The problem with people paying for experimental procedures and doctors who accept such payments is conflict of interest. Neither the people nor the doctors have any incentive to say that the procedure does not work when it doesn't work. When doctors are making a lot of money and people are paying the money for experimental therapies, the temptation to keep doing it is almost irresistable. It takes a very strong and ethical doctor to say no.

People who pay money for an experimental procedure want the procedure to work. They are invested. Even when nothing is happening, they hope that something is happening. That combination of the doctors wanting the procedure to work and the patients wanting the therapy to work makes it almost impossible to evaluate whether the therapy really works.

The above is human nature. I don't think that we can do much to change that. On the other hand, it clearly indicates the need for rigorous clinical trials to test the therapies.

Paolo,

Thank you very much for your thoughtful (and provocative comments). Let me take the last comment first. Clinical trials are relatively new in medicine. When I graduated from medical school in 1977, they described what I was about to embark on as "the Art of Medicine", not the science of medicine. We were taught to take care of our patients the best that we can, use the most promising therapies, and innovate in our care of people. That attitude has changed. Since 1977, the practice of medicine has become one that is based on delivering the standards of care, negotiating with insurance companies for what therapies will be reimbursed, and practicing defensive medicine.

For most of human history, people traveled to famous doctors or treating clinics, to get "cures". It was all based on reputation of the doctors or clinics, rather than evidence of efficacy. In places like India and China, reputation rather than evidence is what attracts people to doctors and hospitals. For example, I heard of a doctor in Ahmedabad who has been transplanting kidneys into people after immunotolerizing them with some kind of injection of cells and he does not use immunosuppression at all. Apparently, this doctor (who works in a government hospital) has not published his results nor the method but is doing thousands of transplants. I was stunned by this. Based on everything that I know about kidney transplants, this is a recipe for organ rejection and death of the patients. When I ask whether anybody knows the mortality and morbidity rates of this procedure, nobody knew.

Geeta Shroff is a doctor in New Delhi who has been treating spinal cord injury and other neurological diseases with intramuscular injections of cells that she claims are human embryonic stem cells. She has not published any of her work. She has submitted a patent on primary human embryonic stem cells but this is apparently not what she is using to treat the patients. There is no verification that the cells that she is using are embryonic stem cells. Doctors in Delhi and from Bombay have told me that she has treated thousands of patients, charging them $30,000 to $80,000 for unproven therapies. This is what happens in a world where reputation-based medicine holds sway.

A number of other doctors have been delivering experimental therapies for spinal cord injury and charging for the therapies. For example, Carlos Lima, Hongyun Huang, and before them Carl Kao with his peripheral nerve transplants and Harry Goldsmith with his omentum transplants, have treated thousands of people with spinal cord injury. While Lima and Huang have been trying to publish their results, Kao has not. But, all charged the patients for experimental therapies and none have provided convincing data that their therapies are effective. If we include patients treated by Beike Biotechnology (who apparently has been treating 2 spinal-injured patients a day for several years), the X-Cell Center in Cologne, the Tijuana Clinic which transplanted shark embryos in hundreds of patients, and Caribbean and Mexican centers that have infused umbilical cord blood into hundreds of people with spinal cord injury, often for $20,000 or more, we are talking about tens of thousands of patients.

Let's say that these doctors and clinics have treated 20,000 people with spinal cord injury over the past decade and charged these patients an average of US$20,000 each for the treatments. That comes to $400 million. What has this investment by the spinal cord injury community gotten us? Do we have any convincing evidence that these therapies work? Have we convinced any insurance company or government to cover these therapies? Have we spared any family the agony of paying their life savings for therapies that don't work? Have we gained anything? I submit that the answer is no. That is why we need rigorous clinical trials. Please understand that every one of these doctors believe fervently in their therapies. Their therapies may actually have some beneficial effects. But, we don't know and have had no progress.

6-Shooter,

Let me try to answer the question: "How will you know how much the mind helped or did not help the healing process during the trials...?"

First, well-known and validated outcome measures should be used. We have such measures. The American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCOS) have agreed on the International Classification System of A, B, C, D, and E, as well as motor and sensory scores. To assess pain, there are numerous scores, including the visual analog scale. To assess spasticity, there is the modified Ashworth scale. To assess independence, there is the Spinal Cord Independence Measure.

Second, the trials need to be randomized between treatment and a control. By the way, control does not necessarily mean placebo. A placebo is an ineffective drug (such as sugar). The most meaningful and ethical clinical trial comparison is best standard therapy compared to the experimental therapy. Subjects need to be randomized to these therapies. Furthermore, they must agree to be examined and to come back for the followup examinations.

Third, double-blinding of the treatments is necessary. Patients should not know or be able to tell which treatment they received. Knowledge that they received an effective therapy or no effective therapy may have a large effect on the response to therapy. Many studies have shown the placebo and or nocebo have powerful effects on the patients. For example, if you tell the patients that the treatment is bound to work, most patients will tell you that they are better.

Now, let me give you the specific examples of the planned phase 3 UCBMC trials that we are planning to carry out in China and in the United States. In China, we are planning to study 400 subjects (A, B, and C). All the subjects will receive cord blood cell transplants. Half will then receive lithium for 6 weeks and half will receive placebo. Three outcomes of the trial is possible.

1. If neither treatment group shows significant improvement of neurological scores at 6 and 12 months after injury, compared to pre-treatment levels, we can safely claim that the treatments are ineffective.
2. If both treatment groups show significant improvement of neurological scores at 6 and 12 months, compared to pre-treatment levels, this would suggest that umbilical cord blood cell transplants are beneficial. To rule out a placebo effect, we would need to do a placebo-controlled trial.
3. If only the transplant plus lithium is effective and the transplant alone is not, we would be able to conclude that transplant plus lithium is more effective, because this was a double-blind randomization.

Chasb,

The solution that you suggest, i.e. getting a standardized examination of all patients who pay for experimental therapies, is not and will not work, in my opinion, for the following reasons:

1. Unreliable data. Not everybody who get the treatment will get a standard outcome measure done by somebody who is trained and can carry out the measure. I remember asking people to go to their doctors to get examined before and after they went to Hungyun Huang to get fetal OEG transplants. Some people sent me the results. In many cases, the doctors they found to do the examination did not do the examination properly. In a well-run clinical trial, doctors are trained to do the examinations and tested to ensure that they are doing it right. All data collection is supervised and approved, and checked by an independent party. It would be nice if this were done but it is seldom, if ever, done. Wayne State University and the Rehabilitation Institute of Michigan actually offered a program where people can go to them and get themselves examined before and after experimental therapies. I am not sure that this program is yielding reliable data but it has the potential to do so.
2. Placebo effect. Such self-paid trials are never placebo-controlled, for obvious reasons. In other words, there is no randomizatipon of people to placebo (no treatment) or best standard therapy for comparison against people who receive the experimental therapy. Placebo effects are quite strong and contribute to real improvements in some patients. In addition, the placebo effect (i.e. belief the the treatment is of benefit) often motivates the patients to exercise and work harder at locomotor and other effects. While placebo effects are good, it does not indicate that the treatment itself is the reason for recovery. Please note that surgery itself has very strong placebo effects.
3. Conflict of interest. Despite their best intentions, both the subjects and the doctors have a major conflict of interest. Because the subjects have paid for the experimental therapy, they want it to work. The more they have paid for it, the more they want it to work. This is also true of the doctors. The more the doctors come to depend on the income, the more they want it to work. In other words, neither the subjects nor the doctors can be objective about the treatment effects. Third parties must be used to assess the treatment effects. This is seldom done.

On the other hand, one can strongly argue that any therapy, even a placebo, if it restores function, must be good for the subject. Why not? Why not create an environment that maximizes the placebo effect of the therapy? Does it matter whether the effect of the treatment is due to the treatment or to a placebo effect?