallacy.

The fact is, there is no such thing as a risk-free drug. The FDA testing and approval process does weed out most of the obvious problems, but the samples are limited. They have to be to get through the process, and this is going to only get worse as the system tries harder to ensure zero-risk. This means that when the drug in question hits a larger sample of population, things are going to pop up. That is a statistical certainty upon which you can bank. You also need to factor in effects that will show up over time, for there are things that may not show up until you do a large sample over a 20-30 year time-frame. Will they be statistically significant? Hopefully not, but yet and still they will be there. Covering against them costs yet more money. I am not even going to go into production, marketing, delivery, and other things, for the point is made.

The net result is that you have to spend towards $1 billion per each variant of a major drug to get it to market. Some are going to cost more, and some may cost much less, but yet and still it is not pocket change. It is a massive undertaking of time and money.

Now, there is one more cost to factor in to the equation: the human cost. While the drugs are in development and then clinical trials, they are not available to those that need them most. There is a drug that may cure your significant other, keep them alive and enjoying life. What if they can’t get that drug, but are told that they must wait until all the hoops are jumped, paperwork filed, and as close to zero-risk to them is assured. There are people that face that every day. The government is not going to let them take it until procedures are complete, and the companies can’t afford to let them take it because even if they die from something else, it still is a negative impact on the drug and the drug studies. Even if it gives your SO months of living, the fact that your SO died can prevent the drug from reaching the market. All of the money put in by investors and the companies involved then goes down the toilet.

That, in a very rough and incomplete nutshell, is the system we have. That it works is nothing short of miraculous; that it could be better is beyond doubt. Just how it should work better is the question. There are those who argue that it should move even more to the zero-risk option, ignoring the fact that it will also effectively end pharmaceutical development in the United States. There are those who argue that there should be no approval process, also ignoring the fact that it would effectively destroy pharmaceutical development in the United States. What we need is an improved process that helps guarantee safety to a reasonable degree, and, more importantly, gives patients the option of taking risks. Imagine if you will, that there was a drug that could deal with a particular terminal illness and let you live (as opposed to existing). This drug, however, has some side effects or the potential for serious side effects later in life. Under current rules of approval, and more importantly the rules of litigation, you don’t have the option of taking it. I would like to have the option of working with my doctor to decide if I wanted to take it even knowing the side effects.

The keys to this are dealing with the litigation issues, the regulatory hurdles, and public education. It would demand both an informed user and an informed producer, but would the results not be worth it? Wouldn’t it be great if we could get the system so that more small companies (who provide the greatest amount of innovation and economic growth) could do this themselves, and have the chance to become big companies/corporations if they so desire? Wouldn’t it be great if we could get many more effective and safe drugs to market sooner, or to the patients who need them even as the process grinds on?

Also, as a final bit of food for thought, when you scream next time at the cost of drugs, take a breath and think instead. Look at the total cost of what went into that drug, and you may not scream as much. Think about the drugs that deal with diseases that are nasty, but few people have, and how much it costs to develop them. Then think a bit about how companies can make that money back (plus a bit for themselves), for they sure can’t do it by charging the real cost of the medicine to such a small group. Ever stop to think that the reason a “simple” drug used by so many costs so much might just be so that somebody somewhere with a rare disease can be treated, rather than it just being thievery on the part of the drug company?

The system isn’t perfect, nor any of the players. There is blame to go around, and praise too. For the miracle is that the system works at all.

LW