F.A.Q.
Why Do We Need Clinical Trials?
The Story of ChinaSCINet and SCINetUSA
Why Do Clinical Trials Cost So Much?
Why Do We Need Clinical Trials?
People are always asking why we need clinical trials. They say, “Why don’t we just go ahead and treat people with whatever seems promising?"
Clinical trials are critical to finding a cure. They are the way to provide concrete evidence of whether or not a therapy is effective. Because of this, clinical trials are the only way a therapy will receive regulatory approval and therefore the only way a therapy will be accepted by other doctors and the only way insurance companies will pay for the treatments.
When so-called ‘treatments’ are done overseas by doctors who are charging for the therapy, they cannot do the randomized trials necessary to prove that the therapies are safe and effective. Those who charge for the therapies become dependent on the money and never show whether or not the therapy is effective.
Clinical trials provide impartial and objective information concerning therapies. Therefore clinical trials should be carried out by impartial investigators who have ‘no skin’ in the deal. This is why it is important for a therapy to be supported by two or more third party investigators before being accepted for clinical trials.
The line between science and quackery is very sharp and clear. Clinical trials provide strong and credible evidence that a treatment is safe and effective. A quack may claim a cure but does not provide credible evidence for safety and efficacy. Quacks sell unproven therapies, using testimonials as their primary support. Many testimonials have proven to be false and misleading. If someone has paid for a therapy, they want to believe it works. This is the reason ChinaSCINet and SCINetUSA emphasize that the first trials may or may not show that umbilical cord blood mononuclear cells and lithium work. If they don’t work, that information will be public.
Multiple clinical trial networks are needed. For example, with cancer, hundreds of clinical trials are carried out every year. Nearly 50% of people with cancer have the opportunity to be randomized in clinical trials. This compares with less than 0.1% of people with spinal cord injuries. Clinical trials are like seeds. The earlier and the more seeds are planted, the earlier and bigger the harvest.
Only clinical trials provide the evidence of safety and efficacy needed for a treatment to get regulatory approval and be accepted by doctors and insurance companies. And that is the only way genuine treatments will come to people.
Before becoming available as a treatment, drugs and cells that show promise in laboratories must undergo rigorous testing in a clinical trial. A clinical trial is an organized system to test the safety and effectiveness of a proposed treatment. A clinical trial usually consists of a network and several clinical institutions. The network is responsible for the organization, administration, development of protocols, training, and government approvals needed for the trial. The individual institutions evaluate and select the trial participants and conduct the treatments based on previously approved protocols.
A clinical trial consists of three phases:
Phase 1 is to test the safety of the proposed treatment. It includes a limited number of participants who are given the treatment to see if there are any side effects.
Phase 2 is to test the efficacy of, and to optimize, the treatment. Phase 2 trials involve a comparison between groups receiving different treatments and are conducted on with a small number of participants.
Phase 3 is a broader test of the optimized treatment on a larger number of people. It involves the optimized treatment compared with other options and usually is conducted at multiple centers.
Should you participate in a clinical trial?
Volunteering to participate in a clinical trial is not something you do for yourself; it is something you do as service to the community. It isn’t about getting to be first in line for a new treatment. It’s about being willing to weigh risks as well as potential benefits so that potential treatments might be proven to be effective. It is a way to learn so that they might be improved for future trials. It also is a way of finding out that things which might appear promising in laboratories don’t work in people. This also is a valuable lesson as it allows time and resources to be directed into more promising avenues. A negative result also closes down those who charge people with false claims. Top
The Story of ChinaSCINet and SCINetUSA
In 1998, Sang Lan, a young Chinese gymnast broke her neck in the Good Will Games in New York City. Her parents flew from China and, even before they went to the hospital, they came to Rutgers and asked the questions all parents ask: “Is there hope? Will there be a cure?” I told them I believed there would be a cure and that we were working hard to make it happen. In 1999, before Sang Lan returned to China, we held a dinner in Chinatown for her. At the dinner she cried. I asked why. She replied, "If you discover the cure in America, how will it come to China?” I told her that doing clinical trials in China was the only way and promised her I would do my best to make it so.
In 1999, I went to China where I gave a series of lectures for Pfizer to encourage Chinese doctors to use the drug methylprednisolone for spinal cord injury. In 1990, my colleagues and I had shown that this drug improves neurological recovery when given within eight hours after injury. In 1999, China was still a nation of bicycles that swarmed every intersection while cars inched along. Spinal cord injury was relatively rare, about 6.5 cases per million compared to 35 cases per million in the U.S. Due to limited emergency services and post-injury care, many people died.
For the next four years I went to China several times a year, giving lectures to doctors who treated spinal cord injuries, telling them of promising therapies that restore function in animals, and exhorting them to do clinical trials. In 2003, the mother of a spinal injured teenager from Hong Kong offered to pay to cure her son. Dr. Young asked her to help him establish a spinal cord injury clinical trial network in China. She introduced him to Paul Tam, pro-vice-chancellor of Hong Kong University Medical School, and Vice-Minister of Health Huang Jifu in Beijing. Professor Tam offered the support of Hong Kong University and Minister Huang gave his blessings to start a clinical trial network, urging that ethical research be done.
2004, the heads of the top spinal cord injury centers in China were invited to meet at Hong Kong University. Fifteen came to this unprecedented meeting and agreed to work together to form the first clinical trial network in China. Dr. Young took a year’s sabbatical to organize ChinaSCINet. In 2005 Dr. Wutian Wu, a professor at HKU and Dr. Young visited all the centers. Each signed research contracts to participate in joint clinical trials. In December, the first International Spinal Cord Injury Treatment and Trials Symposium was held in Hong Kong.
A fundraiser was held which included Richard Gaskin of New Jersey, known professionally as ProfessirX. The audience was riveted by his “Forever Superman” a moving tribute to Christopher Reeve who tragically had just died. Sang Lan sang a lovely Chinese folk song. It was unlike any other fundraiser and was the beginning of ChinaSCINet.
From 2006 to 2007, four meetings were held each year to train the doctors in standardized neurological examinations and clinical data collection. A group of investigators was brought to the Keck Center to learn the rat spinal cord injury model, so they could conduct research. What ChinaSCINet has accomplished is already worth the investment of time, effort, and money. In two years, standardized neurological examinations of spinal cord injury were brought to China and spinal injury doctors worked together, trusted each other, and have begun to collaborate. There now are 25 centers in mainland China, Hong Kong, and Taiwan.
In 2007, the decision was made on the first therapies to be tested in ChinaSCINet. At that time, there was only one source of well-documented cells available in sufficient numbers and diversity to be HLA-matched so the cells would not be immune-rejected. That was umbilical cord blood cells. Many laboratories had reported that these cells improved recovery in animals after spinal cord injury. Colleagues at Hong Kong University discovered that lithium, a drug long used to treat manic-depression, stimulates regeneration and promotes growth and neural differentiation of neural stem cells in the spinal cord. At the Keck Center, a student team discovered that lithium stimulates umbilical cord blood cells to grow and produce neurotrophins which promote regeneration. Thus, it was decided to study umbilical cord blood mononuclear cells and lithium treatment of chronic spinal cord injury in ChinaSCINet.
In 2008, a phase 1 trial of a 6-week course of lithium in twenty patients with chronic spinal cord injury was completed. Although seven patients dropped out, the drug clearly was safe and did not produce any significant adverse effects. In 2009, a phase 2 trial randomizing 40 patients with chronic spinal cord injury to a 6-week course of lithium or placebo was completed. Only 2 (5%) of the patients did not complete the study.
(This trial showed an unexpected result: Lithium markedly reduced neuropathic pain. Spinal cord injury not only causes paralysis and sensory loss but also causes spasticity, increased excitability of the body below the injury site, and neuropathic pain, hypersensitivity to minor stimuli and spontaneous pain. Lithium not only reduced neuropathic pain during the time the drug was given but the pain remained less for six months.)
A phase 2 trial is now underway in Hong Kong to assess escalating doses of umbilical cord blood mononuclear cell transplants in 20 patients with chronic spinal cord injury. Four, eight, and then sixteen µliters of 1.6, 3.2, and 6.4 million mononuclear cells are being injected into the spinal cord above and below the injury site, using a new imaging method called diffusion tensor imaging (DTI) to find the injury margins. Animal studies suggest that cells injected into the middle of injury site, just form an isolated island. However, cells injured at the injury margins, migrate into, and form a bridge across the injury site.
Word quickly spread in the United States that these trials were being done in China. At a Fall 2008 meeting at Magee Rehabilitation Center in Philadelphia, two large rooms overflowed with people interested in learning about ChinaSCINet. Many asked how they could go to China. This is unacceptable. People shouldn’t have to go to China to participate in clinical trials of therapies developed in the United States? Umbilical cord blood cells and lithium aren’t controversial. The only obstacle is money.
San Lang’s innocent question about how the cure was going to get from the U.S. to China has come full circle. Now Americans were clamoring to participate in clinical trials in China. Something had to be done.
So, in 2009, a spinal cord injury clinical trial network was established in the United States. Eight centers are working with the Protocol Committee, including several of the best spinal cord injury centers in the United States. The flagship hospital is Brackenridge Hospital in Austin, Texas. Governor Rick Perry gave a warm welcome to Texas and the legislature presented a Texas flag that flew over the capitol when they passed a resolution to praise SCINetUSA. Top
Why Do Clinical Trials Cost So Much?
In the United States, hospitalization and medical care are expensive. To admit a person to a hospital, do all the tests, carry out surgery to inject cells into spinal cord, and keep the patient for two days costs about $50,000. Three months of intense locomotor training, even with volunteers, will cost $50,000 or more. The first SCINetUSA trial will assess 240 patients (four groups of 60 patients, treated with rehabilitation alone, rehabilitation plus lithium, rehabilitation plus umbilical cord blood mononuclear cell transplants, and then rehabilitation plus the transplants and lithium). The cells cost $22,000 but are being donated by Stemcyte, Inc. Top
JustADollarPlease.org is the fundraising arm of SCINetUSA. One of the Moms said, “If we can’t find a millionaire, we will ask a million people for a dollar.” And so JustADollarPlease.org was born.
Friends of spinal cord injury research will be asked to forward an email to all of their friends and ask them to keep the chain going. People can give a dollar, a dollar a month, a week, or whatever they choose. Schools and clubs can hold special events. Businesses can be asked to put out collection jars. People can celebrate birthdays and anniversaries with dollars in lieu of gifts.
Families who know about spinal cord injury first hand and their friends are invited to join the ‘Special Support Squad’ by donating a dollar a day towards trials for chronic injuries. There are over 1.3 million families in the United States who deal daily with spinal cord injury. If 10,000 families gave a dollar a day, that would be $3.65 million per year. Called http://JustADollarPlease.Org, this campaign even has its own rap song, sung by our own ProfessirX, Richard Gaskin.
We not only can but must do this. For too many years, people in wheelchairs have sat patiently and waited for government, for industry, and for wealthy people to fund the cure. Year passed, decades passed, and pitifully little happened. Many have given up. Christopher and Dana Reeve died and everybody is sorry but while others go on with their lives, people continue to be in their wheelchairs.
The travesty is that many therapies are regenerating spinal cords and restoring function in animals but so few have gone to clinical trials. With JustADollarPlease.org you can help make this happen. Top
Richard H. Shindell Chair in Neuroscience
Dr. Wise Young, founding director of the W.M. Keck Center for Collaborative Neuroscience and a professor at Rutgers, The State University of New Jersey, is recognized as one of the world's outstanding neuroscientists. He obtained a bachelor of arts degree from Reed College, a doctorate from the University of Iowa and a medical degree from Stanford University. After a surgery internship at New York University and Bellevue Medical Center, he joined the neurosurgery department at NYU. In 1984, he became director of neurosurgery research. In 1997, as part of Rutgers' commitment to the future, Dr. Young was recruited to establish and direct a world-class center for collaborative neuroscience.
Dr. Young was part of the team that discovered and established high-dose methylprednisolone (MP) as the first effective therapy for spinal cord injuries. This 1990 work upended concepts that spinal cord injuries were permanent, refocused research, and opened new vistas of hope. This team also played a major role in Andy Blight's signal work on 4-aminopyridine (4-AP), which shows significant promise for increasing nerve conductivity.
Dr. Young developed the first standardized rat spinal cord injury model used worldwide for testing therapies, formed the first consortium funded by the National Institutes of Health (NIH) to test promising therapies, and helped establish several widely accepted clinical outcome measures in spinal cord injury research.
Dr. Young founded and served as editor-in-chief of the Journal of Neurotrauma. He organized the National and International Neurotrauma Societies as forums for scientists to share discoveries and collaborate on spinal cord injury and brain research. He serves or has served on advisory committees for the NIH, the National Academy of Sciences, and NICHD, and has served on advisory boards for many spinal cord injury organizations.
Well-known as a leader in spinal cord injury research, Dr. Young has appeared on "20/20" with Barbara Walters and Christopher Reeve, "48 Hours," "Today," "Eye-to-Eye," Fox News and CNN's news magazine with Jeff Greenfield. His work has been featured in a Life magazine special edition, in USA Today, and in innumerable other news, talk and print presentations throughout the world. His honors include: NIH Jacob Javits Neuroscience Award (1985-1992), Wakeman Award (1991), Tall Texan of the Year Award (1997), "Cure" Award (1998), Trustees Award for Excellence in Research (2001), 2002 Asian American Achievement Award, Douglass Medal for work with the advancement of young women in the sciences (2003), and Elizabeth M. Boggs Award for service to the disability community (2004). In August 2001, TIME Magazine named Dr. Young as ‘America’s Best’ in the field of spinal cord injury research. In 2005 he was the first researcher elected to the Spinal Cord Injury Hall of Fame. In 2006, Dr. Young received The Hope Award – A Salute to Research Innovation, the New Jersey Educator of the Year Award, and the Caring Heart Award. Also in 2006, the Richard H. Shindell Chair in Neuroscience was established at Rutgers University and Dr. Young was named as the first person to hold that chair. In 2007 the Motolinsky Foundation named Wise Young as the recipient of their Distinguished Citizen Award.
As part of his commitment to bring treatments to people with chronic spinal cord Injuries, Dr. Young has built and trained a twenty-five center clinical trial network in China, Taiwan, and Hong Kong. He presently is in the process of establishing a clinical trial network in the United States. Top
From Dr. Wise Young
Thank you everyone for all you have done and continue to do to make clinical trials and effective therapies a reality.
Wise Young, M.D., Ph.D., Founding Director
Richard H. Shindell Chair in Neuroscience
