The price of life
The most expensive drugs currently being used in medicine tend to be for childhood rare diseases or cancer. The most costly drug on the market was Glybera, priced at 1 million euros. However, just one patient was treated, and the drug was pulled after 5 years because of lack of sales. In the cancer field, potentially curative immunotherapies are being used at costs ranging from 200 000 – 400 000 euros. Thus, the price of a human life appears to be between 400 000 and 1 million euros in developed societies.
Life was cheap
Looking at human history, and especially the 20th century, the value of human life has not been much. The list of mass killers is long. Topping many lists is Mao Zedong, who caused the death of up to 70 million of his compatriots. Joseph Stalin comes in as a good second with up to 60 million of his own killed. Hitler and his henchmen killed up to 30 million civilians.
Regimes that killed millions include the Nationalist government of China, the Imperial Japanese army, the private forces of Leopold II in Kongo, Ranavalona I of Madagascar (the only woman on the list, and quite an interesting story), the Khmer Rouge in Cambodia, and the serial holocausts in the Ottoman empire. Less well documented murderers include Genghis Khan and Timur Lenk, who probably killed tens of millions each. Then there are of course various wars and conquests, where tens of millions died. Thus, historically, the price of life has been minimal.
After reaching its highest mark in the mid 20th century, the self-destructive nature of humanity seems to have petered out. Ruanda, Burundi, Darfur, East Timor and Yugoslavia remind us that it can still happen, but in general less people have been purposefully slain in the Nuclear Age.
Value of life increases
In developed countries, the value of life and the individual has been increasing in the past 50 years. From a philosophical point of view, this could relate to increasing secularism. If there is only one life, and no afterlife or rebirth, life starts to seem more valuable. The random mass killers of the past - war, infant mortality, childbirth, pandemics, epidemics, tuberculosis, plague and smallpox - are no longer common. Thus, the general feeling of safety has increased, and premature death has become perceived as unfair.
A luxury product
Together with a strong increase in the general wealth of humanity, especially in developed nations, there have been more resources available for medical research. Historically, scientific medicine (as opposed to “natural” or spiritual healing) has basically been a luxury product, which becomes affordable only after more basic needs have been met. Food, shelter, family, war and religion have taken priority. In the last 50 years, apparently these basic needs have been met to such degree, that there has been money left over for science.
In Europe medicine made some progress in antiquity, and some of this knowledge was retained in the Middle East during the Common Era. The Middle Ages constituted big steps backwards in medicine. All diseases were punishments from God, mediated by imbalances in the “humors”: blood, yellow bile, black bile and phlegm. Beyond prayer, basically the only treatment was venesection, letting of blood from the vein.
Things started to slowly improve in the 18th century, when microbes, anatomy and physiology started to be understood. However, the speed of development accelerated dramatically after World War 2. Although development continues to be rapid, heretofore the new millennium has been characterized by a high degree of regulation and dramatic increases in the bureaucracy of clinical trials. Consequently, academic clinical research with new drugs has ended in most of the world, as only companies can afford to pay for trials. Even for companies, the cost of trials has skyrocketed, correlating with prominent increases in the price of drugs approved (Hemminki A).
Too expensive drugs
The new millennium has seen unfortunate cases of effective drugs not being used because of cost. An illustrative example is Glybera (lipogene tiparvovec). This gene therapy was well tolerated and quite effective in treating a hereditary deficiency of lipoprotein lipase. This rare but deadly disease affects about one in million children. Both rarity and the patient population complicate clinical studies.
Two small trials were nevertheless performed, resulting in eventual approval by the European Medicines Agency.
The initial company (AMT) went bankrupt while the regulators were prevaricating. A new company, UniQure, picked up the drug (and AMT’s debts), and took it to the market. The drug was priced at circa 1 million euros, and apparently, only one patient was treated outside of trials. Eventually, the company did not renew the marketing approval, due to lack of sales. In the 5 years the drug was available, an estimated 25-50 patients could have been treated in Europe, in a potentially curative manner. Therefore, it is clear that the drug was not being used because of the high price.
Thus, this suggests that the price of life is less than 1 million euros.
Affordable expensive drugs
How about some successful examples. Soliris is a monoclonal antibody effective is certain rare diseases. It is priced at 700 000 $/year. Most hyper-expensive drugs are recombinant proteins used for enzyme replacement treatment of hereditary enzyme deficiencies. Examples include Elaprase (500 000 $/year), Naglazyme (365 000 $/year) and Cinryze (350 000 $/year).
There are also some conventional-sounding approaches which have been priced quite highly, because their indication is for rare (“orphan”) diseases. Some examples include Folotyn (360 000 $/year), a variant of an old chemotherapeutic, and Acthar (200 000 $/year), a conventional hormonal product. The latter has been a subject of recent controversy due to its 100 000% price increase in a monopoly situation.
In the cancer field, the dogma used to be that new drugs can cost around 50 000€ per quality adjusted life year. Higher than that would frequently result in negative cost-benefit analysis in evaluations such as performed by UK National Institute for Health and Care Excellence NICE. Thus, one can interpret that the value of life used to be around 50 000€/ year.
The 50 000€ dogma has apparently changed in recent years, with the advent of cancer immunotherapy. Checkpoint inhibitors such as pembrolizumab, nivolumab, ipilimumab, etc, can cost upwards of 200 000€ per patient. CAR-T cell therapies Kymriah and Yescarta are priced between 300 000 – 400 000€. CAR-T is a treatment resulting in high cure rates, and in the US they have an interesting pay-for-performance pricing model, where the company returns the payment if there is no efficacy at one month. Probably the price of these drugs has something to do with the fact the only comparative treatment is bone marrow transplantation, which costs around half a million on average and is less effective and more toxic than CAR-T.
Curative drugs fetch a higher price
A common denominator for the most expensive cancer drugs is their curative potential, which apparently allows for higher pricing than with effective, but not curative treatments. Although one denominator of drug pricing is the cost of clinical trials (Hemminki A), and production costs obviously have nothing to do with price, it is clear that for-profit companies will charge what they can, according to the rules of the market economy. For-profit companies cannot determine humanitarian values, only society can.
Some but not all of these drugs mentioned above are available in most developed countries. Prices tend to be similar, although somewhat higher in the US. Since payers are prepared to pay up to 400 000€ for potentially curative drugs, but not up to 1 million euros (Glybera), the price of life is somewhere between these numbers.
Fortunately for patients, but unfortunately for payers, there will be many more expensive drugs in the near future. Moreover, in the cancer field, combination immunotherapy will increase the overall costs of care. If and when new drugs enter the market at prices between 400 000 – 1 million, the exact price of life can be determined more accurately.
Akseli Hemminki, MD, PhD, eMBA
Professor of Oncology
Hemminki A. Crossing the Valley of Death with Advanced Therapy. Published by Nomerta, Turku, Finland, 2015. Available at http://www.nomerta.net and several e-book stores globally