Finasteride Approval Evidence of a Clinical Research Problem in U.S.
July 11, 2019 - Michael was a 27-year-old with a happy life in New York City and a bright future as a book editor in front of him. That all changed after taking a seemingly harmless prescription drug known by the brand name Propecia.
Propecia, also known in its generic form as finasteride, is a prescription medication he took under a doctor’s supervision for male-pattern hair loss (MPHL). Prescribed for cosmetic reasons to men all over the country, saving them from embarrassing hair loss, his doctor presented it to him as harmless and relatively safe. So, for a young adult in the prime of his life who wanted to simply look his best, Michael did not have any major concern with taking it. The benefits far outweighed any risks. He trusted the medicine, his healthcare provider’s opinion and the fact that finasteride was approved by the U.S. Food and Drug Administration (FDA).
Well, little did Michael know there was a flaw in the decision-making process that affects him, and likely millions of others in the U.S., every time a healthcare provider presents a patient with the option to take, or to pass, on any medication.
In short, sometimes the research used to justify the safe and effective use of a medication may not be as strong as it should be prior to FDA approval.
Approved in 1992, finasteride was initially released in the U.S. to treat enlarged prostates — a condition known as benign prostatic hypertrophy, or BPH, which is common in older men, especially as they age. According to documentation on the FDA’s website, finasteride was approved despite drug-related adverse drug “experiences” (commonly referred to as “side effects” outside of the medical world) that were observed in clinical trials. These included impotence, decreased libido and decreased volume of ejaculate.
By 1997 the drug manufacturer, Merck, was successful in another finasteride drug approval, a common practice as drugs may be approved for one indication before gaining approval for another when the manufacturer determines, through research, that the drug could be beneficial in other ways.
This time the FDA decided to approve Merck’s request to market the drug for the treatment of MPHL, or androgenetic alopecia, in “MEN ONLY.” With the approval to market finasteride as a treatment for this very common condition, Merck saw its drug sales go in an entirely new direction. Younger men were added to the customer base, providing a platform for a relatively consistent increase in the number of finasteride prescriptions. Sales went from 3 million in 2006 to over 10 million by 2016, according to pharmacy data on ClinCalc.com.
However, yet again, there was concern about the drug based on what was observed in the clinical trials leading up to the 1997 FDA approval.
In fact, within one section of the approval documentation related to finasteride’s use for treating MPHL, the FDA noted that Merck would be required to conduct some form of post-marketing research on the drug. This basically means that while the FDA was generally comfortable with approving finasteride as “safe and effective” (the standard for every drug approval) for MPHL, there were still safety concerns that the agency believed Merck should research after the drug was on the market and being prescribed to men all over America. (Note: the specifics of finasteride’s post-marketing research commitment for this indication are redacted from the documentation on the FDA’s website.)
In examining the research findings that led to the approval of finasteride for the treatment of MPHL, one can suspect what may have given the FDA cause for concern.
One of the studies used to present data to justify the approval for this new indication showed that the vast majority of the slightly over 900 subjects were Caucasian males (785 to be exact), despite prior research evidence showing clinical and biochemical differences in androgen action between normal healthy individuals from different ethnic backgrounds. Researchers also noted a placebo effect, particularly a “substantial” placebo effect, in the investigators’ subjective assessments of whether finasteride made a positive difference in MPHL compared to the photographic assessments designed to show improvement, or lack thereof, in balding. The research additionally revealed a higher incidence of breast-related adverse drug events, like breast enlargement and breast tenderness, and even an acknowledgement that it was unknown if there were any long-term effects of finasteride in younger men with regard to male fertility and prostate neoplasia (prostate pre-cancer). Data also showed that there were sexual-related adverse drug experiences reported by subjects. However, the medical review of Merck’s submitted data results stated those experiences resolved, or improved.
Michael vividly remembers experiencing a sudden decline in his health after taking finasteride for approximately one week in late 2010. He proceeded to see numerous doctors and spend thousands of dollars on various treatments. However, his newfound health problems were destructive enough that they eventually forced him to end his career as a book editor and give up his life in New York City.
Now 35, he lives with a long list of medical issues and diagnoses. He battles a cognitive impairment that affects his memory, comprehension, attention, and visual-spatial abilities, among other areas. This impairment has made him not only unable to work as a book editor but also to work in any significant capacity at all. In fact, in a 2018 neuropsychological report, his doctor writes that he now lacks the cognitive capacity to hold even a low-skilled job, such as assembly-line work. His side effects further include chronic dizziness/lightheadedness, fatigue, inability to build muscle, reoccurring prostatitis, urinary frequency/urgency, low libido, slow recovery from injuries, inadequate blood flow in the capillaries in his toes, and profuse localized sweating. With issues this numerous, he’s normally homebound, unable to live the quality of life typical of a man his age. Not surprisingly, he deals with depression and anxiety.
Since he’s unable to work and financially support himself, he relies on his mother, with whom he now lives in a small New England city. It’s a humbling existence, but he does his best to stay uplifted and encouraged. He uses the Twitter handle @MeTooPropecia to bring attention to what Propecia can do, and has done, to men all over the world. The logic? If one person can be convinced not to take a chance with finasteride, then that’s another life saved.
However, despite Michael’s experience and the experiences of people like him, proving that any medicine has harmed a person is a very complicated undertaking, as doing so involves science and medicine but ultimately hinges on clinical opinion. So, even though multiple doctors have pointed to finasteride as the culprit of Michael’s health issues, this opinion has not been embraced by everyone, and the drug remains on the market today.
The approval of medications based on clinical research from small sample sizes that are not diversely represented and show signs of safety concern before approval is part of the FDA’s long and complicated history. Ultimately, every person in America is affected by the FDA’s work, and the agency’s job becomes even tougher when drugs are already on the market. Once available at a local pharmacy, certain drugs that presented with safety concerns during the clinical trial phase will be taken by the general public. Then, unlike the ‘round-the-clock monitoring of every subject during a clinical trial, patients like Michael are not closely followed to understand every aspect of a drug’s effect on their body.
So, in the case of finasteride, what would have happened if things were done differently?
Is it fair to say that Michael should have extensively researched the drug by reading not only the drug label but also the countless pages of documentation between the FDA and Merck related to finasteride’s approval? Would that have changed the outcome? And what about the issues he and others experience that may not have been listed on the label at the time they took the drug? Should every person be expected to develop a deep scientific understanding of a drug’s pharmaceutical effect on the human body in order to make their own determination on whether that drug is safe? That sounds neither fair nor reasonably feasible.
And what about Michael’s healthcare provider? Should he have been more cautious by refusing to prescribe finasteride to any of his patients without knowing for sure that it would never cause any side effects — permanent or otherwise? That does not sound logical either. How can we point the finger solely at healthcare providers when they are not responsible for the drug’s manufacturing, the drug’s regulation and the clinical research that declared finasteride as safe and effective?
So, what about the drug manufacturer?
If Merck decided not to pursue FDA drug approval based on the clinical trial results back in the ’90s, Michael and many other men would never have been harmed. That’s a fair conclusion, in theory, and in such a scenario there would be no such thing as “post-finasteride syndrome,” and nonprofits like the Post-Finasteride Syndrome Foundation would never have formed. However, is it really fair to say that Merck should have taken this action if it followed the rules and standards of human-subject research while pursuing its position as a global pharmaceutical market leader in a very competitive industry?
And what of the FDA?
If the agency had decided not to approve finasteride the first time, many men, including Michael, would have avoided the side effects. However, is it fair to say that the FDA acted outside of its governmental authority at the time to approve such a medication?
The answers are systemic and complicated, but the approval of a medication like finasteride reveals that we need to look much closer in our society at the entire lifecycle of a drug, from the moment it is researched to the moment it is sold to the public. Sure, doing so may not be easy, and just looking is not enough. But maybe we should start with raising the bar on the standards of clinical research.
Let’s ensure we know exactly who should take a drug and who should not. Before a drug is ever sold to the public, let’s invest in long-term research and dig deeper to understand every side effect that is reported in the clinical research phase. Let’s make sure we do not allow the approval of medications that help most people while simply accepting the fact that the same medications could injure or permanently disable others.
The lives of people like Michael depend on it.
(This article has also been published on Medium.)
Safest Drug is a 501(c)(3) non-profit on a mission to implement solutions that help to prevent and alleviate medication-related illness, disability and death. We plan to do this as consumer-focused advocates that lead education, community engagement, policy and research initiatives to better protect consumers, promote the voice of consumers' medication safety experiences and broaden the understanding of what it means to be medicated in America.