Physicians' Dilemma: Equivalent Efficacy, 40-Fold Price Gap – The Ethical and Economic Crossroads in AMD Treatment

This excerpt is selected from the book Saving Sight by Dr. A Lam, an ophthalmologist currently affiliated with Tufts University School of Medicine in the United States. The stories he recounts are neither exceptional nor rare; rather, they represent commonplace yet profoundly dilemmatic scenarios encountered in physicians’ daily practice. By “dilemma,” I refer to the critical reflection physicians must undertake: among various medications, therapeutic approaches, or surgical options, which yields the optimal outcome for the patient’s condition? Such considerations are not covered in medical school textbooks but instead stem from a physician’s professional integrity and moral conscience. — Christmas Reading Notes



I am an ophthalmologist, and years of clinical experience have allowed me to master some practical tips for medication use. Specifically, these involve three commonly used clinical drugs: Avastin (bevacizumab), Lucentis (ranibizumab), and Eylea (aflibercept). In ophthalmology, these three agents are indicated for the treatment of the leading cause of blindness in the elderly—neovascular (wet) age-related macular degeneration (AMD). If a doctor informs you or your parents that you are developing age-related macular degeneration, it means that pathological changes associated with aging, such as hardening and exudation, have occurred in the capillaries of your fundus. Clinically, you may experience declining visual acuity, difficulty recognizing faces of people approaching from opposite directions, inability to watch television, and even incapacity to drive safely.

No need to worry. As I mentioned, I have a proven approach to treating this condition. I can perform intravitreal injections using any one of the three medications I previously discussed, and your condition will improve. First, the leakage from the abnormal microvasculature will be resolved; subsequently, your vision will significantly improve, restoring your sight.

However, life is often not that simple. The issue does not lie with the treatment regimen, but rather with these three drugs. All three are widely recognized within the industry as the most effective medications for treating AMD. Yet, the greatest dilemma remains their price.It is simply unbelievable for both patients and physicians. Lucentis and Eylea are priced at $2,000 and $1,850 per treatment dose, respectively. What about Avastin? It costs only $50 per treatment dose—a 40-fold difference!

Despite the vast differences in the prices of these three medications, rest assured that they are all covered by medical insurance!Therefore, patients need not worry about medication costs and treatment duration, allowing physicians to select the optimal therapeutic regimens and medications. It appears that this is the current state of affairs.
Recent survey statistics from ophthalmologists indicate:

64.3% of ophthalmologists prefer Avastin as the first-line treatment. Approximately 35% of ophthalmologists choose Lucentis and Eylea, which are nearly 40 times more expensive, as their first-line treatments. Why?Intuitively, it seems that choosing the more expensive medication might yield better outcomes than the cheaper alternative, Avastin. In medical school, we were taught in our medical ethics courses that we should treat patients as we would treat our own mothers or ourselves—is that correct?These ethical dilemmas and moral considerations plague physicians every minute of their daily work. Not only on a daily basis, but also in the treatment choices for each patient, similar issues arise. Therefore, beyond ethics and morality, professional practice requires physicians to adopt a patient-centered approach, integrating ethical principles into their daily work. Specifically, this means providing patients with effective yet pragmatic treatment plans, rather than numbing one’s mind or relying on intuition when selecting medications and therapeutic regimens.

In fact, my reason tells me that these idealized thoughts are unworkable!All industry peers and published research data indicate that Avastin is currently the optimal treatment option. 。However, some doctors choose Lucentis and Eylea for clear and rational reasons. They feel that opting for the more expensive drugs offers greater assurance.Regardless of whether the therapeutic differences between drugs are statistically significant, it is a physician’s responsibility to ensure that treatment is foolproof. This is also part of the medical ethics education we receive in medical school.

What if we were to discuss this issue from a broader perspective of public health and the healthcare system? The scarcity and limited availability of medical resources are factual premises. From the standpoint of public health resources and health insurance funding, there is clearly a significant disparity and risk between a cost of $50 per treatment course and a cost 40 times higher.

I still vividly remember the scene in 2005 when the clinical trial results of Lucentis were made public. The ophthalmologists, who had previously appeared somewhat reserved, seemed to have received a much-needed boost; they had finally anticipated the market launch of the new drug Lucentis and believed it would fundamentally transform the clinical treatment landscape for age-related macular degeneration (AMD).

But when it was revealed that the pharmaceutical company had priced Lucentis at $2,000 per treatment dose and recommended monthly administrations, we calculated that the annual treatment cost per eye would reach as high as $24,000. This left all ophthalmologists stunned.

In fact, the clinical application of drugs did not develop in the direction expected by pharmaceutical companies, who anticipated reaping huge profits from the launch of Lucentis. However, ophthalmologists continued to treat patients with Avastin. Subsequently, the company developed another new drug, Eylea, based on the same mechanism. Clinical trials showed that its efficacy in treating wet AMD was nearly comparable to or even better than that of Lucentis.

Faced with reality, doctors are compelled to consider prescribing high-cost medications, driven by several mindsets or reasons.They believe that due to patients’ individual circumstances (such as comorbidities), those high-priced medications may offer better therapeutic outcomes. Meanwhile, the clinical dosing intervals for Lucentis, Avastin, and Eylea are every 4 weeks, 6 weeks, and 8 weeks, respectively. Thus, the treatment regimen for Eylea is more suitable for certain patients, as it reduces the number of administrations by half. Additionally, there is another clear yet important distinction: Avastin is typically not manufactured by pharmaceutical companies specifically for ophthalmic use but is instead used “off-label” in clinical practice. Therefore, pharmaceutical companies do not need to obtain separate FDA approval for this indication to use it in the treatment of age-related macular degeneration (AMD).

Of course, an unavoidable issue is that insurance companies have different incentive mechanisms for physicians who prescribe new and high-priced drugs. Generally speaking, physicians receive a 4% commission based on the drug price. To be fair, physicians who choose to prescribe the two new drugs, Lucentis and Eylea, do so also in consideration of their own financial interests (it is only human to be honest and accept the compensation one deserves for their labor). This raises a thorny question: from a pragmatic and treatment-cost perspective, if patients can achieve equivalent therapeutic outcomes, is it more appropriate or justified to opt for the higher-priced medications?

In 2014, according to projections by the U.S. Centers for Medicare & Medicaid Services (which is funded by U.S. taxpayers),Over the next decade, if Avastin were chosen to treat patients with wet age-related macular degeneration (AMD), this single change alone would save $18 billion in federal Medicare expenditures. The resulting savings of $1,950 per treatment course (the cost difference between Lucentis and Avastin) could cover the full cost of vaccinating one child or help uninsured low-income individuals access better, more meaningful medical care.

At this point, I began to gradually understand that physicians should reflect on their professional ethics: how to spend every dollar of health insurance funds in a better and more meaningful way.The scarcity of medical resources in the United States and the year-on-year increase in health insurance costs have become nearly unmanageable. Physicians bear some responsibility for this situation. Therefore, it is essential to reflect on and uphold professional medical ethics from the perspectives of patient welfare and social responsibility by selecting the most cost-effective treatment plans for patients.

Certainly, some physicians and patients may even worry that they have lost the freedom to choose their treatment options. I believe the rationale should be as follows:"If we fail to consider public health resources and the medical service system from a societal perspective, and if we neglect the imperative to control healthcare costs, the day when we truly lose the freedom to choose the best medical care may not be far off."By then, everyone will have lost the freedom to choose—what remains of healthcare services will be inferior and last-resort treatment options. This is because the nation’s entire healthcare delivery and public health system is on the verge of bankruptcy!
Back to Reality

Typically, I discuss three different medication options with my patients, informing them of their disease status, the price of each drug, expected efficacy, and other relevant details.I would also honestly tell patients that if I or my mother had the same AMD, I would choose Avastin.Of course, I also recommend that some patients choose Eylea or Lucentis. This is because I anticipate that these patients have comorbidities. However, in the vast majority of cases, I would choose Avastin. As such, after careful consideration, my patients also choose or agree to use Avastin. I do not dictate their medication choices; rather, I perceive that patients make this prudent decision by weighing public welfare against their own medical needs, thereby consciously fulfilling their social obligations.

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