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Dr. Lorna Speid  

We Need to Know – Death of a Healthy Volunteer



The news is just breaking that a clinical trial conducted in France, and involving healthy volunteers has resulted in several of them being seriously injured. One of them died over the weekend, after being pronounced brain dead shortly after being dosed. Naturally, we have to wait for the investigations to be conducted and the dust to settle to find out what, if anything, could have been done better.

We were here not too long ago for TeGenero’s debacle with TGN1412 (2006). Healthy volunteers were seriously injured during their participation in a first in man study. After an extensive series of investigations we identified the following, amongst other issues:

  • The healthy volunteers were not truly informed consented
  • The study was poorly designed
  • The CRO did not demonstrate an appropriate level of competence
  • The animal toxicology and efficacy studies that predicted issues in humans were not interpreted appropriately prior to research subject enrollment

The death of any research subject is tragic, but the death of a healthy volunteer is something that should not happen.  I have admiration for someone that would put his or her health on the line to further medical science.   No healthy volunteer expects to put their life on the line. We have to ensure that we are asking the right questions to find out what went wrong.

When something like this happens the tendency is to take cover and try to deflect blame as much as possible. It has been truly disappointing to see the French Health Authority representatives giving out as little information as possible. These tragedies are relatively few, but when they occur we need an open process so that everyone can learn the lessons that need to be learnt.

I understand that there is a need to gather all the information from the documentation systems, but when someone has been declared brain dead in a clinical trial, other participants in the clinical trial have a right to know so that they can determine if it is in their best interests to remain in the clinical trial. Other researchers conducting research on similar molecules need to review their data to determine if their patients are likewise at risk. To keep this information under wraps is inappropriate.

I recall when Jesse Gelsinger died during his participation in a gene therapy trial, the US FDA and Recombinant Advisory Committee very professionally conducted an open and transparent Advisory meeting, soon after his death. The result of the open and rapid review was that numerous failings that had taken place were uncovered. I daresay the same failings are still ongoing in similar institutions today, but at least others could learn from the mistakes of the team that conducted this study.

I extend my condolences to the research subject’s family, friends and colleagues. For his sake, we must find out what went wrong, and how the risk of this happening again can be significantly reduced.

Lorna Speid, Ph.D.

Lorna is the author of Clinical Trials: What Patients and Healthy Volunteers Need to Know. This book was published by Oxford University Press in 2010.  Anyone considering entering a clinical trial is recommended to ask for a copy from their local libraries, or to purchase a copy online or in major bookstores.

Did it have to take Ebola …?

The outbreak of Ebola is now receiving the attention that it needs. The death of Thomas Eric Duncan, the first Ebola patient to die from the disease on US soil is a wakeup call. The first Ebola patient to die from the disease in Europe (Spain) is likewise a wakeup call.

For months Ebola was regarded by governments around the world as an African disease.  The attention given to it has been abysmal as a result. Ebola certainly didn’t seem like a disease that would disrupt the lives of people in developed and comparatively wealthy countries. The rate of infection of Ebola is doubling in the affected African countries every 2 to 4 weeks. This now presents real danger to whole communities beyond the borders of Africa because of global air travel and speed with which a contagious disease could spread as a result. This would obviously have an impact on the global economy. Clearly real action must now be taken to contain the epidemic at its source.

How should patients be treated and managed who have the disease? The disease appears to require expert use of aseptic technique for all those involved with the treatment of patients in Africa and elsewhere. The problem is that very few people are truly trained in the use and application of aseptic technique. The Spanish nurse that contracted Ebola after nursing the patient in Spain, has now recalled that she touched her face with a soiled glove.  The truth of the matter is that even taking off the soiled suit presents real challenges, and is likely to result in the carer’s skin coming into contact with the soiled parts of the body-suit unless extreme precautions are taken. This means that patients must be treated in specially designed facilities like the one at the Royal Free Hospital, in London, United Kingdom, and Emory Hospital in Atlanta, USA, unless many other people including nurses and doctors treating them are to be infected.

What action can be taken to stem the crisis at its source? Western governments often want to throw money at the problems in the developing world. The interesting thing is that if one follows the trail of the money spent in developing countries, it most often ends up being spent back in the donor country, or benefiting the donor country in some way. Anyone that has watched the news about Ebola has seen the “hospitals” in Sierra Leone and the other parts of Africa devastated by Ebola. The primitive state of the facilities is a disgrace. How can anyone be surprised that Ebola has spread under these types of conditions? This begs the question, will the millions of USD now promised for the Ebola outbreak lead to the construction of specialist hospitals that are properly equipped to address these types of epidemics in the future? Will the infrastructure be put in place to address the many tropical and other diseases that these countries are ill equipped to address?  Will staff in these specially constructed hospitals be given the training that is needed to care for the patients with Ebola and other infectious diseases? Without the specialist training, this crisis is only going to get worse. How can we spend 600 million USD in the few weeks that are available without wasting the funds and leaving the countries in the same condition they are currently in healthcare-wise?  Certainly the building of basic and functional toilet facilities  and availability of clean water would help to ensure the most basic of hygiene standards are addressed for those who live in rural areas. Cultural and lifestyle issues that support the spread of the disease must also be addressed through education perhaps using properly designed social media campaigns.

We cannot look at needed solutions without looking at the regulatory system for assessment of new treatments. The experimental drug ZMapp produced by MAPP Pharmaceuticals (San Diego) has been made available to some of the patients who have Ebola in the US, Africa and Europe. Some of the patients who received the drug have recovered, and are alive today. The drug remains unlicensed for commercialization. One certainly hopes that the company is collecting as much information as possible about the conditions of compassionate use to support licensure. In the case of ZMapp, the US regulatory system allowed itself to be bypassed because of the crisis situation.  It will be interesting to see how the FDA and EMA will respond to this situation now that several other experimental treatments are in development for Ebola. Will the regulatory review system be suspended so that these treatments can be approved and made commercially available at profit for the companies that have developed them? The Animal Rule is in place to allow the commercialization of treatments tested in animals where it is unethical or too dangerous to test the treatments in patients.  Treatments like ZMapp may qualify under the Animal Rule for ethical reasons.  For example, African patients with Ebola may be induced to be dosed with an unlicensed experimental drug even though it is unlicensed, but is this ethical? These are interesting but important questions that need to be addressed.

It is tragic that it took Ebola for everyone to begin to look at the tragic state of affairs of healthcare delivery for millions of people in Africa.

Don’t Question the System or Else!

What do you do when your little boy is diagnosed with a brain tumor and you do not agree with the treatment proposed by physicians in an NHS (UK) Hospital? On 28 August 2014, one family took their little boy to another country to seek the treatment they considered in his best interest. What happened next stunned not only the parents, but the whole United Kingdom, and the world.  Not only was the little boy removed from their care, but the parents were thrown in jail in Spain where they had taken him. Some of you that have not been following this story may make the assumption that these must have been despicable parents.  Surely they must be parents who are neglectful, abusive and downright unworthy of the privilege of being parents. What was their crime?

Ashya King is the British little boy who was diagnosed with a brain tumor. He underwent surgery in a UK hospital to remove his tumor. The next step in the process was for him to be treated with radiation to the brain to destroy any remaining tumor cells. After detailed research and consideration, the parents came to the conclusion that they could not accept the treatment approach available under the NHS. They wanted Ashya to receive radiation using Proton Beam Therapy. This is a targeted and therefore less damaging way of irradiating the area where the tumor was located. It destroys less normal cells than the normal radiation treatment. Proton Beam Therapy is not available on the NHS. Although Ashya was assessed for this treatment to be paid for by the NHS, the parents were told that he was not a suitable candidate. The parents removed him from the hospital and took him to Spain where they own a villa. Their plan was to sell the villa and pay for his treatment abroad from the proceeds of this sale.

Like most literate, educated parents, able to think for themselves, they had conducted their own research, most likely on the internet. You can Google anything these days. On the basis of the damage that would have been caused to Ashya’s cognitive abilities, they removed him from the hospital.

Fortunately, the UK and worldwide press got a hold of the story, and the British public made their feelings clear. Soon, David Cameron, the UK Prime Minister was embroiled in the affair and asking for reason and sensitivity to prevail.

The parents are now out of prison. Their son is receiving Proton Beam Therapy. He is making reasonable progress. What lessons can be learnt about this situation?  It is clear that some physicians don’t like their decisions being questioned by those that they consider less medically qualified than they are. I think most of us knew that already. The physicians in this case felt that the parents were not qualified to make decisions about their own son’s care. In fact, the father, Mr King claims that they were told, that their son would be taken away from them, and they would not see him again until he was 16 years old if they continued to question his care.

If this is true and the physicians over-reached in this way, what confidence can be placed in the judgment of those involved in the refusal of Proton Beam Therapy on the basis of unsuitability when Ashya has been deemed to be suitable for this treatment? The NHS is now paying for this treatment in Prague. We wish Ashya and his family a smooth ride from this point on and applaud them for fighting a system which was not working for them or their son.

Some questions to ponder:

Where do you turn when the medical system is not working for you or your family?

What do you do when the physicians treating your child for a serious illness aren’t listening to your views on what is in his or her best interest?



Where is the Patient in All of This?

There are few things that frustrate me more than the system. I have come to the conclusion that there is a system that effectively keeps patients dumbed down so that they become reliant on the system and those that keep “the system” going.

Clinical trials must be conducted if new treatments are going to be developed and made available to patients. For instance, if we consider rare diseases alone, there are over 7000 rare diseases, and more are being found all the time. There are treatments for only approximately two hundred of these rare diseases.

Most patients know very little about the world of medicine, drug development, clinical trials, and development of new medicines. Unfortunately, most patients will not be offered the opportunity to enter a clinical trial even if one is available for their disease.  Even if they do find their way into a clinical trial, most will be intimidated by the process. Few will question the physician investigator or the staff working for him or her. For instance, “What side effects might I expect to experience during this clinical trial?” “How will I know if I have experienced this side effect?” “What adverse effects have previous patients in early dose groups experienced?” are all good questions to ask.  

Despite tragedies from recent past, the “system” appears to be no more effective at empowering patients, judging by recent deaths in the NHS. Because I am from the United Kingdom, I take a particular interest in what happens there. I was dismayed when the events of the TeGenero debacle came to light. Healthy volunteers had entered a clinical trial at a Phase 1 unit at Northwick Park Hospital. All healthy volunteers who received the experimental drug nearly lost their lives.   As with other similar incidents involving clinical trials, they indicated, in my view correctly, that they were not adequately informed consented. Information that should have been made available to them, was not.

Clinical Trials, What Patients and Healthy Volunteers Need to Know was published by Oxford University Press in 2010, and quite quickly made available in the United Kingdom. It is troubling that when the book has been available in the United Kingdom for over two years, the uptake of the book by the very institutions (the NHS, hospitals, Trusts, Phase 1 units, clinical trial sites) that should be ensuring that they make it available to their patients has been in a word, dismal.

I once heard another consultant say that the best client is an ignorant client. I think this is a terrible way to do business. Given this premise, I sometimes wonder if “the system” believes that the best research subjects are the ignorant ones. They don’t ask questions because they don’t know which questions to ask. They can’t therefore challenge “the system”.  Let me give some examples of why I have began to wonder about this.

The book was written in the aftermath of the UK TeGenero incident. This type of book cannot be published by a normal publisher because they consider it too much of a niche market.  This means that for a work like Clinical Trials: What Patients and Healthy Volunteers Needs to Know, the system has to be behind the work for it to reach the very people it was written for.

Sadly, the very parts of “the system” that should exist to watch out for the research subject, patient and healthy volunteer, appear to be too much a part of it to be independent from it. There is nothing more disconcerting than to be told by a patient advocacy group or Foundation that exists to serve patients with a particular disease, and collects money for this purpose, that they cannot tell their patient groups about the book because they did not write it, and they therefore cannot be seen to endorse it.  I have come to the realization that for many of these organizations the disease and therefore the patient is the means by which they raise funds. The patient often gets lost in these efforts.

Getting back to the UK, numerous organizations exist to shore up various sectors of the NHS. Many of them claim to serve a purpose that should improve patient care. Naturally, they all have management teams with very impressive titles. Recently patients died in NHS hospitals that were found to be sorely wanting. I strongly believe that an empowered patient is a patient that will intelligently question the process and is more likely to remain uninjured as a result of incompetence and negligence.  Perhaps it is time for a re-look at the institutions that exist within “the system”. The question to ask about each one is who would lose if this organization were completely obliterated?

Many of the organizations that are funded by the NHS were developed to serve the patients, but most are failing in this respect judging by the recent evidence of patient deaths within “the system”. Patients must demand that all existing organizations within the NHS, and the individuals that work for them, are held to account. These individuals must ask themselves the question, “Where is the patient in all of this?

Lorna Speid, Ph.D., is the author of Clinical Trials: What Patients and Healthy Volunteers Need to Know, published by OUP in July 2010.

Do the Horrors of the Guatemala Syphilis Study Indicate A Disregard for International Standards of Human Clinical Research In the USA?

The news that prisoners and the mentally ill were deliberately infected with syphilis and other sexually transmitted diseases in experiments conducted by the US in the late 1940s has sent shock waves around the world. What is most shocking is that this experiment occurred in the aftermath of the Nuremberg Trials which brought to light the Nazi experiments that were so abhorrent. The Nuremberg Code of 1948 set basic standards for studies to be conducted in humans. We are told that there may be 40 additional experiments yet to come to light which involved experimentation on people on US soil that were never told that they were taking part in experiments. Read more…

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