The Cost of a Cure for Spinal Cord Injury
by Wise Young, Ph.D. M.D.
W. M. Keck Center for Collaborative Neuroscience
Rutgers University Piscataway, NJ 08854-8082
12 December 2008
In a recent post on CareCure, Random asked “What is the Cost of Cure?” This reasonable question is devilishly hard to answer for three reasons. First, the question assumes that the definition of “cure” is well-accepted. It is not. Before we can answer the question, we must agree on what the or a cure is. Second, cost depends on many factors, including where the funds are coming from, who is spending the funds, and what type of research the funds will be spent for. Third, cost depends on time. To know how much, we need to know how long it will take. Time is money.
Definition of Cure
To some people, a cure is eradication of a disease or condition. If we define cure of spinal cord injury as eradication of the condition, I don’t think that it is likely that we will be able to achieve this in the forseeable future. People are vulnerable to trauma and damage to our spinal cord will occur as long as there is bad luck or stupidity. Also, we are unlikely to develop a therapy that will restore people to the way they were before their accident. We can’t reverse aging, at least not yet.
On the other hand, it is conceivable and very likely that we will have a therapy that can restore function sufficiently so that a third party, who does not know you, would not be able to tell that you had spinal cord injury. This happens to a majority of people with so-called “incomplete” spinal cord injuries. A feasible goal of therapies is to make the person as “incomplete” as possible and allow the spinal cord plasticity to do the rest.
Let us agree that the cure for spinal cord injury is sufficient restoration of function so that a person who has not met you before could not readily tell that you had spinal cord injury. This definition does not mean that you have been restored to “normal” or even the way you were before injury. While some might disagree that such situation could be called a cure, I think that most people would agree that it is a worthwhile and feasible.
Cost of research is a complex factor that depends on the source of funds, who is spending it, and the type of research. The funding source is important because funding are seldom dedicated to one condition. For example, rehabilitation will be spread out amongst spinal cord injury and other conditions. Funding for basic science will be scattered as well.
Who is spending the funds is also important. Academic laboratories tend to emphasize basic research, with a greater likelihood of discovery and general solutions to problems. Small biotech companies tend to focus on applied science with an emphasis on proof-of-concept research for patents. Large pharmaceutical or therapeutic companies tend to do preclinical testing and clinical trials.
Research can be divided into three phases: discovery, preclinical, and clinical. Let’s say that discovery research is the least costly and one laboratory project typically costs about US$250,000 per year. Preclinical research, such as therapy development and animal testings, is more expensive, typically $2.5 million per year. Clinical trials are the most expensive, on the order of $25 million per year.
Time is a crucial factor. On average, the pharmaceutical industry estimates that it takes an average of about 11 years and $1.1 billion to move a therapy from discovery to market. The timing of the phases of research depends on the therapy and often overlap with each other. For example, the discovery phase may be 3-4 years, the preclinical phase may be 3-4 years, and the clinical phase may be 3-4 years.
The bench-to-beside time can vary from 3 years for a me-too drug which bypasses discovery and preclinical phases to over 12 years for a new drug that has to go through full-length discovery, preclinical, and clinical trial phases. Of course, complications or failures along the way mean that one must start all over, adding to the therapy development time.
Four years is quite reasonable for each phase. The discovery phase, for example, can easily exceed four years, depending on the treatment. The preclinical phase includes testing in animals and this may take several years as well. The clinical trial phase must go through the standard three phases. Phase 1 is for assessing safety and feasibility, phase 2 is for optimizing the therapy and outcomes, and phase 3 is the pivotal trial.
If a therapy requires 4 years per phase at full cost, i.e. 4 years of discovery research at $250,000/year ($1 million), 4 years of preclinical research at $2.5 million/year ($10 million), and 4 years of clinical trials at $25 million/year ($100 million), the cost adds up to $111 million per treatment. If only 10% of therapies the gauntlet, the total cost of getting a therapy to market is about $1.1 billion over 12 years.
The total treatment costs can be defrayed significantly in several ways. The first and the most important approach is to do rigorous preclinical studies that would increase the likelihood of success in the phase 3 studies. While this may add a year or two to the preclinical phase, reducing the risk of a catastrophic failure at the clinical trial phase is worthwhile.
A second and very effective approach is to have NIH-funded clinical trial networks. Such networks substantially reduce costs of clinical trials by providing already vetted and trained centers that are ready and able to test therapies. The time and expense of organizing the trials can easily waste a year and add more than 10% to the costs of the trials.
In theory, a clinical trial should have a 50% chance of success. The ethics of clinical trials require “clinical equipoise”, i.e. the probabilities that the treatment and control groups are effective should be balanced. If 10 trials were carried out, each with a 50% chance of success, the likelihood of at least one successful trial is about 95%. Thus, a program to test ten treatments has a 95% chance of yielding one therapy that works.
If the cost of one developing and testing one therapy is $111 million over 12 years, then testing ten therapies should cost about $1.11 billion over 12 years. That is about $100 million per year. If we have at least ten therapies that have passed their discovery phase and are in their preclinical trial phase, the cost and time should be less, i.e. about a billion dollars and four years.
Let us assume that NIH invests $100 million per year over the next four years into a spinal cord injury clinical trial network and that industry spends $125 million per year over the same period on clinical trials of ten therapies. If so, we have a 95% probability of having at least one positive clinical trial in four years with a $500 million investment by industry and $400 million by NIH.
Summary and Conclusions
To estimate the cost of curing spinal cord injury, I defined “cure” as a condition where a third party cannot tell that you had spinal cord injury. I then assumed that the path for each therapy involves sequential four-year phases of discovery, preclinical, and clinical research. I further assumed that discovery research has a cost of $250,000/year compared to preclinical research cost of $2.5 million/year and clinical trial cost of $25 million/year. Thus, one treatment will cost $111 million and 12 years to move from discovery to market. Finally, I assumed that it would take ten therapies to have a 95% chance of achieving a “cure”. Given these assumptions, if we were starting from scratch, it would take $1.2 billion and 12 years. However, if we already have ten therapies that are ready for clinical trial, it would cost about a billion dollar and four years. A clinical trial network would lower costs and accelerate the progress.