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Clinical Trials

Not How You Speed the Process Up, Exactly

Now, this truly does not sound like the way to run a clinical trial. Dr. William Halford of the Rational Vaccines company invited 20 patients to St. Kitts for a trial of a putative herpes vaccine. The consent forms explicitly stated that this was done to evade the jurisdiction of the US Food and Drug Administration, and so he did. According to the Kaiser Health News, no one knows where the vaccine was manufactured or how. There was no review board oversight. And Halford gave booster shots (whose content and provenance is likewise uncertain) to patients after they arrived back in the US.

Normally, this sort of thing would be inviting prosecution. But Dr. Halford died last summer, of cancer that was diagnosed back in 2011. He seems to have decided to break loose of regulatory boundaries in his herpes vaccine work around that time, self-experimenting with several variants of his vaccine ideas. Some of the patients reported side effects from the treatment, but it’s not like we have any detailed records of such things, because Halford doesn’t appear to have kept any. He did try to publish a manuscript on the whole effort in Future Virology, but the review process did not go well, as you might imagine:

4. The author presents results of 2 experiments on humans, the first one a safety study that he  conducted on himself. While self-experiments are generally permitted, these still require IRB review. Please provide assurance that this protocol was IRB reviewed and that the participant signed an informed consent. Unfortunately, data on 1 person does not prove safety of a product.

5.  The subsequent Phase 1 study was conducted on a Caribbean island nation. Again, no  information about IRB for this study is provided, and the trial does not seem to be listed on The data on efficacy are based on self-report on participants who were questioned by the author and other staff before and after. As the author states, “self-reported cessation of genital herpes. . .should be viewed with skepticism. Agreed.

6.  On Figure 8, there is an impressively small p value. However, how it was derived is not shown. Given that there were only 17 persons in this study, it is unlikely that an appropirate statistical test was performed to obtain this result.

Back in April, Halford and his associates press-released an investment in Rational Vaccines by Peter Thiel’s investment fund. That has generated a lot of headlines about “Peter Thiel funds illegal human trial!” and so on, but (as much as I’m skeptical about his pharma ideas), this coverage is unfair. The investment occurred after the offshore trial had already taken place, and in fact, Thiel’s people insisted that further work on the vaccine be done in a more, well, rational manner. According to the co-founder of the company, Agustin Fernandez:

But (Fernandez) said that this past spring — about six months after the first trial was concluded — when Halford and he met with Thiel’s representative to discuss Thiel investing in the vaccine’s development, the representative “yelled” at Halford for arguing that his decision to do the testing without FDA monitoring was motivated by a desire to help herpes sufferers without unnecessary delay.

Thiel’s rep “said, ‘We want to help people too, but we want to help a billion people, and we need to go through the FDA,’ ” Fernandez recalled.

The PayPal co-founder Thiel and a group of other investors committed $7 million to Rational Vaccines on Aug. 23, with the condition that future testing of the vaccine comply with FDA standards. . .

Good for them. I’d be leery of backing these folks, but Thiel won’t miss $7 million, and I’m sure he funds a number of long shots. A herpes vaccine would indeed be a good thing, but it’s not going to be easy to realize, especially by means like these. Overall, it looks like Thiel’s group is actually trying to yank these folks back to something like reality. I hope they realize what they’re getting into. It sounds like a good deal of the work done so far on this vaccine is not going to enhance the regulatory package very much. It may well be that when you actually do a reasonable, controlled trial of the stuff that it doesn’t do much good at all, but there’s no way of knowing that until you, y’know, do such a trial. Which is how things should have been done in the first place. All of Halford’s vaccine-cowboy stuff, instead of speeding things up, has only slowed the process down.

12 comments on “Not How You Speed the Process Up, Exactly”

  1. Isidore says:

    This is the kind of story that horror movies are made from.

  2. Kevin H says:

    So…sign off on doing an ethically-questionable trial that deliberately avoids FDA oversight, get $7 million.

    That’s not actually a good outcome, even if Thiel and co-investors expressed distaste. That’s a multi-million-dollar reward for “vaccine-cowboy stuff” that “has only slowed the process down”.

    This approach was a failure only if the goal was to get a safe vaccine tested and approved as quickly as possible. If one’s goal is to get venture capital as quickly as possible, this sort of shortcut seems to be an effective strategy.

  3. Matt says:

    It’s work like this that probably leads to additional fuel for the anti-vaccine fire. I say probably to soften the blow. The last thing we need is another round of vaccine fear mongering, but this guy evading the proper channels doesn’t help.

  4. Peter S. Shenkin says:

    Since the poor guy knew he was dying, he wanted to shoot a last bullet into the dark in the hope that it might possibly hit the target; in which case others would follow up. I doubt he was under the illusion that he had proven its value. If it does turn out to be valuable, more power to his memory. If not, well, it’s in the same boat with most drug candidates. If it turns out to be significantly harmful, that would seem to be the time to yell.

    1. Billy says:

      While I want to be as compassionate toward someone afflicted with a terminal illness, I don’t think the time to yell is after something bad happens. At least not in this case where this guy is intentionally ducking oversight. Sales of snake oil still exist in infomercials, but it’s still not the right thing to do.

      1. tangent says:

        Yeah, I think you get to yell at somebody negligently shooting a gun around, even if they happen not to hit anyone.

  5. Richard Kramss says:

    I constantly hear people complaining about the numerous regulations and “stupid rules” that the FDA enforces, and how it hampers development of new therapies for unmet medical needs. This is a grievous example demonstrating why so many of them are needed. As I learned from my graduate Regulatory coursework, the creative deceit exercised by these kinds of charlatans knows no boundaries. Besides slowing down progress of medical research, it will most likely invite the drafting of some new guidances.
    In essence, the FDA oversight simply ensures that clinical research is held to the same (or higher) standards of conducting “good science”.

  6. Crocodile Chuck says:

    I seem to recall an Alex Tabarrok post @ Marginal Revolution on Halford’s ‘work’.

    Like it was a good thing:

    “In another story, Lawrence Reed has the inspiring story of Bill Halford who has developed a not-yet-approved vaccine for Herpes. Herpes can be incredibly painful and it infects over one million people a year but the route to a vaccine has not been easy:

    Impatient with Washington, Halford injected himself, his family and a group of ten herpes patients. None of his family exhibited any ill effects, evidence that the vaccines were safe. All the sufferers enjoyed dramatic pain relief, suggesting effectiveness. The early success of his research led him to co-found, along with film-maker and entrepreneur Agustin Fernandez, a company known as Rational Vaccines, Inc. (RVx)). Its mission is to fight the herpes epidemic worldwide, using the live, attenuated strains that Halford created.

    Peter Thiel is a lead investor in Rational Vaccines. Sadly, Bill Halford contracted cancer and died this year at just age 48. I hope his company will carry the ball over the goal line”. [SNIP]

  7. Dr. Z says:

    Breaking Bad 🙂

  8. milkshaken says:

    I had seen enough over my years as medicinal and process chemist – and I would not take part 1) in early clinical trials (Ia/b, II) for cancer and 2) in clinical trials from a small startup biotech, especially from a virtual biotech that does no research in house

    These trials tend to benefit the investors in the shortest possible time with the least possible expense. Especially if I was dying and had just few months left – I would prefer not to be exploited, and tried to avoid a more dangerous and less effective treatment

  9. Roxbury says:

    Unconventional, risky, and a PR setback – – – yes. All the ingredients for a rouge scientist movie, sure. The press loves this stuff.

    The reporter who broke this story for Kaiser wrote of one or two people with adverse reactions. Is this unusual in a trial? Not really. But, it was the protocol that skirted the FDA that made it seemed as if this rouge.

    Like the trial, his research in preparing the article was probably not as thorough as it should have been. However, if one was to Google Rational Vaccines, there are a number of very favorable articles that resulted from the trial along with a video of a participant who claimed that he “got his life back.”

    A more balanced view just might be that Halford has something using a live attenuated virus for his vaccine. And, once vetted by a CRO, it just might be a game changer that will improve millions of lives and may be worth billions.

    Let’s not throw the baby out with the bath water and look at this pragmatically.

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