The U.S. Food and Drug Administration argues that, “American consumers benefit from having access to the safest and most advanced pharmaceutical system in the world.” The system set in place to approve pharmaceutical drugs, medications and vaccines provides for immense scrutiny of the effects of the medication on a subject well before that drug ever comes up for sale. Although the FDA and its Center for Drug Evaluation and Research do not conduct pharmaceutical testing themselves, they require testing and review data from these studies that are attached to new drug applications, or NDAs.
The system is good at developing effective pharmaceuticals, from vaccines to antibiotics. It is not good at producing those products either cheaply or quickly. One of the world’s biggest current issues is how to develop a solution to the growing threat posed by the recent Ebola epidemic in West Africa. Efforts to develop an Ebola vaccine, along with other effective treatments, have been gaining steam at research laboratories in America and across the globe.
In the past, researchers have developed an Ebola vaccine for monkeys and macaques, which are also affected by strains of the Ebola virus. The vaccine is so effective that many monkeys can be brought back to health even when injected with 100 times the lethal dose of Ebola after vaccination. However, with HIV, tuberculosis and many other diseases claiming more lives every year, research focus on Ebola has been low in recent years. So how long does it take a typical vaccine to go from concept to reality?
The Time-Consuming Nature of Clinical Trials
Yesterday we published an article explaining the extraordinary costs associated with bringing drugs to market. Today we will focus more directly on the process that leads to that the truly exorbitant costs associated with researching, developing and ultimately obtaining market approval from the FDA.
One big reason why it’s difficult to bring a new medicine to a market is that many years of research and investigation are required before an NDA is even filed, and the successful completion of clinical trials will take many more years. On average, it takes about 12 years for a pharmaceutical medication or vaccine to go from the research lab into a product that can be safely administered to human patients, according to estimates from the California Biomedical Research Association.
Once an IND has been reviewed both by the FDA and a local institutional review board (IRB), a panel of scientists and other professionals from hospitals and research institutions, clinical trials may begin under protocols established by the IRB. These protocols govern the patients that may participate in clinical trials, the objectives of the trials, the length of the study, the dosage amounts to be administered and the schedule of administering medication, among other things.
Successful medications will pass through a series of clinical trials designed to answer different questions about a drug. Phase 1 trials, administered to anywhere from 20 patients to 80 patients, determine frequent side effects and how the chemical is metabolized by a patient’s body. If there is no unacceptable toxicity in a medication during Phase 1 trials, it moves to Phase 2 trials, where the drug’s effectiveness is the focus. Although safety is still evaluated at this stage, the greater desire is to uncover data on how patients with a certain disease or condition respond to a medication versus those receiving a placebo. Phase 2 studies typically accommodate a few dozen to about 300 participants. If Phase 2 shows successful efficacy of a drug, officials from the FDA meet with a pharmaceutical company to develop Phase 3 clinical trial standards for large-scale testing. These trials can include several hundred people up to about 3,000 participants and often allows researchers to study a drug’s effects on different populations, in different dosages and in combination with other medications. All of these clinical trial phases must be successfully completed and their data attached to an NDA that is filed with the FDA for the approval of a pharmaceutical. The clinical trials period itself can last six to seven years on average.
Vaccine Development and Fear
The prevention of a wide spectrum of diseases by administering biological preparations of microorganisms meant to increase an immune response has been revolutionary for public health simply by reducing the costs incurred when treating diseases and caring for patients. It has been revolutionary in human terms by the number of lives saved, and lives significantly altered for the better. For example, polio was once terribly feared worldwide, attacking primarily children, causing paralysis for life. Thanks to two polio vaccines, the first of which was developed by Jonas Salk in 1952, the disease has been reduced by 99% worldwide.
Today there is a lot of investment by American pharmaceutical and biotechnology firms in the area of vaccine development. As of September 2013, there were 271 vaccines created by American biotechnology companies that were either in human clinical trials or under review by the FDA. The overwhelming majority of these targeted either infectious diseases (137 vaccines) or cancer (99 vaccines).
There’s been a lot of misinformation about vaccinations that has been allowed to spread despite repeated warnings on the negative health effects of missing vaccinations from public health officials, and attempts to debunk the myths about vaccines. Much of this surrounds the “theory” that vaccinations in young children could cause them to develop autism, a hypothesis that has since been disproven. Unfortunately, irrational vaccine fear prevents many parents from immunizing their children.
It is tough to overstate the connection between the development of vaccines and public health, however. Since the use of vaccinations was first introduced by English physician Edward Jenner in 1798, many devastating diseases have either been eradicated or targeted for elimination, including smallpox, measles, rubella and mumps. The CDC prominently displays these vaccine success stories on its website:
- Nearly everyone in the U.S. got measles before there was a vaccine, and hundreds died from it each year. Today, most doctors have never seen a case of measles.
- More than 15,000 Americans died from diphtheria in 1921, before there was a vaccine. Only one case of diphtheria has been reported to CDC since 2004.
- An epidemic of rubella (German measles) in 1964-65 infected 12½ million Americans, killed 2,000 babies, and caused 11,000 miscarriages. In 2012, 9 cases of rubella were reported to CDC.
With all the successes of vaccines, statistics show that even a very small presentation of the population being unvaccinated can create significant public health risks relating to a variety of infectious diseases. See Herd Immunity: History, Theory, Practice (at page 268, Table 1). This is true because vaccines don’t just protect you, they protect the public in general. This theory is known as herd immunity. The principles behind herd immunity are that if enough people are vaccinated, and therefore protected, it will be difficult for those who are unvaccinated to contract the disease. Unfortunately, there are large percentages of people who are not being immunized, particularly in the Western United States. Experts recognize that for a variety of reasons there are some people who cannot receive vaccines, perhaps due to a medical allergy. When those who can be vaccinated choose not to out of fear they are not only harming themselves, but they are harming the entire community.
Despite the universal scientific understanding that vaccines protect both individuals and entire communities, in some affluent areas like Santa Monica or Malibu, both in California, about 15 percent of kindergartners are currently unvaccinated. Eventually there will be another global pandemic, of this we can be certain. The reality that so many are fearful of vaccines coupled with the length of time it takes to create a vaccine and get it approved, as well as the lack of effective treatments for a variety of life-threatening illnesses, should be alarming to everyone. Tragically, there is no coincidence between the high rate of non-immunization and the fact that California recently experienced its highest rate of measles cases in two decades (61).
The scientific reality is that vaccines can and do work, but only if you are vaccinated.
Developing Treatments for a Growing Disaster
The incredible amount of capital that must be invested into the development of a single pharmaceutical treatment for a single disease means that drug development won’t occur without a potential market from which to profit, and there is no market without patients who are afflicted with the disease. Ebola and its effects have been known since the 1970s, but only a few thousand cases had ever been diagnosed, at least until the latest outbreak. Indeed, the current Ebola outbreak has affected a greater number of people than all other previous cases combined. Even with an increased focus on developing treatments for Ebola, the typical process for creating a vaccine or treatment would take years of clinical trials, an impossibly slow process for combating a disease that could infect 10,000 new people every week by December.
Some fast-tracking of clinical trials has been proposed to help fight in the current epidemic. For instance, an Ebola vaccine developed by the Canadian government has been provided for Phase 1 trials at the Walter Reed Army Institute of Research in Maryland. Pending successful results in those trials, Phase 2 trials could occur in Africa, possibly as early as mid-December. This vaccine, known as VSV-EBOV, and another experimental drug known as ZMapp, have both been able to reach clinical trials more quickly because of the FDA’s Animal Rule, which provides for the expedition of drug approval to fight against a pathogen that is both deadly and spreading rapidly.
It should also be noted that blood transfusions from Ebola survivors into current sufferers of the disease has been used as part of successful treatment regimens during this most recent outbreak. Most of the survivors of the disease who had been treated so far in America all received transfusions, and news reports indicate that one of the most recent recipients, American journalist Ashoka Mukpo, has begun to show signs of improvement as of the time of this writing. Transfusions have also been administered to other health workers who have become ill as a result of contact with Thomas Eric Duncan, the first patient to come down with Ebola in America. In fact, Duncan, who died from the disease, is one of the few people who did not receive a blood transfusion, owing mainly to incompatibility in blood types.
The highly developed nature of our public health system and our knowledge of the disease will most likely keep Ebola from becoming a major issue in America and many other developed nations the way it has ripped through West Africa. Still, until a vaccine or treatment that leads to the diseases eradication can be developed, the Ebola virus will prove to be a dangerous foe for health care officials and especially the workers who face the disease at the front lines of this battle.