I think this was all but inevitable….
I think this was all but inevitable….
The Golden State Killer cold case begin cracked via information submitted to an online genealogy DNA database opens up a new dialog on privacy, DNA, and sharing….
As 20 Americans and Brits flew to a Caribbean island for a controversial herpes vaccine trial, many of them knew there were risks.
The lead U.S. researcher, William Halford, openly acknowledged he was flouting Food and Drug Administration regulations in the consent forms they signed. He would be injecting them with a live, though weakened, herpes virus without U.S. safety oversight.
Still, many of them felt upbeat when they arrived on St. Kitts and Nevis in the spring of 2016. They had struggled for years with debilitating, painful herpes. Halford, the creator of the vaccine, sounded confident.
Maybe they could be cured.
“It felt like paradise,” one of the participants recalled. “Or therapy combined with vacation.”
A year later, their optimism has turned to uncertainty. Memories of kicking back in a Caribbean hotel during the trial have been overshadowed by the dread of side effects and renewed outbreaks.
But they can’t turn to Halford, a Southern Illinois University professor. He died of cancer in June.
They also can’t rely on his university, which shares in the vaccine’s patent but says it was unaware of the trial until after it was over. Because the FDA didn’t monitor the research, it can’t provide guidance. Indeed, there is little independent information about what was in the vaccine or even where it was manufactured, since Halford created it himself.
At a time when the Trump administration is pushing to speed drug development, the saga of the St. Kitts trial underscores the troubling risks of ambitious researchers making their own rules without conventional oversight.
“This is exactly the problem with the way the trial was conducted,” said Jonathan Zenilman, an expert on sexually transmitted diseases at Johns Hopkins Bayview Medical Center in Baltimore. “These people are supposed to have rights as human subjects, but now there’s nowhere for them to go. We may never know if this vaccine worked, didn’t work or, even worse, harmed anyone.”
Rational Vaccines, the U.S. company co-founded by Halford, still hopes to market the vaccine. It touted success online and to other researchers, prompting millions of dollars of recent investment, including from a company run by President Donald Trump backer Peter Thiel.
Thiel, a PayPal co-founder who has excoriated the FDA as too bureaucratic, declined to answer questions about his investment, which occurred after the trial had ended.
Kaiser Health News interviewed five of the 20 participants in the clinical trial and several associates of Halford.
The participants agreed to speak on condition of anonymity because they don’t want to be known as having herpes. Most also said they feared retaliation from Halford’s company but hoped by speaking out some of their concerns might be addressed.
Their accounts, along with documents, a video and emails obtained by KHN from the offshore trial, pointed to what experts said were serious irregularities:
Halford did not rely on an institutional review board, or an “IRB,” which monitors the safety of research trials.
The company has said it doesn’t know where Halford manufactured the vaccine, so it isn’t known whether he followed U.S. government guidelines when transporting it.
Halford offered booster shots of the unapproved vaccine inside the U.S. FDA regulations prohibit such injections.
“The FDA goes after these types of violations,” said Holly Fernandez Lynch, a lawyer and assistant professor who specializes in medical ethics at the University of Pennsylvania’s Perelman School of Medicine. “[Researchers] can be prosecuted.”
SIU, however, did little to discourage Halford. The university, which has a financial interest in the patent, said it learned of “the concerns” only after his death. In August, after KHN asked about the trial, the medical school’s IRB launched an investigation into whether Halford violated U.S. regulations or university rules.
In a statement to KHN, Rational Vaccines acknowledged that Halford “discussed a myriad of concerns … including the potential need for booster shots.”
“Unfortunately, Dr. Halford is no longer with us to address all the ways in which he may have investigated his concerns …,” stated the company. It added, “We nevertheless wholeheartedly intend to continue his line of investigation in a clinical setting to international good clinical practice standards.”
Racing Against Time
Halford first broke with scientific protocols in 2011, shortly after he was diagnosed with nasal cancer and treated with chemotherapy and radiation, according to an account he later posted on his blog.
By then, Halford was in his 40s and had worked almost a decade at SIU’s School of Medicine.
Halford, who did not have herpes, realized his cancer might not give him much time. If he submitted to the FDA’s oversight, it would take years, he reasoned in his account.
He decided to become his own research subject, injecting himself more than two dozen times with the vaccine.
“There is an ongoing herpes pandemic that demands the scientific community’s attention today, not tomorrow,” he wrote in his blog, which by his count received thousands of hits.
The experiments on himself, Halford believed, demonstrated the vaccine was safe.
In 2015, Halford set his sights on launching an offshore clinical trial.
However, his unorthodox approach made some of his peers recoil.
“He sat in my kitchen and tried to convince me to join him,” said Terri Warren, a nurse practitioner in Oregon who was approached by Halford in 2016 to help with the trial. “He believed so firmly in his vaccine. He said, ‘Think of all of the herpes patients who are suffering.’”
Warren had previously worked with Halford on a different, IRB-approved trial studying a new blood test to diagnose herpes. This time, she said, she became concerned about his methods, including how he was selecting his participants.
“I told him absolutely not,” she recalled. “I didn’t want anything to do with it. I felt bad for him because he was dying, but I thought he had lost perspective.”
But Halford did find backers, including Hollywood filmmaker Agustín Fernández III, whose credits include action films and an award-winning documentary.
Fernández recently declined to respond to questions. But in an earlier interview this year with KHN, he said he initially contacted Halford to try to help someone he knew who was battling the disease. He said he didn’t have herpes, or a background in science.
Fernández, however, became such a believer in Halford, he said, he allowed Halford to inject him with the vaccine. In 2015, he co-founded Rational Vaccines with Halford and invested his own money into the company. That same year, the company licensed two patents related to the vaccine from the university.
“I felt like Bill had the answer, and we had to make sure he got a chance to prove it,” Fernández said.
‘Finally … Someone Who Cared’
As soon as news began spreading in the tight-knit herpes online community that Halford may have a cure, he began hearing from the most desperate who asked to be included in any future research.
For many, herpes is a mild disease that can be controlled by antiviral medicines. However, for some, it becomes a life-altering disease that destroys any hope of intimate relationships.
To several of the participants, Halford was an empathetic scientist who refused to give up on finding a cure.
“After dealing with doctors who had no answers, it felt like you were finally talking to someone who cared and could help,” said a participant in his 30s from the South who had described the trial as “paradise.”
There were other perks as well.
Rational Vaccines told some participants they would be reimbursed for their flight and hotel expenses. If they got through the entire trial, they would be given an extra $500.
As Halford organized two groups of 10 participants, he instructed them on drawing their own blood for the trial, according to a video filmed in a medical lab.
He proceeded with the trial from April to August 2016, giving participants three shots over three months.
Once in St. Kitts, many of them quickly bonded with one another and Halford. Even though they ranged in age from their 20s to 40s and came from different regions, they had the disease in common. They commiserated about how herpes had wreaked havoc on their lives.
“It was a relief to meet people who understood what we were talking about,” the Southerner said.
But other participants now say they noticed some troubling signs.
They received the injection in a house in St. Kitts, not a medical clinic.
Halford, whose gaunt frame made his cancer apparent by then, at times appeared disoriented.
Fernández, a constant presence, was introduced to them by name and made some of them uncomfortable when they socialized over drinks and dinner.
Some patients became anxious about their participation soon after receiving the vaccine.
One, a web developer in his 20s, felt ill after receiving just one dose.
“I experienced tiredness and ringing in my ears,” said the web developer, who reported the feelings along with “disequilibrium and slurred speech” continue to this day.
He said he decided not to return to St. Kitts for follow-up shots after Halford dismissed his symptoms as arising from a common cold.
Another participant, a Colorado woman in her 40s, said she told Halford she experienced flu-like aches and pains and tingling and numbness soon after the second shot. The symptoms were followed by an “excruciating” 30-day outbreak of herpes.
“I have new symptoms every day,” that woman later wrote Halford in an email exchange provided to KHN. “This is terrifying.”
Halford initially dismissed her symptoms, speculating they were caused by a mosquito-borne virus, she said.
She returned for the third shot but had her doubts. Halford and Fernández met her at a café to talk about her concerns, she recalled.
“[Fernández] kept saying, ‘You signed the consent form. You knew the risks,’” said the Colorado woman, who said Halford then removed her from the trial.
Another participant, a Californian in his 30s, said he went through with all three shots despite feeling a “terrible pain in my stomach.”
Halford then told him he had noticed in his research of mice that another version of the virus entered the gut of the mice and killed them, the participant said.
“I then thought maybe this is dangerous,” said the Californian, whose pain went away but his outbreaks did not.
Warren, the nurse practitioner in Oregon, said two participants tracked her down as a herpes expert. She said that they described possible side effects from the vaccine.
Halford had told participants he would follow up on their reactions to the vaccine for a year, according to the consent form. But he stopped sending questionnaires to the two participants who said they had been dropped from the trial.
Warren said that even when researchers stop administering a vaccine because of possible side effects, known as adverse events, they have a duty to track the subjects’ reactions.
“There is no doubt that these were adverse events that should have been reported,” Warren said.
Rational Vaccines did not respond to questions about the complaints. In previous public statements, it acknowledged that one of the 20 participants was concerned about possible side effects.
Some participants also wonder where Halford made the vaccine and how he transported it to St. Kitts.
Halford told his business partner he had made it outside of the United States, without disclosing where.
After the trial ended, some participants began complaining that the vaccine hadn’t worked. Halford and Fernández offered booster shots, according to four participants.
One participant, a man in his 40s who was also from California, declined to get the booster. He said he decided to go back to antiviral drugs when his outbreaks returned.
The Southerner said he agreed to allow Halford to give him booster shots at an office in Springfield, Ill., where Halford worked.
“It was between me and him,” said the participant. “He was doing me a favor.”
“I don’t know if it was a different strain or what, but he gave me a set of double boosters at the same time, one in each leg,” recalled the Southerner, who said he didn’t have records of the injections. He said he received them as Halford continued to collect data for the trial.
Months later, he said, he returned a second time for another set of boosters.
Courting Support Without Results
Halford, meanwhile, tried to persuade a U.S. scientific journal to publish a lengthy manuscript detailing the results of both his experiments on himself and his offshore trial. Halford put the cover letter on SIU letterhead.
In December 2016, only months after the trial had ended, Halford’s paper was rejected by the journal.
“This manuscript is partly a vision, partly science, and partly wishful thinking …,” said one reviewer for the journal. “Neither safety nor efficacy has been demonstrated by the data presented.”
Halford asked his former doctoral adviser, Daniel Carr, to attend a Rational Vaccines advisory board meeting. Carr, a University of Oklahoma Health Services Center professor, said he and other invitees heard glowing reports about the trial.
Carr agreed in May to present the trial data at a conference of herpes experts in Colorado.
A published summary of the event listed Carr as a lead author, though he said he wasn’t involved in the research.
“I just did it to help him out,” said Carr, who asked for his university’s permission to be on Rational Vaccines’ advisory board and is waiting for word on federal funding to study another version of Halford’s vaccine. “I also presented it because I thought that the scientific community would find it interesting.”
Despite its patent agreement reached in 2015, SIU said it was in the dark about Halford’s offshore activities until October 2016 — months after the trial had ended.
Halford, meanwhile, promoted his work at events attended by university officials.
In October 2016, Halford was a keynote speaker at an SIU-sponsored technology and innovation event to discuss his vaccine work.
Then, in April 2017, Halford and Rational Vaccines held a press conference to trumpet an investment pledge by Thiel’s company, according to materials handed out at the event. University officials, including SIU’s medical school dean, were invited speakers.
The university’s IRB is continuing its investigation, which includes scrutinizing whether Halford used university resources.
“If there are areas of concern, SIU will report those findings promptly to Department of Health and Human Services,” said SIU spokeswoman Karen Carlson. “We will also communicate our findings with the scientific community and the public.”
FDA spokeswoman Lauren Smith Dyer declined to comment on the trial except to say the FDA does not have jurisdiction over offshore trials that don’t seek agency approval.
Dyer, however, added that the export from the United States of an unapproved vaccine for research use and the injection of it on U.S. soil would be within the agency’s jurisdiction.
Even so, some participants don’t regret taking part in the trial.
“When you feel like a disease has ruined your life, you become desperate,” said the Southerner, who believes the boosters have lessened his outbreaks. “Some people contemplate suicide. You’re willing to do almost anything.”
Other participants still hope for some sort of accountability.
“I feel like without a doubt that my symptoms were vaccine-related,” said the Colorado woman. “I feel like it triggered something that I’ll have for the rest of my life.”
No matter what, experts said, the university has a responsibility to conduct an in-depth investigation. So far, the university has not reached out to participants who spoke to KHN.
“This researcher went rogue,” said Fernandez Lynch, the lawyer who specializes in medical ethics. “It’s true that universities can’t stand behind their researchers watching their every move. But when one of their own goes rogue, a university should launch an aggressive investigation, interview the participants and make sure it never happens again.”
I’m so tired of #Homeopathabullshit….
As all of the discussion on Healthcare reform comes to a head, I think it warrants some comments from me regarding “The Greed of Pharma”. Let me start by saying that Pharma is a for-profit business like any other.
I think it is important to note that neither pharma (nor the insurance industry for that matter) has particularly high profitability (ROE %’s). The following industries have a higher ROE % (Return on Equity rating) than Pharma (21 of them, and in the order listed). Cigarettes has nearly triple Pharma’s profitibility (and the US Gov is a de facto share holder); Aerospace has double. So why would Pharma be expected to foot the healthcare bill (and squeal like a pig -to paraphrase Congressman Marion Berry of Arkansas) when there are so many other more deserving candidates?
Aerospace/Defense – Major Diversified
Information & Delivery Services
Diversified Computer Systems
Beverages – Wineries & Distillers
Processed & Packaged Goods
Auto Parts Stores
Education & Training Services
Industrial Metals & Minerals
And this dear readers, is why we test our software….
From left: D.C. Councilman Jim Graham, Metro General Manager John Catoe, NTSB board member Deborah Hersman, Tri-State Oversight Committee Chairman Eric Madison and Federal Transit Administrator Peter Rogoff are sworn in before a House panel. (Examiner)
Metro’s alert system continues to fail periodically in the area of track where one Metro train crashed into another last month, killing nine and injuring more than 70 people.
A component of the automatic train alerting system that may have failed to prevent one train from knowing another was stopped ahead on the track continues to flicker intermittently in that same spot even when new equipment is used, National Transportation Safety Board member Debbie Hersman testified Tuesday. The device removed just five days before the crash as part of routine maintenance doesn’t fix the problem, either.
The revelations were part of a three-and-half hour congressional oversight hearing in which officials testified about the deadly June 22 crash and the transit system’s overall funding shortages and lack of regulation.
The continuing problem at the crash site is why Red Line riders are still experiencing delays along the line more than three weeks after the crash.
Inexplicable failures of software happen.
As a QA professional I scrutinize the systems, processes, and results (data) of my client groups (the operational areas….i.e., the people who do the real work). This can be very frustrating for people; especially those who work hard, do good work, and aren’t used to having someone doubt them or subject them to the third degree….physicians often have a particularly difficult time with this.
I understand this and strive to make my intrusion on their daily work as unobtrusive as possible. I also try to explain to them exactly what my thought processes are and the rationale for my questions. One of the things I like to tell my client groups/auditees is that I am an optimist who’s paid to be a pessimist. That’s simple and to the point and it seems to convey my position to my client groups/auditees rather well.
More accurately, I’m an optimist who’s paid to be the exact right combination of the guy who sees the glass half full, the glass half empty, and the cracks in the glass. They pay me to see the good, the bad, and the ugly; to take a good system and try and break it…..just to see if someone can.
Below, I’ve assembled a few (real) scenarios that I think illustrate my role:
1) In this case, I was auditing at a Clinical Investigators site (a doctor’s office). At one point in our exit interview he felt that I (a non-physician) was questioning his medical opinion. To which I told him, “I would never question your medical opionion; I’m not qualified…..but based on your source notes, I can’t tell what your medical opinion was….or even that you had one”. Understanding stole across his face…..Documentation. That’s what was missing. He was doing the work in a stellar fashion, but not documenting it sufficiently.
2) Another physician was less convinced of the need to explicitly document his diagnosis. “Any clinician would immediately have the same diagnosis…its self-evident!”. Again as a non-physician, I told him that I was sure he was right, but that FDA would likely send a “non-clinician”; someone who would look at his documentation in a manner more akin to that of an attorney than of a medical professional….”Oh, I think I understand what you’re telling me now.”
3) A third physician tried to correct me on calling study participants “subjects” rather than “patients”….”subject sounds so cold and uninvolved”. To this, I explained my position that a “patient” is someone who comes to a doctor looking for something tried and true to make them better. A study “subject” is someone who is taking a gamble out of philanthropy, desperation, or a combination of both….someone that, with their informed consent, we are putting in some measure in harms way. They deserve our highest respect and greatest level of care. Patients are very important; study Subjects are doubly so. This doctor seemed a little irritated at my little philosophical tirade (short though it was), but he seemed to understand the point I was making…I guess he thought I was an idealist of some sort…
4) While meeting with a team that was conducting validation testing on a clinical computer system, some on the team were frustrated by the level of testing that I was recommending (requiring?). “Well in an ideal world, we would test everything…..”….I had to correct him, “In an ideal world, software testing wouldn’t be necessary because everything would work right out of the box in a perfect and unqualified way…We test our software to ensure that it is actually working like we think it is”. He didn’t like that response, but at least he was quiet”.
Are there any others with anecdotes or questions relating to GxP?
I was reading some blog posts over at Wellsphere when I saw the following thoughts on the placebo effect from Seth Roberts
1. Getting better for the wrong reason.
2. Wasting a lot of money.
It sounds like a joke — #1 isn’t even harmful, whereas the cost of health care is a very serious problem. Yet the FDA and legislators with FDA oversight have been given this choice — and chosen #1. They have chosen to protect us against #1 but not #2.
If you get better from a placebo effect, that’s the wrong reason. How dare you! The requirement that drugs be better than placebo controls prevents this from happening. The requirement might have been — but isn’t — that a new drug be better than pre-existing alternatives. Many aren’t but they are always more expensive — not to mention more risky.
Now Seth has a Ph.D. in psychology, blogs on science-related topics, and seems like a smart enough guy, but his post is a bit misguided.
1) The reason that drugs are required to perform better than a placebo is because the placebo effect tends to only occur in a small set of patients. That is that the mental makeup of a specific patient is the cause of a placebo response (irregardless of the treatment). It is also not clear whether a placebo respondee is “actually getting better”. It is just as likely that they were not actually sick in the first place (or as sick as they thought).
2) Those patients who are not predisposed toward exhibiting placebo responses need to be given an actual effective treatment to “get better” and therefore deserve medications that exhibit “better than placebo” characteristics. Giving such a sick patient a sham treatment (rather than one that can actually work) can be very harmful in that the person’s condition can actually worsen.
3) There is a requirement from FDA (and regulatory agencies worldwide) that new drugs be as good or better than existing medications; or that they provide some sort of unique benefit (or reduced risk).
4) The expense of new medications is largely due to the high cost of research to make those medications (and fund future research). The low-hanging fruit is largely gone.
Welcome to my Blog. I’ve had this domain (www.tjkuhn.com) for many years now, but it has mostly served as just a placeholder for “something” in the future. Not long ago, I became excited about blogging after listening to a book-on-tape of Robert Scoble and Shel Israel’s book on the subject, Naked Conversations. Since then, I’ve been reading blogs and planning my own contributions, but have been struggling as to how to start. I’ve come to the conclusion that it really doesn’t matter how I start, just that I do. So here I go, midstream and mid-thought.
I’m a Quality Assurance professional working in the Pharmaceutical sector. In that role, I see a lot of things. The point of this blog is to share some of that. Additionally, I’m hoping that through the related ongoing dialog on the blogosphere that I will be able to learn new things, broaden my perspective, and refine my own positions.
We will see how my blog develops, but for now, I’m planning on covering a wide range of compliance, bioethics, and technology issues. My initial target audience will be professionals working in (or in conjunction with) the Pharma industry. I’ll be looking at things from the GxP perspective. That being said, I can easily envision posting information that may be interesting or useful to consumers who are interested in the health care system; its past, present, & future; and why it works like it does. We will have to see.
Now it is time for disclaimers. I have a favorite that I’ve seen around the web (though I can’t seem to find it now):
The views expressed within are opinions. They are not necessarily those of my employer, not necessarily mine, and probably not necessary.
Let me explain:
1) Nothing on this site, neither explicit nor implied, should be construed as an official or unofficial position of my employers (past, present, or future).
2) Some of the items I post will be borrowed ideas. If I know where something comes from, I will attribute it. Please let me know if you know of the source of an idea that I haven’t and I’ll gladly add appropriate references.
3) My posts will include items with various degrees of polish. Some of them I’ve been thinking about and developing for decade(s)….and some of them I thought of ten minutes ago. My thoughts will likely change over time. Please challenge me if you feel my position on any topic is misguided. That is part of the point of this blog and I will be very thankful for the input.
4) I serve as an advisor to my clients on compliance issues. If I work with you (and doubly so, if I do not), opinions that I express here are just that….opinions. Do not construe anything I write here as definitive, official, well-researched, or prescriptive. If you want something official, please contact me directly.
With that, let’s get on with the dialog.
~T. J. Kuhn