Measles Madness And Value: Gene Therapy, Prevention, And The Pre-Vaccine Era

Measles Madness And Value: Gene Therapy, Prevention, And The Pre-Vaccine Era
Angela K. Shen
June 12, 2019 – Health Affairs Blog

The value of keeping healthy through prevention is often distorted relative to the value treatment offers individuals who are suffering devastating illnesses. Vaccines have long been used in the arsenal of public health tools to save lives, more lives than any other medical intervention, including antibiotics or surgery. Vaccines also prevent disability such as blindness and paralysis that can be caused by diseases.

Therapeutic medicines, including groundbreaking treatments such as gene therapy, treat and potentially cure conditions, representing a paradigm shift in quality of life for those suffering from a wide range of diseases. The distortion in valuing vaccines stems in part from the fact that—in contrast to the highly visible diseases treated through gene therapy—much of society today has not experienced or witnessed the death and disability caused by now vaccine-preventable diseases. However, recurrent measles outbreaks in the United States (Oregon, Washington State, and New York) have charged the increasing discourse over vaccination.

While the majority of individuals accept vaccination, many outbreaks are fueled by unvaccinated children and adults who are hesitant, reluctant, or refuse to be vaccinated. In between are individuals, undecided about vaccination to varying degrees, including those perhaps uneasy that the right and freedom to choose vaccination for themselves and their children are subsumed by state vaccination requirements for daycare and entrance into school. Understanding the factors that impact these individuals’ decision to vaccinate or not is important and may help illuminate which direction these undecided individuals may be moving toward.

The Canary In The Coalmine And The Vaccines Bargain
Measles outbreaks, such as those occurring in the United States and elsewhere today, are often called the “tip of the iceberg” and serve as the proverbial “canary in the coalmine,” warning of danger to come. These outbreaks signal to public health experts that the herd immunity protection of vaccines afforded to the community is weakened because not enough individuals in the community are vaccinated.

Vaccination, a generally one-time administration of a Food and Drug Administration (FDA)—approved biologic, is a bargain. In the United States, the cost of vaccines range approximately from $9 to $158 per dose, with an additional average $20 paid to the provider for the administration of the product. National recommendations provide guidance for use of vaccines to prevent or eliminate 17 vaccine-preventable diseases, namely diphtheria, pertussis, tetanus, poliomyelitis, measles, mumps, rubella (including congenital rubella syndrome), influenza, invasive Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, rotavirus, varicella, herpes zoster (shingles), and disease caused by many of the most important types of Streptococcus pneumoniae, Neisseria meningitides, and human papillomavirus (HPV). Vaccines on the US pediatric immunization schedule protect children from 14 vaccine preventable diseases by age two, when children are most vulnerable. Each US birth cohort of approximately 4.3 million children vaccinated with the 2009 routine childhood immunization schedule translates to preventing approximately 42,000 deaths and 20 million cases of diseases, and a net savings of nearly $14 billion in direct, and $69 billion in total, societal costs.

Vaccination of adults similarly yields reduced illness and costs. In 2015, common vaccine-preventable diseases in adults cost the US $9 billion, with 80 percent of costs from those who did not get vaccinated. Additionally, two vaccines are readily available to combat cancer. Liver disease is caused by the hepatitis B virus (HBV), and the hepatitis B vaccine is available for all age groups to prevent HBV infection. The human papillomavirus (HPV) vaccine is a vaccine on the US adolescent immunization schedule that protects against the HPV types that most often cause cervical, vaginal, vulvar, and anal cancers.

The US government invests significantly in the purchase of vaccines and in public health safety-net programs for administration of Advisory Committee on Immunization Practices (ACIP)-recommended vaccines. For example, to ensure all children have access to vaccines without financial barriers, the federal government purchases approximately half of the pediatric supply of vaccines, amounting to more than $4 billion. Vaccines are considered a public health good and protect not only vaccinated individuals, but those in the community who may not be able to be vaccinated (for example, the immunocompromised). Because of the Affordable Care Act, all ACIP-recommended vaccines must be covered by insurance at first dollar (that is, no cost sharing in the form of copayments, deductibles, or co-insurance) in most insurance plans to facilitate access to vaccinations for all individuals. Investments made in vaccines reap an exponential return.

Groundbreaking Gene Therapy
In the burgeoning and newer field of gene therapy, groundbreaking single-treatment cures are increasingly becoming available for a wide range of challenging and life threatening diseases ranging from hemophilia, sickle-cell disease, blindness, and serious inherited neurodegenerative disorders to an array of other genetic diseases and multiple cancers. Many of these conditions are rare, affecting a handful of patients.

Like vaccines, gene therapy is a one-time treatment, a single dose or infusion. However, unlike preventive vaccines these biologics are therapeutic treatments of disorders. Gene therapy products replace or inactivate a faulty gene or add a new gene. These innovations, like other medical innovations, have potential risks such as toxicity, inflammation, and cancer. Tolerance for these risks, under therapeutic conditions is high, particularly for serious and life-threatening conditions.

Priced comparable to several years of therapy for the given disorder, gene therapy treatments are expensive. Prices range from $850,000 for a gene therapy treatment for an inherited retinal disease (nearly all patients progress to complete blindness) that affects only 1,000–2,000 people in the United States, to an estimated expensive but cost-effective $2.125 million gene therapy treatment recently FDA-approved for spinal muscular atrophy, a fatal disease affecting infants. One-time treatments for gene therapy are arguably more valuable then thousands of dollars in treatments annually. Similarly, for vaccinations, as embodied in the famous Benjamin Franklin quote “an ounce of prevention is worth a pound of cure,” preventing disease, disability, and discomfort from vaccine-preventable diseases often takes less effort than treating them.

Reconciling Value
Society’s willingness to pay varies for prevention and treatment. Individuals and society value these two types of interventions differently in part due to perceptions of risk, probability, and severity of disease. Decades of research and development and centuries of scientific inquiry and observation, including hundreds and thousands of failed candidates, have yielded successful pediatric, adolescent, and adult vaccines. Yet, because we have nearly eliminated the evidence of and suffering from these diseases (for example, paralysis and lockjaw), consumers today can easily take vaccines for granted. In 2017, an unvaccinated boy was hospitalized for tetanus for 57 days, and the cost of his care approached a staggering $1 million. The cost of a tetanus vaccine is $30 a dose, and the full series requires five doses.

The valuation of health interventions is confounded if consumers do not have a clear understanding of the risks of vaccine-preventable diseases and the likelihood of contracting one. Consumers value staying healthy proportionally to the risk of dying, reflecting their assessment of how common a disease is. A low perception of harm from vaccine-preventable diseases, in part, has fueled the development of vaccine hesitancy, leading the World Health Organization to deem vaccine hesitancy a top 10 threat to the world in 2019.

The irony is that if vaccine refusal increases, previously low vaccine-preventable threats will re-emerge to remind us of a time before widespread implementation of vaccine recommendations, a time when an estimated average of 29,005 cases of smallpox (1900–49), 530,162 cases of measles (1953–62), and 185,120 cases of pertussis (1934–43) burdened our society. The death tallies during the periods noted from these now-preventable diseases averaged 337, 440, and 4,034 respectively in the pre-vaccine era. The canary is clearly singing, loudly warning of a true public health crisis at our global doorstep.