The Theranos contretemps as a serious scandal

Last Thursday WSJ released a long article on Theranos clinical lab. In this blog you may check my February and July posts on this firm under the title: A closely guarded secret. As you may imagine, such a title was not coincidental. There were some clues that justified it, something unusual was happening. And WSJ has contributed to shed light on the issue. All the details in it. Basically, the summary is that analytic validity and clinical validity is under compromise. This is an exemple:



If you want to read a first person account, you'll find it here and here. Some additional articles: Wired, New Yorker, Clinical Chemistry and Laboratory Medicine (CCLM), Forbes, NYT, WP,...
This is not only a contretemps, it is a serious scandal and a huge problem to credibility for this start-up.
From Wired:

Theranos got a lot of traction by tapping into the frustration—both from consumers and the medical community—that diagnostic testing is too painful, too slow, and too expensive. “Their problem is they tried to do it with existing diagnostic instrumentation, instead of innovating new diagnostic instrumentation,”

Theranos is a black box that has touted results rather than process. “The ability of the lab medicine community to police and correct itself depends on that flow of information,” says Master. Instead, Theranos’ research was internal, and rather than submit their work to peer review the company cited their FDA approvals as evidence that the technology worked.

At least in the USA there is a regulator, the FDA, lab regulation in Europe was enacted in 1998, completely outdated under a third party scheme, not a direct public regulator. Therefore, there is a pressing motive to speed up new and different rules in Europe. Microfluidics and nanotechnologies are calling for and urgent overhaul.


 PS. An statement from WSJ:

In 2005, Ms. Holmes hired Ian Gibbons, a British biochemist who had researched systems to handle and process tiny quantities of fluids. His collaboration with other Theranos scientists produced 23 patents, according to records filed with the U.S. Patent and Trademark Office. Ms. Holmes is listed as a co-inventor on 19 of the patents.

The patents show how Ms. Holmes’s original idea morphed into the company’s business model. But progress was slow. Dr. Gibbons “told me nothing was working,” says his widow, Rochelle. In May 2013, Dr. Gibbons committed suicide. Theranos’s Ms. King says the scientist “was frequently absent from work in the last years of his life, due to health and other problems.” Theranos disputes the claim that its technology was failing.

The Theranos scam whistleblower

 Thicker Than Water

From the hero whistleblower of the infamous Theranos scam, Thicker than Water is a look at never-before-revealed details behind closed doors at the company, revealing a cautionary tale of corporate bullying, gaslighting, ego, and wealth run amok in Silicon Valley.

Tyler Shultz had been in the workforce for less than a year when he emailed Elizabeth Holmes, his employer and the CEO and founder of Theranos, with concerns that the company’s lab practices were faulty, ignored quality control, and were potentially dangerous to patients. The COO fired back with a dismissive and insulting email, to which Tyler replied: "Consider this my two weeks’ notice."

From there, his life spun out of control at the hand of Elizabeth, her team of high-powered lawyers, and the patriarch of Tyler’s own family, George Shultz—one of America’s most prominent statesmen, who sat among the top of the Theranos Board of Directors. And yet, Tyler forged on. To protect his own conscience, the honor and reputation of his grandfather, and the health of patients worldwide.

Thicker than Water is Tyler’s as-told-to story—a harrowing and heartbreaking roller coaster of biomedical drama, family intrigue, and redemption—that will ultimately make you feel as though you are at a dinner party, seated next to a brilliant friend with one hell of a story. 

Fake lab tests

Bad blood

We all know that we live in a post-truth society. But this may have strong effect in your health. The case of Theranos, a US lab is explained in an excellent book by John Carreryrou is a precise example. You create an expectation that with a blood drop all tests can be done, you develop the narrative, the social and entrepreneurial support, and...while the regulator is on vacation (as usual) you perform fake test that can endanger your health. Imagine that your coefficient of variation is 34-48%, while it should be less than 10%!. The results may hurt you directly.
The book provides a lot of details:

As for the lab itself, it was a mess: the company had allowed unqualified personnel to handle patient samples, it had stored blood at the wrong temperatures, it had let reagents expire, and it had failed to inform patients of flawed test results, among many other lapses

And strong messages for start-up investors:

By positioning Theranos as a tech company in the heart of the Valley, Holmes channeled this fake-it-until-you-make-it culture, and she went to extreme lengths to hide the fakery. Many companies in Silicon Valley make their employees sign nondisclosure agreements, but at Theranos the obsession with secrecy reached a whole different level.

FT recommends this book for this summer, and I agree that it will help you to understand and avoid similar fake business that we can detect around us. It should never happen again.

The media and the Theranos incredible deception

On Theranos failure, highly recommended for journalists.
From CBSNEWS, a basic piece to understand the power of the media in creating and destroying (false) value:

Was the media duped by Elizabeth Holmes?
A conversation with 60 Minutes about media coverage of the rise and fall of Elizabeth Holmes and her hot startup, Theranos

A closely guarded secret (2)

Direct Access Testing is the next battle for a new market for lab testing. This is at least what Theranos considers and has been lobbying for. Last December in The New Yorker there was an explanation about the firm and its goals. Afterwards JAMA added some caveats on the secretive way of conducting business and I wrote a post on that. Now The Economist has published an article with the details of the current situation about their business model.
Selling tests directly to the patient is a controversial issue. As in most of prescriptions, patients don't know enough to prescribe for themselves. However, how much is enough?. Arizona is starting to liberalise such prescriptions after Theranos successful lobbying efforts. Professional societies reflect in a position paper their perspectives on the issue.
My view is very straightforward: avoiding commercialism in health care. Under insurance coverage, prescriptions should be required after being cleared by regulators. Without insurance coverage, recreational tests have also to be licensed by regulatory authorities under a disclosure process that has not been the Theranos case. Nowadays, it still remains a secret. Selected tests could be accepted without prescription according to its implications on Health and information accuracy.

The Theranos contretemps as a serious scandal (2)

The DropoutPodcast by ABC Radio & ABC News Nightline

The inventor

Now you can hear the ABC radio podcast in 6 chapters on Theranos scandal. Report at The Verge. Highly recommended.

And the HBO new documentary explains all the details in 2 hours. The trailer:

Theranos on trial

 Podcast: 'The Dropout: Elizabeth Holmes on Trial'

ABC News' #1 podcast is back with new episodes, available on Tuesdays.

Money. Romance. Tragedy. Deception. The story of Elizabeth Holmes and Theranos is an unbelievable tale of ambition and fame gone terribly wrong.

You'll find it in Spotify every week

 

Theranos: a massive fraud and epic failure

The Theranos deception on CBS News 60 Minutes

A quantum leap on microfluidics for in vitro diagnostics

 On the Wireless Microwave Sensing of Bacterial Membrane Potential in Microfluidic-Actuated Platforms

You may remember my posts on Theranos, the company that wanted to solve in vitro diagnostics (IVD) with a drop of blood. The underlying technology was microfluidics, however at that stage was inmature, and finally Theranos was a massive fraud and Elizabeth Holmes is right now on trial.

Now you can read an interesting article in Sensors journal that tries to combine microfluidics and wireless technologies for detecting bacteria. Microfluidics is defined as the manipulation of a fluid in micrometer-sized structures or channels. In such microchannels, the behavior of a liquid is significantly different than at the macroscale. Surface effects and viscosity start to dominate and flows such as laminar flows are more predictable.

If this procedure finally works in practice, it would represent a quantum leap on In Vitro Diagnostics. Time will tell us if this is so.

Els venedors de fum i la regulació de pa-sucat-amb-oli

 En Joan Font de Comediants va decidir celebrar els 50 anys del grup fent una obra amb el títol "El venedor de fum", una història personal reflectint tot el que ha estat la trajectòria. És evident que en Joan Font és un venedor d'històries magnífiques que ens han omplert moltes hores de joia i distracció. Unes històries on l'audiència gaudia d'allò més bé. I si hagués de triar una obra de les moltes que van fer, jo diria "El llibre de les bèsties", l'obra magna de Ramon Llull posada en escena muda. Impressionant. Voldria tornar a veure-la.

Doncs bé, de venedors de fum amb altres consequències més preocupants en tenim molts. Ahir entrava a la presó per 11 anys Elizabeth Holmes pel cas Theranos, un gran frau diagnòstic basat a Silicon Valley. N'hem parlat molt aquí. Però hi ha altres venedors de fum que sota una aureola de certesa,  seguretat i eficàcia, ofereixen una profunda incertesa que sovint no acaba qualificada pels tribunals com a frau. Això succeeix quan el regulador no ha fet bé la seva feina (i els tribunals tampoc) i ja ho vaig explicar pel cas dels diagnòstics in vitro fa 6 anys. Doncs bé ara que ja és efectiva la regulació ja podem veure el desgavell que es produeix. En temps de pandèmia es va fer evident. Resulta que de les noves proves per detecció de Sars-COV-2 no en sabíem a Europa la sensibilitat i especificitat, arribaven amb una marca CE que fan uns organismes i que no serveix per saber la magnitud dels falsos positius i negatius. La solució era esperar que la FDA digués quina era la sensibilitat i especificitat d'una prova per tal de comprar-la. Tot això, en general, la gent del carrer ho desconeixia i ho desconeix, només intuïa que hi havia resultats que no eren certs i que si els feien dues vegades no sortia el mateix.

Ara que ja ha passat la pandèmia, tenim el mateix problema però agreujat. Les empreses han après que la regulació de pa sucat amb oli europea és una oportunitat a explotar. I dic això perquè veig una febre de comercialització de noves proves diagnòstiques sense cap avaluació independent i que quan hi ha una dada de sensibilitat i especificitat resulta que només és publicada principalment pels empleats o accionistes de l'empresa que les fabrica. I ara volen que els mateixos que han subvencionat la recerca siguin els seus clients. I ja hem tancat el cercle. I si voleu hi podem afegir la caixa negra de les patents i ja ho tenim tot. Just avui que hi ha tres països que passen de llarg de la nova regulació europea de patents, sabeu quins són? Democràcies plenes i modernes: Polònia, Croàcia i Espanya. I si voleu podem afegir que han patentat privadament les proves diagnòstiques quan han disposat de finançament públic. I aquí m'aturo. L'últim que tanqui el llum i la porta.

'Pseudomnesia

Theranos scandal in the valley of hype

 

European health regulation on lab tests, the final round? (2)

Last week, Theranos clinical lab has received more bad news. Though the final resolution is still pending, all available informations raise concerns about the acuracy of such lab.Could this happen in Europe? My feeling is that the outdated and obsolete regulation could replicate the story.
In Europe, in vitro diagnostics regulation was decided 18 years ago!. The last proposal debated two years ago in the Parliament got no final agreement. I have explained the inefficiency of european parliament formerly. Health care safety and quality deserves better regulation and specially in lab tests.
Beyond safety issues, the value of lab tests require deeper assessment. Current proposals are not taking into account properly this issue. Now is the moment to introduce it in the final proposal, otherwise it will forgotten for the next two decades.

PS. Have a look at this article: A Systematic Review of Health Economic Evaluations of Diagnostic Biomarkers

Manhattan i Queens (Fragment), oli sobre tela, 60 × 150cm

Next week Josep Segú starts its exhibition at Sala Parés

Theranos details explained: the "inventor" that fooled so many smart people

The Inventor: Out for Blood in Silicon Valley (2019)

Former posts have explained the story, now a 2h. HBO documentary adds details:

The uncertain cost of clinical trials

How much do clinical trials cost?

A research on seven top pharmaceutical companies has provided fresh data about costs of clinical trials:

For the trials in the data set, the median cost of conducting a study from protocol approval to final clinical trial report was US$3.4 million for phase I trials involving patients, $8.6 million for phase II trials and $21.4 million for phase III trials.

If you compare these data with the total drug costs (2.6 billion), you may ask yourself how all these costs are estimated. Maybe all this information is wrong and useless.

PS. Waiting for the new book on Theranos scandal

Pharma sales 2017

Kupka au Grand Palais

Les hores baixes de la indústria farmacèutica catalana

La nova queixalada a la teranyina: el cas Esteve

 Què cal fer quan les dades no ajuden a un bon titular? Doncs maquillar-les. Fa uns mesos va sortir en portada per exemple com Catalunya acumula el major nombre de plantes de producció farmacèutica, 79 de 173. El que no deien és la producció, i per tant que les fàbriques més grans i de les empreses capdavanteres no es troben aquí. 

Ara a Via Empresa podeu trobar un detall de què ha passat amb la indústria farmacèutica catalana, una davallada constant i paulatina. Una informació que no trobareu als mitjans de comunicació convencional, perquè no interessa. El missatge és clar, la pèrdua continuada de posicions en termes de propietat i de mercat. El motiu? Molts, però està clar que algú va decidir i està decidint fer caixa abans de fer els deures.

Marcelo Brodsky

PS. Elizabeth Holmes, Theranos, va entrar ahir a la presó per complir sentència de frau durant 11 anys.

L'assaig clínic mai vist per al cribratge del càncer

Li pregunto a Chat GPT sobre l'assaig clínic més gran en nombre de participants i em diu que és ASPREE, sobre l'aspirina i prevenció cardiovascular. I veig que Galleri, l'assaig clínic de GRAIL sobre cribratge de càncer al NHS hi ha 140.000 participants. I jo penso, això és molta gent i el Chat GPT4 no ho ha copsat. 

This is a trial in a large population in England to assess the performance and clinical utility of GRAIL’s multi-cancer early detection test when added to standard of care. Participants are randomized to either a test or control arm. The study teams remain blinded throughout the study. Participants who test positive will be referred for standard of care investigations and treatment in the National Health Service (NHS).

The study has enrolled approximately 140,000 people aged 50 to 77. Unless diagnosed with cancer, participants in both arms are asked to return for annual visits at approximately 12 and 24 months. All participants whether test positive, test negative or not tested will be followed for cancer and associated outcomes via linkage to NHS routine datasets.

Els detalls de l'assaig els trobareu aquí. I si voleu veure la validació, aquí. I mentrestant el regulador segueix pensant si autoritza la prova, resulta que ja es troba al mercat.

Health information, such as whether someone developed cancer and how it was treated, is collected from centrally held NHS records for up to 10 years after people’s first appointment. This allows the researchers to easily track people for whether they get cancer, even for people who may have moved home.

People who are diagnosed with cancer while they are taking part in the trial may not need to attend further trial appointments to give blood samples.

A quina data s'acaba l'assaig clínic no se sap del cert. Després de llegir tot això espero que se sàpiga quina és la sensibilitat i especificitat de la prova segons càncer detectat. Dic això perquè no he sabut veure com s'avaluen els falsos negatius, ni els falsos positius. I en un moment concret diuen que haurem d'esperar 10 anys. No ho sé, potser m'ha passat per alt.

Més detalls, aquí.

Mentrestant la Unió Europea ha prohibit la fusió Illumina-Grail, i ja veurem com acaba. Per ara els mesos passen i res de res...

Galleri, el test detecta (diuen) 50 tipus de càncer amb una gota de sang que cerca ADN circulant per 1.000€ (diuen, diuen).

Més d'un i més de dos volen saber si estem davant d'un nou cas Theranos, (jo vull pensar que no) i per això han començat aquest assaig clínic. A FT del dijous hi ha més detalls. I ho fan a UK perquè a Europa aquesta empresa hauria d'estar prohibida fins que no compleixi les resolucions de les autoritats.

The smart money in tech would not have made this mistake

It's about Theranos. You may find my previous posts in this link. Now SEC has confirmed that was a "massive fraud". That's it. If you want a good analysis check FT.
Microfluidics is not an easy prêt-à-porter technology. Many people knew it but Mrs Holmes has been selling it as snake-oil. And as usual in these cases, the end of the film is already written. She can't go to the lab for the next 10 years, a fine, and the company may be closed. All started with and article by Mathew Herper in WSJ. An innocent article with an innocent question that she couldn't answer. That's all. Silicon valley smart money would not have made this mistake.

Modigliani exhibition in Tate Gallery now

A closely guarded secret

Stealth Research. Is Biomedical Innovation Happening Outside the Peer-Reviewed Literature?

How can we identify a snake-oil seller?. Not so easy. Have a look  at JAMA, John Ioannidis article shows his concerns about Theranos, a company that is providing lab services with a new propietary technology that has no peer-review article in any scientific publication. Nobody can check tests sensibility and specifity, no external quality controls, and so on.
If this is the path for the future of health care provision, then I am really concerned because it will be a complete disaster. No consumer protection, no regulation, uncertain science and more uncertain outcomes. After all this years, is this what citizens deserve?.
Such style of "laissez-faire, laissez-passer" medicine could represent huge profits for some and a big loss for everyone.
Otherwise some alternative should be proposed to boost publication and transparency. The author's suggestion is the following one:

To solve this conundrum, it may be necessary to find ways to realign the reward system for innovation. One possibility is to make the scientific literature more receptive to innovators. This could include models in which reports of disruptive discoveries that are in dissonance with the mainstream can still be communicated as preprints without prior peer review, perhaps in the same way as the successful example of arXiv in the physical sciences, which has now reached 1 million e-print articles. That there has been no peer review of these initial reports should be transparent to researchers and the public.

Thus, some better regulatory process is needed so that innovative ideas for financially successful applications can be scrutinized by the wider scientific community as to their validity. A company should not be forced to disclose its science secrets in detail, especially while its efforts are still exploratory rial-and error and while creating basic elements for its products and services. However, if a product or service reaches the point at which it generates substantial revenue, the science behind it should then be communicated in detail to ensure adequate review.