If you’ve been in an old European castle with spiral stairs, then chances are the spiral stairs had a left-handed rotation (i.e., ascended clockwise). This is commonly explained by the military advantage it gave defenders and the disadvantage it handed attackers (assuming both were right-handed). When using a sword or other weapon in their right hand, defenders from above would have more space, whereas attackers from below would have less space to wield their weapon. Arguments to debunk this theory have typically pointed to instances of surviving castles with spiral stairs that have a right-handed rotation (i.e., ascended counterclockwise). Some naysayers of the military explanation point to a study of surviving spiral stairs in old castles by Charles Ryder, who found that approximately 30% had a right-handed rotation. However, if there were no directional advantage, then we might expect an approximate 50/50 split between right- and left-handed spirals.
Let’s now turn to another important spiral. Interestingly, DNA’s double helix is right-handed, and this orientation likely provided a defensive advantage. The Vester-Ulbricht hypothesis posits that the primarily left-handed spinning electrons in cosmic beta radiation could have destroyed left-handed DNA precursors in the primordial soup, with only right-handed DNA surviving. About 10 years ago, physicists demonstrated that left-handed electrons preferentially destroy left-handed molecules, a finding that supports the Vester-Ulbricht hypothesis. The fact that 100% of surviving organisms on earth have right-handed DNA suggests this was due to natural selection whereby only the fittest double helix structures survived.
It turns out that both spiral stairs and the double helix help to explain the evolution of step therapy and predict its future.
Attack and defend
Step therapy has been under attack by manufacturers, providers, patients, and patient advocates. Critics argue that step therapy can delay access to more effective treatment and that such delays can result in poor outcomes. Step therapy may be poorly designed, may not be evidence-based, and may fail to address the specific needs of a patient (i.e., it may not be personalized). And when poorly implemented, step therapy may result in an onerous administrative burden.
Payers, on the other hand, defend the use of step therapy. Requiring the use of less-expensive treatments before more expensive options, they argue, can help to keep costs and premiums down, and for many, this may make treatment more (not less) accessible. Step therapy may be evidence-based and follow guidelines, a product’s labeled indications, and/or clinical trial inclusion and exclusion criteria.
Survival
Today’s step-therapy requirements, particularly those that have been in place for quite some time, have survived attacks from stakeholders (e.g., requests for medical exceptions, appeals, complaints, lawsuits, negative PR). In response to this pressure, some requirements have evolved. But you can’t see how step therapy has evolved by looking only at those in place today — those that have survived.
When Ryder surveyed spiral stairs in castles, his sample excluded castles that did not survive and those that were inaccessible for health and safety reasons due to their ruinous state, as well as many others not surveyed simply due to time and resource constraints. But survivorship bias may be at play. While a minority of the spiral stairs that survived and were surveyed were right-handed, it is possible that a majority of the spiral stairs that did not survive or were too ruinous to survey were left-handed. Newer technology (e.g., robots and drones) could, perhaps, be used to survey previously inaccessible stairs and help us get closer to the truth in the future. As said by Abraham Wald, a statistician tasked with an analysis to inform reinforcing World War II planes: “We do not know the distribution of hits on the planes that did not return.”
Looking back, we can see examples of step therapy evolving. Some payers have dropped steps through older, less-expensive, and less-effective therapies for conditions including multiple sclerosis, rheumatoid arthritis, psoriasis, psoriatic arthritis, and epilepsy. Some payers have reduced the number or duration of drugs first tried and failed prior to accessing newer, more targeted, and/or more expensive treatments (e.g., asthma, COPD, chronic migraine). Some payers are now providing earlier access to effective therapies (e.g., hepatitis C and ADHD). Including older policies in the analysis demonstrates that step therapy is responsive to environmental pressures.
Importantly, one should not conclude that all step-therapy protocols in place today are safe and effective and will survive the test of time. Some may be too new. And sufficient evidence may, for now, be lacking to pose a successful challenge against others. A disproportionate percentage of surviving castles with right-handed spiral stairs may have survived due to other military advantages (e.g., higher or thicker walls, greater human resources, equipment and supplies) despite the directional disadvantage of their spiral stairs. And some protocols may pose little to no conflict with certain patient populations, just as defenders of surviving castles with right-handed spiral stairs may disproportionately have been left-handed.
The future
Looking forward, step therapy will increasingly be driven by the explosion of genomic research and the rise of precision medicine, which targets the right treatments to the right patients at the right time. Genomic biomarkers are increasingly used to diagnose cancers and help select treatments including those for breast, non–small-cell lung, colorectal, and ovarian cancers, melanomas, and acute and chronic myeloid leukemias. Insights like these will accelerate as a result of advances in sequencing technologies, rapid expansion of genomic data, and newer analytic tools including artificial intelligence. The result: safer and more effective care.
Manufacturers could (but rarely do) bring to market a companion diagnostic to support personalized medicine. And manufacturers could go one step further and link their products to genetic (and one day epigenetic) information to support precision medicine. Perhaps their best defense against step therapy is a good offense.
Payers have a difficult time defending a step-therapy requirement that conflicts with evidence. Step-therapy requirements that conflict with precision medicine will likely not survive attacks unless the step is through a competing product with comparable safety and efficacy but with a stronger economic value proposition.
The future is clear. Step therapy will not go away, but the requirements will evolve and will increasingly follow our right-handed DNA as we ascend toward precision medicine.
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