Drug Approval Reciprocity

Shouldn't medical advances available in Germany be available in the United States and vice-versa?

pharmaceuticals

Daniel Klein and Alex Tabarrok argue that the slow approval process of the US Food and Drug Administration is extremely costly:

Medical drugs and devices cannot be marketed in the United States unless the U. S. Food and Drug Administration (FDA) grants specific approval. We argue that FDA control over drugs and devices has large and often overlooked costs that almost certainly exceed the benefits. We believe that FDA regulation of the medical industry has suppressed and delayed new drugs and devices, and has increased costs, with a net result of more morbidity and mortality. A large body of academic research has investigated the FDA and with unusual consensus has reached the same conclusion.

They offer a host of reform options, including removing barriers to consumer information, allowing access to drugs by seriously ill patients, and dropping the proof-of-efficacy requirement in favor of the previous safety-only approach. Most intriguing and obvious to me, though, is the implementation of international reciprocity.

If the United States and, say, Great Britain had drug-approval reciprocity, then drugs approved in Britain would gain immediate approval in the United States, and drugs approved in the United States would gain immediate approval in Great Britain. Some countries such as Australia and New Zealand already take into account U.S. approvals when making their own approval decisions. The U.S. government should establish reciprocity with countries that have a proven record of approving safe drugs—including most west European countries, Canada, Japan, and Australia. Such an arrangement would reduce delay and eliminate duplication and wasted resources. By relieving itself of having to review drugs already approved in partner countries, the FDA could review and investigate NDAs more quickly and thoroughly.

EU countries established a limited reciprocity system in 1983. Over time, however, the European system has evolved in a somewhat different direction. The reciprocity principle has two virtues, competition and elimination of duplication. Unfortunately, the EU has begun to subvert the first virtue (Hansen 2000). Today many products must be reviewed by the European Agency for the Evaluation of Medicinal Products (EMEA), headquartered in London. EMEA approval opens the market to all EU countries. Still, the EMEA regime is better than the FDA. For most drugs, the EMEA is not the sole source of authorization (hence, there is competition among the EU drug agencies); it contracts most of its reviews to outside experts; it takes a less adversarial posture; and it places more confidence in the sponsors ‘ summary reports (rather than reanalyzing the raw data) (Miller 2000). Nevertheless, there is little guarantee that the system will maintain its current performance, and, besides, being better than the FDA is nothing to brag about. If the EU centralizes authority, the vestiges of competitive governance might give way to monopoly governance.

International reciprocity would eliminate the FDA’s monopoly on drug approval. Under such a system, U.S. drug companies could submit the NDA equivalent to the authorities in partner countries and thereby gain approval in the United States. Thus, the FDA would have to compete for business. It would have to shape up or lose out on the fees that come with NDAs.

About a year and a half ago, I started noticing a deterioration in the vision of my left eye, especially while watching television at night. Having been nearsighted from childhood, which was finally corrected by LASIK surgery thirteen-plus years ago, I assumed that I needed a tune-up. It turned out that I had a cataract. My surgeon suggested that, if I were willing to wait a couple of months and were willing to pay a couple thousand dollars out of pocket, a revolutionary new lens that had been in use in Europe for years would be approved by the FDA. The expected approval didn’t come but we agreed to wait another six months. Still, no approval. Meanwhile, the cataract has gotten considerably more advanced and we’re in agreement that waiting around for the FDA no longer makes sense, so I’ll instead get the inferior lens installed later this month.

The absurdity of a lens that’s in widespread use in Sweden and Germany not being available in the United States because the FDA hasn’t gotten around to it is mindboggling. We’re not talking about a back alley in Tijuana or Marrakesh; these are at least comparably advanced countries. And, of course, the difference between a pretty decent cataract replacement lens and a very good one is nothing compared to, say, a vastly better heart valve or cancer drug.

Surely, pooling our combined knowledge is mutually beneficial. As Tabarrok observes at his blog, “If you lived in Great Britain or Germany and your physician prescribed a pharmaceutical, would you ask them, ‘has this pharmaceutical been approved by the U.S. FDA?’ Probably not.” Indeed; almost certainly not.

FILED UNDER: Bureaucracy, Health, World Politics
James Joyner
About James Joyner
James Joyner is Professor and Department Head of Security Studies at Marine Corps University's Command and Staff College and a nonresident senior fellow at the Scowcroft Center for Strategy and Security at the Atlantic Council. He's a former Army officer and Desert Storm vet. Views expressed here are his own. Follow James on Twitter @DrJJoyner.

Comments

  1. This has been an issue for a long time.

    When my Mom was first diagnosed with cancer in 1998, there was a test for Ovarian Cancer pending approval before the FDA. Six years later, it still hadn’t been approved. You also see similar problems with regard to approval of drugs that have already been approved for one use for an “off label” use.

    And, while it’s not entirely applicable to the point of the post, I’ve never quite understood why they apply the same stringent rules to drugs intended to treat, as a last resort, patients diagnosed as terminal that they do to something that might be prescribed for someone who’s generally healthy. Seriously, if the drug isn’t effective, what’s the harm in at least trying given that most of those terminal patients have nothing left to lose?

  2. James Joyner says:

    @Doug Mataconis: I get the basic idea of drug approval: we don’t want mass experimentation without stringent scientific controls. But, yes, it seems obvious that people in particularly emergent situations ought to be able to opt in to experimental treatments.

    What intrigues me about the reciprocity issue, though, is that it’s even more of a no-brainer: If other advanced countries have approved the drug, it’s AN APPROVED DRUG, not merely an experiment. It’s not like the governments in London, Paris, and Berlin are less competent or cavalier with the lives of their citizens that ours.

  3. michael reynolds says:

    There’s always the Thalidomide example, unfortunately. Still, I agree. Treatments developed and tested in reliable countries should be fast-tracked.

  4. michael reynolds says:

    By the way, you’ll notice that I was very mature in not making a crack about your inability to see anything on the left clearly.

  5. @James Joyner:

    Agreed. I get the idea of not taking the drug approval processes of less advanced countries, if they even exist, seriously. However, if the appropriate authorities in Europe, or Japan, or Australia have approved a drug it strikes me that the FDA ought to be considering that and reviewing their studies rather than, needlessly and at great cost, trying to reinvent the wheel.

  6. stonetools says:

    Thalidomide was a drug originally introduced and approved for general use in Germany. See why Germany might not make a good case for drug reciprocity?

    PS. Michael beat me to it.

  7. Gustopher says:

    I would fear that if we started down that path, reciprocity of drug and medical device approval would become just another trade issue. Germany and Switzerland, sure, but what about Greece, Italy, Korea or China? I suspect the Greeks, Italians, Koreans and Chinese would want in on this, and it would become a negotiating point in trade agreements. Is it an affront to the Russians that we don’t trust their approval process when we trust the Swiss?

    The problem with “competition” among regulatory agencies is that it quickly becomes a race to the bottom to provide the minimum protection for consumers. Pharmaceutical companies will shop around for the laxest approval process.

    I’m all for streamlining the current process, taking foreign studies and approval into account, and actually funding the FDA to a level where it can act quicker, but we really shouldn’t be ceding our authority to approve drugs.

  8. @michael reynolds:

    Of course that was in era when drug testing was not as thorough as it is today. And, today Thalidomide is being used as a cancer drug

  9. @Gustopher:

    Instead of an FDA policy that said “if it’s approved in Country X, we’ll approve it,” perhaps the better way to handle this would be for the agency to consider approval in other advanced nations with rigorous testing regimes as persuasive evidence in favor of approval along with the results of its own required testing.

  10. steve says:

    It is not just the drug or device, but how it is used. For example, Lovenox was used quite successfully in Europe. When it came here, we ended up paralyzing dozens of people. I think you also need to remember that European countries are subject to special interests just like we are. A drug approved in Europe due to lobbying there, may not be appropriate here.

    That said, I think that in general we should fast track drugs approved in the EU and other places with quality care. I would also be skeptical about claims of some new, revolutionary lens. Every medical device ever invented is going to be revolutionary. Most are gone in months or end up being little different than the old devices.

    Steve

  11. Andre Kenji says:

    @michael reynolds:

    There’s always the Thalidomide example, unfortunately.

    I thought the same thing after reading the TITLE of this post.

  12. legion says:

    The problem with this proposal is that there are a veritable sh*t-ton of assumptions being made in terms of what an “advanced” country is, what sorts of standards those countries have, and how the eventual legislation might respond if one of those countries stops being so reliably “advanced”.

    Also, just because the US considers countries X, Y, and Z sufficiently advanced that we can “take their word” on drug safety, there’s no mechanism for determining or enforcing what _those countries_ consider “advanced enough”. Here’s what I mean – let’s say we trust the UK. The UK trusts Germany. Germany trusts Turkey, and Turkey trusts Sri Lanka. All a pharma company has to do is get its meds approved – by hook or by crook – in Sri Lanka, and boom! instant approval all the way up the chain. And all the company has to do get approval – somehow – from some non-G8 country whose annual GDP is probably smaller than the CEO’s monthly salary.

  13. Andre Kenji says:

    There are additional problems. In the US, there is the understanding that supplements are food, not medication, and in most countries there is no such understanding(I know, because as weightlifting fanatic that does not live in the US there are several supplements that are freely advertised in the US, but that I can´t legally buy). There are differences of culture and differences of what could be understood as a risk.

  14. anjin-san says:

    The Thalidomide tragedy took place half a century ago. It’s a cautionary tale to be sure, but I doubt that it is relevant to today’s world.

  15. steve s says:

    Thus, the FDA would have to compete for business. It would have to shape up or lose out on the fees that come with NDAs.

    You know who were really competitive about ratings fees? Moody’s, Standard and Poor’s, and Fitch.

  16. john personna says:

    @Doug Mataconis:

    A cancer drug is vastly different in risk profile (and of course frequency of application) than a morning sickness drug. Enough so that Thalidomide as a cancer drug is completely separate from the failure of testing in a morning sickness role.

    … on that though, and why the Thalidomide example fits so much in our minds, I think it is because we have a great aversion to killing the healthy (the merely morning sick). We want a lot of US FDA testing so that we won’t be killed “like they do” elsewhere.

    That doesn’t always produce a rational analysis. If we saved 10 in new drug applications for every 1 we killed in side effects it would be a triumph in the utilitarian view … but I don’t think anyone is really that unemotional about it. (Or we picture ourselves as the 1 rather than as one of the 10.)

  17. rudderpedals says:

    I’ll instead get the inferior lens installed later this month

    Why not fly to Germany or Sweden and have the procedure done there?

  18. Crusty Dem says:

    For all the time and expense, our drug approval process is far from perfectly safe, a number of drugs with serious, deadly side effects have been approved in the last few years (just dial 1-800-BAD-DRUG, right?). I know many doctors won’t prescribe new drugs for non-life-threatening conditions, referring to a recently approved drug as a “stage 4 clinical trial”.

    In reality, a drug or implant approved and used in another country may not be perfect, but is probably safer than a new drug passing US stage 3 clinical trials.. I would at least recommend granting any approved drug from a first world country fast track stage 3 trial access, but reciprocity with some countries would be very beneficial..

  19. flyfish says:

    Medical tourism is becoming more prevelent all the time.

  20. MarkedMan says:

    This is a long post, bu since I’m in the Medical Device industry, I may be able to add clarity here. What I say applies to devices; I don’t know if it applies to drugs. The biggest difference between Europe and the US is that to release in Europe you must demonstrate that you are safe, while to release in the US a device must be proven “safe and effective”. This is no small difference. Although my company and others routinely release in Europe first because the process is faster, this amounts to a few months and the Europeans get the benefit of the “and effective” part because we already know we have the data to show effectiveness before we start the process. And this effectiveness is no small thing. Despite the hype that surround new drugs and devices, most are at best incremental improvements. (I just deleted a boat load of minutia surrounding this area – suffice it to say this is a generalization but is basically correct).

    So 1) Right now devices released in the US must prove they are effective and not just safe; 2) Any device from a major, reputable producer that is released in Europe will also be released in the US so Europe benefits from the “effectiveness” part of the US law – and this means that it is meaningless to say ‘Europe doesn’t have effectiveness clause but still has good outcomes’ because essentially they do have it; 3) Personally, if I found out a device was only released in Europe and was not intended for US release, I would be extremely reluctant to have it used in or on me or my loved ones.

    Finally, despite our caution, bad things get approved, like the metal on metal knee implants, or the faulty pacemakers in the news. When that happens, FDA members will get dragged in front of congress and humiliated, primarily by Republicans, who will also demand some heads. Those officials will be unable to offer any real defense because their role is to serve as a punching bag and any deviation from that role jeopardizes funding for their agency. Republicans hold all government officials in absolute contempt and will come after them for not approving and then come after them when they do approve. So calls for “reform” are, correctly, viewed very cynically by those same officials.

  21. @Doug Mataconis:

    I’ve never quite understood why they apply the same stringent rules to drugs intended to treat, as a last resort, patients diagnosed as terminal that they do to something that might be prescribed for someone who’s generally healthy.

    Because of the ethics of doing medical experimentation on people that would take a drug if it has a 1% success rate even if it has a 50% fatality rate?

  22. OzarkHillbilly says:

    competitive governance

    You have got to be F’n kidding me.

    Surely, pooling our combined knowledge is mutually beneficial.

    True but….

    “If you lived in Great Britain or Germany and your physician prescribed a pharmaceutical, would you ask them, ‘has this pharmaceutical been approved by the U.S. FDA?’ Probably not.” Indeed; almost certainly not.

    I don’t live in Germany or the UK. So why in FSMs name would I ask ‘has this pharmaceutical been approved by the EMEA?’

    @Doug Mataconis:

    And, while it’s not entirely applicable to the point of the post, I’ve never quite understood why they apply the same stringent rules to drugs intended to treat, as a last resort, patients diagnosed as terminal that they do to something that might be prescribed for someone who’s generally healthy.

    Because people with terminal illnesses have a tendency to be desperate… And ripe for a good fleecing.

  23. Rob in CT says:

    Instead of an FDA policy that said “if it’s approved in Country X, we’ll approve it,” perhaps the better way to handle this would be for the agency to consider approval in other advanced nations with rigorous testing regimes as persuasive evidence in favor of approval along with the results of its own required testing.

    This seems reasonable.

  24. Ebenezer_Arvigenius says:

    It should also be noted that the Thalidomide case is not indicative either way. In 1954 teratology testing was – to my knowledge – not mandatory anywhere in the world. In fact the U.S. developmental and reproductive toxicity testing guidelines were established in 1966 as an answer to the Thalidomide scandal.

    The U.S. were spared negative effects not because of superior testing (In fact, the case was assigned to the freshly hired Frances Kelsey as a good and easy introductory project for a newbie.) but because Richardson-Merrell refused to provide any scientific data on the drug when applying for FDA approval in late 1960 (they wanted to have the drug in the market before Christmas). Instead they tried to apply political pressure on the FDA.

    By the end of 1961 (and before the FDA had even reviewed the drug) the first studies on the use of the drug on humans had been conducted and the previously undetected effects had been documented in Germany, the UK and Australia by Widukind Lenz et. al. leading Richardson-Merrell to withdraw the application in 1962.

    So the problem was not caught by FDA testing but – unfortunately – by its adverse effects “in the wild”. The FDA never conducted an actual review in the true sense.

  25. MarkedMan says:

    You know, the cataract thing is curious. When we file for a device in Europe and the US, we use the same data to justify. And the lens is a device, so my experience should be at least generally applicable. So I wonder why they are not releasing in the US? Are they not submitting? If so it could be trouble with effectiveness, or problems showing up in the field. Or, if they did submit, it could be that the FDA just raised more questions than under the CE process.

  26. Ebenezer_Arvigenius says:

    So I wonder why they are not releasing in the US? Are they not submitting?

    Most likely a timing issue. CE certification is on average between two and four years faster than FDA approval.

  27. MarkedMan says:

    @Ebenezer_Arvigenius: Interesting. Is that 2-4 years specifically for cataract lenses? Because for the two medical device industries I’ve been involved with it is typically a few months, not a few years. Of course, we prepare both filings at the same time. But for a routine release, from the date all the work is done to the time it is approved in the US it is usually less than 6 months.

  28. MarkedMan says:

    One thing that can make a big difference is if the device is similar to one in the past, i.e. there is a “predicate device”. If a device is completely new, such as, I don’t know, a device that uses electrical pulses to realign bones, it must go through a lengthy and very thorough long term study to show safety. If it is a variation of a similar device, and I would imagine a new cataract lens fits into that category, the process falls under the 510K provision and is much shorter.