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.

Funds

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

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.

Cost

If a therapy requires 4 years full cost per phase, 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), assuming success in all phases, the cost adds up to $111 million per treatment.  If only 10% of therapies pass all phases, the total cost of getting a therapy to market is about $1.1 billion.

The total treatment costs can be defrayed significantly in several ways.  The first and the most important approach is to do more rigorous preclinical studies and 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 very wortwhile.

A second and very effective approach is to have NIH-funded clinical trial networks.  Such networks substantially reduce the cost of clinical trials by providing companies with already vetted and trained centers that are ready and able to test therapies continuously.  Instead of costing $25 million a year, a network may halve the cost of clinical trials because so much of the cost and delay is having to organize the trials from scratch every time.

Probability

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 on therapy is $111 million over 12 years, then testing 10 therapies may cost as much as $1.11 billion over 12 years.  If clinical trial costs were halved, the total over 12 years would be $610 million rather than $1.11 billion. The costs are even lower if we consider that at least ten therapies and combinations have passed their discovery phase and are almost ready for clinical trial.

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 that are currently in preclinical phase.  If so, we have a 95% probability of having at least one positive clinical trial within the coming four years with a $500 million investment by industry and $400 million by NIH.

Summary and Conclusions

Estimating cost of a “cure” requires definition of “cure”, the funds available, and the time course.  We defined “cure” as a condition where a third party cannot tell that you had spinal cord injury.  Discovery research is typically low cost of $250,000/year versus preclinical research of $2.5 million/year and clinical trials of $25 million/year.  Four years of estimated clinical trial costs for ten therapies would be $250 million per year.  Total investment in the U.S. would be about a billion, i.e. $400 million from the federal government, $500 million from the industry, and perhaps $100 million from donations and foundations.  All the above assumes that we are lucky and the trials work out the way we hope.