• Number of active U.S. SCI laboratories and scientists. If the total national funding for SCI research in 2000 is $100 million, 80% of the funding was spent on animal research, and the average laboratory requires $500,000 of research support per year, this suggests that there are about 150 funded U.S. laboratories doing SCI research. If each laboratory has an average of one and a half full-time-equivalent investigators working on SCI, this suggest that there are about 240 funded scientists doing SCI research in the U.S. This number seems to be in the right ballpark. For example, the U.S. Neurotrauma Society has about 500 members, about half of whom probably are spinal injury scientists.

• Number of U.S. SCI studies. A Medline search (see table below) indicates a total of 1049 SCI papers published in 1995; about 24% of these were animal studies and 34% were from U.S. groups. In contrast, 1430 SCI papers were published in 2000; about 33% of these were animal studies and 37% were from the U.S. groups. The number of U.S. animal studies doubled from 109 in 1995 to 218 in 2000. The number of papers published by U.S. scientists and clinicians declined in 1997 and 1998, particularly clinical papers. The number of clinical studies fell from 271 in 1995 to a low of 117 in 1998. By 2000, 177 clinical SCI papers were published. Although the 2001 Medline database is not complete, already 182 clinical papers have been published, suggesting that clinical studies are rebounding.

There is usually a 3-year lag time between increasing research funding and an increase in published studies, particularly clinical studies which may take several years to complete. The depressed output of 1997-98 corresponds to a low point of spinal cord injury funding in 1994-95 when increases of the NIH budget was barely keeping up with inflation rates. In 1996, however, Congress resolved to double NIH funding in seven years and steadily raised the NIH budget by about 15% per year, accounting for the rebound of both animal and clinical SCI papers in 1999-2001.

 Worldwide publications of SCI studies increased steadily from 1995 to 2000. This may reflect increased investment in spinal cord injury research overseas. Between 1995 and 2000, SCI publications increased from 1049 to 1430, an increase of about 36%. The number of animal studies nearly doubled from 248 to 473. The percentage of animal studies increased from 24% to 33% of total SCI publications. In the U.S., the number of U.S. animal studies doubled from 109 to 218 between 1995-2000, going from 29% of 54% of US SCI publications. In 2000, U.S. animal studies constituted 46% of the world animal SCI studies. 

Research

How can we improve the quality and pace of SCI research? One approach is to increase funding. The SCI field has been significantly underfunded compared to the cost of the condition. A second approach is to increase the number of good laboratories doing SCI research, so that they can compete successfully for governmental funds from agencies such as the National Institutes of Health (NIH). A third approach is to improve the efficiency and productivity of the laboratories, so that more research can be done with the same funding. A fourth approach is to remove obstacles that slow down movement of therapies to clinical trial.

• Increasing SCI research funding. Research funding comes from four major sources: federal, state, industry, and private. These probably totaled about $100 million in 2000 and should increase by 10-15% per year for the coming 2-3 years. However, this amount is clearly insufficient. The pharmaceutical industry recently reported that it costs $800 million to move a therapy from discovery to market. The cost of caring for traumatic spinal cord injury exceeds $10 billion. The U.S. is investing less than 1% of cost of care into research to develop solutions for SCI.

1. Federal funding. In the early half of the 1990's, the NIH budget was increased barely above inflation levels. SCI research was funded at $40-50 million per year during this period. In 1997, Congress passed a resolution to double NIH funding from $12 billion to $24 billion by 2004. Since 1997, Congress has been increasing the NIH budget by 15% every year to meet this goal. The spinal cord injury field has not been able to take as much advantage of this increase because it has not had enough scientists in the field to submit competitive grants. Spinal cord injury must compete for the funding with all the other diseases and conditions. As pointed out below, the strategy must be to increase the number of SCI investigators that can compete for NIH grants.
2. State funding. State governments traditionally do not fund research. In 1995, Florida and Kentucky were funding spinal cord injury research, providing about $1-2 million per year to support research in the state. In 1998, New York State passed legislation to add a $15 surcharge to speeding tickets, providing some $8-9 million per year for spinal cord injury. In 1999, New Jersey passed legislation to fund $3-4 million per year from a $1 surcharge on all traffic tickets. California, Indiana, Illinois, Oregon, Missouri, Connecticut, and several others states have passed similar legislation. About a dozen other states have pending legislation. State funding provides critical support for new laboratories starting SCI research until they can compete successfully for NIH funding.
3. Industry funding. The pharmaceutical industry is potentially the largest source of research funding. The top ten pharmaceutical companies each spend $2-5 billion each on research and development. Their investment far exceeds those of all the other sources combined. Unfortunate, they have been reluctant to invest in SCI research because of the widely held perception that SCI is a small market. However, industry funding of SCI research is building up rapidly. In 1996, only two companies were seriously investing in SCI research (Fidia Pharmaceuticals and Acorda Therapeutics). Over a dozen major companies are now investing in SCI research (Novartis, Aventis, Biogen, Neotherapeutics, Diacrin, Boston Life Science, Alexion, Regeneron, Advanced Cell Technology, Proneuron, and Geron). Clearly, there is room for growth.
4. Private foundations. Several major private foundations support SCI research. The two largest is the Christopher Reeve Paralysis Foundation (formerly the American Paralysis Association) and the Paralyzed Veterans of America. Many other foundations are raising money for SCI research, including the Kent Waldrep National Paralysis Foundation, the Danny Heumann Fund, the Alan T. Brown Foundation, the Spinal Cord Society, and others. In addition, regional groups such as the Miami Project and the SCI Project at Rutgers raise funds for research. Not counting expenditures such as $30 million for the Miami Project building, these groups are probably raising and spending about $20 million per year on SCI research. Private foundation funding for SCI research is relatively small compared to other neurological conditions such as Multiple Sclerosis, Parkinson's disease, and Alzheimer's disease. However, private funding of neurological research pales into insignificance when compared to AIDS funding which is on the order of hundreds of million.

• Increasing the number of competitive SCI laboratories. It is not sufficient to increase research funding when there are not enough good scientists working in the field. For example, as pointed out above, the spinal cord injury field has not been able to take full advantage of the increase in NIH funding because there are not sufficient good spinal cord injury laboratories that can compete successfully for NIH funds. In order to take advantage of the doubling of funding, we must double the number of laboratories in the field. Note that state and private foundation funding are very useful for attracting scientists to enter the field and supporting them until they can compete successfully for federal funding. NIH can help if they established a series of Centers of Excellence to help generate new scientists and laboratories for the field.

• Improving efficiency and productivity of the field. Another way to improve the quality and pace of SCI research is to increase the efficiency and production of the laboratories. SCI studies are very laborious and time-consuming. The experiments take a long time and are expensive. If it is possible to develop surrogate measures or models that allow treatments and mechanisms to be studied more efficiently, the productivity of the field can be markedly increased. For example, if regeneration associated genes (RAGs) are identified, it may be possible to screen therapies for changes in gene expression rather than waiting 3-6 months for the regeneration to take place and then go through the time-consuming morphological analyses of the spinal cords to demonstrate regeneration. Likewise, having a good spinal cord injury model that is consistent and reproducible from laboratory to laboratory could markedly reduce the number of experiments that must be carried out in order to demonstrate treatment effects. Finally, it would be useful for laboratories to collaborate and share data, reducing unnecessary duplication and allowing meta-analyses to be carried out on data across studies and centers.

• Moving therapies rapidly to clinical trial. In the United States, clinical trials are expensive and time consuming. In a typical clinical trial, each subject costs $30,000-$50,000 and a trial may require 2-3 years to complete. If a company is running the trial, there are additional costs for audits of the data collection and analyses, reporting to the FDA, etc. A small phase 2 trial may cost $5-10 million while a larger pivotal trial may cost $10-$30 million. Such costs are obviously not trivial and must be funded either by a pharmaceutical company or the federal government. Inability to find a sponsor often delays promising therapies for years or even decades. There is also a shortage of clinicians who are trained and inclined to run and participate in clinical trials. Some treatments such as cell transplants require multidisciplinary clinical teams, including neurosurgeons, intensivists, radiologists, physiatrists, nurses, physical therapists, and others. Establishing such a clinical trial team may take years. Finally, recruitment of subjects for clinical trials, particularly trials that involve randomization to placebo treatment, may be difficult and often take a long time. One solution to these problems is for the Federal government to establish a network of SCI clinical trial centers. Having centers that have multidisciplinary teams already set up to do clinical trials, that have access to a sufficient population of willing subjects , and that can care for and evaluate the subjects efficiently will greatly reduce the time needed to organize and execute clinical trials.