Congress needs to reassess the US regulatory system for managing drugs. We have entered the era of personalized medicine where the biological traits of the individual can critically impact the efficacy of a drug regimen. Yet our system of approval is based on large clinical trials that presume a level of homogeneity among patients that may not exist. Furthermore, our laws are overly concerned with the risk of a drug but far less concerned with the benefits.
To make things worse, our labeling of drugs makes it almost impossible for a patient or a doctor to glean an understanding of whether to administer the drug. Patients worry about benefits (i.e., will this help me?). Regulators worry about risk (i.e., if we approve this drug will someone be harmed?). But, no one is doing the complex analysis to evaluate how a drug fits into our existing set of available drugs and treatment options.
The UK has a system in place that resolves some of these problems. The British have a subtle sense of humor. In the UK, the hot potato of telling the National Health Service (NHS) what they will pay for and what they won't is called "NICE" (National Institute for Health and Clinical Excellence). It is not part of the NHS, and it is not responsible for approving the sale of drugs, only the reimbursement.
In the US, the FDA approves a drug and then turns its back and lets the doctor solely prescribe it in anyway he feels appropriate. In the UK, drugs are approved for a specific disease endpoint. Furthermore, when NICE reviews a drug it does so not in a vacuum (i.e., drug A vs. a placebo). Instead NICE evaluates the drug as a possible alternative within the accepted and approved treatments for a particular disease endpoint (and the health economic implications.) This kind of analysis is an anathema to the way Americans feel their healthcare should work. But, there is a benefit to the NICE process beyond cost control.
As most of us know from personal experience, drugs are prescribed in two ways: acute or chronic regimen. The acute regimen is for drugs where a short dose solves the problem (i.e., steroid for poison ivy). Chronic regimens are doses that we take for long periods and often our entire life (e.g., statin, beta blocker, hormone replacement).
I want to focus entirely on chronic doses. This is where the drug companies make the most money and where the drug testing process has its greatest flaws. The largest flaw being that even if we test a drug for two years, the data cannot accurately predict what will happen to a population taking the drug for five years and across a wider breadth of human characteristics. This also uncovers a key point: All drugs have risks and benefits.
To compare the UK and US systems, I'd like to focus on a secondary treatment for diabetes: Avandia. Avandia is part of a class of drugs called Thiazolidinediones of which there are two competing drugs: Actos made by Takeda, and Avandia made by Glaxo Smith Kline (GSK). (They are not the same. A good comparison to keep in mind is that both Zocor and Lipitor are different statins, with often-different results, for treating cholesterol).
Avandia has received a great deal of negative press over the last few years:
•Sens. Max Baucus (D., Mont.) and Chuck Grassley (R., Iowa), released a new report last week on Avandia calling for the FDA to pull/cancel Avandia.
•An unpublished study by outspoken Avandia critic David Graham, an FDA drug-safety official, asserts Avandia is linked to increased heart attacks and strokes; similarly, the Cleveland Clinic's Steven Nissen, believes the same.
•GSK recently settled the first case in the U.S. to be brought to trial over claims that Avandia caused heart attacks and strokes.
All this pressure and press mean the FDA will review Avandia even though it has already had a black label (FDA's strongest labeling control) applied to the package to warn patients and doctors of side effects.
Now let's look at the NICE side of the same discussion. NICE has had two reviews of Avandia and Actos. The first in 2001; the second in 2009. Both reports go into excruciating details on when and how to prescribe either drug. Furthermore, it is clear from the studies cited, in particular Boyle et al that when heart attacks or strokes are a concern, Actos is the drug of choice.
The 2009 NICE report has pages of recommendations on treatment options based on different patient characteristics. None of these recommendations suggest using either drug as a primary treatment unless all else fails. These drugs are to be used in conjunction with other treatments. Furthermore, the 2009 NICE report emphasizes the importance of discussing risks and benefits with the patient.
Yet, NICE continues to recommend considering Avandia. Why? Perhaps neither drug works for every individual. Yes, Actos seems better. This point is emphasized by a 2009 article in the British Medical Journalthat states:
Among older patients with diabetes, Actos is associated with a significantly lower risk of heart failure and death than is Avandia. Given that Avandia lacks a distinct clinical advantage over Actos, continued use of Avandia may not be justified (US brand names added for ease of reading).
But these studies are all averages. In any specific situation Avandia might work better. It might save a patient. The key is informed medical decision-making on a case-by-case basis. It is this informed decision-making that seems to get lost in the FDA process.
FDA needs a sister organization like NICE to make sense out of the complex treatment questions that arise with the control of almost any chronic disease. Someone needs to ask: Who is helped by a drug? Otherwise, we are always faced with a zero-one situation: A drug is either approved or disapproved, and we must depend on the doctor having the time, inclination, and resources to delve into the literature and draw an informed, independent conclusion. This seems like a risky approach in today's world where doctors are forced to see more patients, receive lower reimbursements, and spend substantial time dealing with insurance companies.
If Grassley, Graham, Nissen, and the litigators are right, then why are doctors still using Avandia? The answer has to be either the system is broken and doctors are not aware of the potential problems or the doctors are seeing patient success. If they are seeing patient success, how does that get included in the decision-making? In either case, it appears the system needs fixing. My vote is for a NICE-type organization to augment the FDA.