Losing Voltage: When Good Ideas Get Left Behind

Why is it that the results of well-controlled studies often, if not always, find them difficult to replicate in the real world? That loss of efficacy is termed the voltage effect, as described by John List. Here is a good example involving a less expensive way to maintain healthy outcomes.

“Human incompetence, laziness, and wastefulness should not be underestimated—especially at scale!”

― John A. List, The Voltage Effect: How to Make Good Ideas Great and Great Ideas Scale [1]

Our story begins with a study published in the New England Journal of Medicine concerning the use of aspirin in treating the risk of forming blood clots after a severe fracture requiring operative repair. This is a known and, in some instances, lethal complication. While the mortality varies with the fracture site, in hip fractures, the presence of a deep vein thrombosis, the blood clot prevented by post-operative medications, increases the mortality from 0.3% to 7%.

The researchers tested the efficacy of aspirin at low doses compared to the current “gold-standard” guideline-recommended treatment with a low molecular weight heparin (LMWH), a more potent anticoagulant (blood thinner). Conducted over a 4-year interval across 21 Level I Trauma Centers in the US involving roughly 12,000 patients with fractures of their upper or lower extremity or pelvis requiring operative repair were randomly assigned to aspirin or LMWH. Patients were given these medications during hospitalization and for 21 days post-discharge. 

• 90.2% of the aspirin group completed care.
• 84.6% of the low-molecular-weight–heparin group completed care.

• Death occurred in 47 of 6101 patients (0.78%) in the aspirin group and 45 of 6110 patients (0.73%) in the low-molecular-weight–heparin group.
• While Aspirin was not superior to low-molecular-weight heparin, it was non-inferior to low-molecular-weight heparin in preventing death from any cause with no difference based upon the patient's age.
• While there were more pulmonary embolisms while taking aspirin over LMWH, the difference in mortality was insignificant.
• There were more deep venous thrombosis clots in areas other than the lungs in the aspirin group vs. LMWH.
• Complications from these medications, bleeding or wound problems, were essentially the same. Aspirin was equally as safe as LMWH.

The study’s limitations included a flexible period for post-discharge treatment and an open-label study design, both of which might have influenced outcomes. The researchers ended on a high note.

“Despite these limitations, our findings are clinically meaningful. Patients with orthopedic trauma strongly favor aspirin over low-molecular-weight heparin because of the lower costs and less burdensome administration of aspirin… The trial was performed at 21 sites with high follow-up (96.8%) and adherence (87.4%). An adjudication committee whose members were unaware of trial-group assignments reviewed all outcomes of death and pulmonary embolism, which further verified the reliability of our findings.”

18 Months Later and The Voltage Effect Takes Its Toll

“We and our colleagues thought that doctors and hospitals would immediately change their practice and switch to aspirin. This would improve health equity by providing a cheap treatment to people who can’t afford the more expensive one, and would improve quality of life by swapping painful injections for taking two aspirin tablets a day. Unfortunately, change is taking longer than we thought.”

Academic good intentions collide directly with real-world issues. They have a few points to make.

The study is from the Major Extremity Trauma Research Consortium (METRC), a group with $150 million in clinical grants for 34 studies in 22,000 patients, 72 national presentations, 57 publications, and “a pivotal role in integrating research results into Clinical Practice Guidelines (CPGs) and Appropriate Use Criteria (AUCs).” But eminence does not translate into action.

“When given a choice between two drugs that produce practically the same result in clinical trials, many doctors don’t follow the latest evidence and instead turn to hospital policy, habit, and preference as a basis for decision making. But they should use a health equity lens on a care choice as often as possible.”

That health equity primarily involves cost. LMWH runs anywhere from $70 to $300 weekly, while low-dose aspirin costs about $5 for six months. Some commercial insurance may cover the cost of LMWH, but that is not a guarantee. So, an equity argument in terms of cost serves the fiscal needs of these payors. Ironically, LMWH replaced the use of heparin at the turn of this century, and one of the main arguments after demonstrating “non-inferiority” was the cost savings. 

The researchers’ other lament is that doctors are not heeding their advice; instead, relying on hospital policy is ironic, too. Hospital policy is often based on guidelines, if for no reason other than CYA legal liability. And METRC studies have rightly been the foundation for different guidelines. However, health systems move slowly, and with today’s computerization, changing from one drug to another is not simply possible with a mouse click by a “provider.” Most care orders, especially in a field as organized as orthopedic surgery, are contained in “order sets,” pre-designed and approved care developed to enhance health equity by removing needless variations in care. Changing an order set requires a consensus among the providers and approval by various committees within the hospital. Then it must be incorporated into the digital workflow by the IT department. 

I must confess that I find the cost argument reframed as an issue of health equity a bit puzzling. Why would hospitals and physicians be more moved by equity of cost over equity of care?

In the end, the aspirin-versus-heparin saga is a perfect reminder that even when the science is solid, getting the medical community to switch gears is like trying to steer a cruise ship with a paddle. The researchers might have hoped for a swift revolution in treatment, but instead, they’re watching the same old drama unfold: a tug-of-war between innovation and inertia.

[1] You can find an excellent podcast about the topic here.

Sources: Aspirin after a broken bone: health equity in a $5 bottle, Stat

Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture NEJM DOI: 10.1056/NEJMoa2205973