The Red Tape Awareness Ribbon

               Siddhartha Mukherjee’s Emperor of All Maladies is a biography of a malicious stalker of mankind which, throughout history, stalks men, women, and children without distinction for age, class, or wealth.  Mukherjee joins his fearsome biography of cancer with stories of victims, survivors, researchers and physicians who determinedly claw from the specter of cancer, the secrets necessary to banish its malevolence. 

            In over five hundred pages Mukherjee examines early attempts to treat cancer through mysticism, crude surgery, and inexpert experimentation which grew to include large government and privately funded crusades to end cancer by experimentation and research.  Understanding of the disease progressed from the balance of humors and fluids to cellular mutations and therapies to arrest malicious cellular alterations. Mukherjee describes the quest to solve cancer as driven by patient’s desire to survive the disease and the determination of researchers, scientists, and doctors to make that desire a reality.

            Mukherjee chronicles the passion of those combating cancer, particularly those who seek to preserve the lives of children.  Breaking new ground meant going beyond the expected and safe modalities of treatment to push forward toward new treatments.  Researcher and doctor Min Chiu Li, in the mid 1950s, linked the use of antifolates used to arrest bleeding from aggressive leukemia to reducing blood loss from choriocarcinomas.  Li started antifolates in a young woman rapidly dying from blood loss due to ruptures of tumors in her lungs.  So successful was the treatment that the patient appeared to be cured as her tumor shrunk to undetectable levels.  Common understanding of cancer treatments declared the patient cured but Li, through persistent observation, noted the minute yet continued presence of a cancer ‘marker’ hormone in the patient’s blood.  Li, contrary to established protocols, determined the cancer, although unobservable, still was extant in the patient’s body.  He continued to administer additional dosages of the drug until the hormone level reached zero. 

The National Cancer Institute, despite Li’s apparent success in curing the patient, accused Li of “experimenting on people” and fired him.  Emil Freireich, a fellow researcher noted, “Li was accused of experimenting on people, but of course all of us were experimenting…we were all experimenters. To not experiment would mean to follow the old rules-to do absolutely nothing.” Muckherjee reveals that decades later, clinical trials would prove Li’s assertion that total eradication of the disease required treatment until the cancer ‘marker’ was totally eliminated.  But, as Muckherjee would observe, “[I]n 1960, oncology was not yet ready for this proposal”.

            Because cancer is so indiscriminate regarding the victims it afflicts and, because in most cases, the discovery of the disease has few, if any precursor symptom’s, it is much as Mucherjee describes, an entity who arbitrarily seizes upon its ‘prey’.  Researchers and clinicians are often left with hope rather than certainty as they attempt to heal their patients.  The fear and anxiety of cancer victims drives clinicians often to desperation and spurs innovation.   However, often the passion of innovation is, as in Li’s case, stymied by bureaucratic systems slow to adapt to new technologies and alternative therapies and treatments.

            The extensive delay in the drug approval process conducted by the Food and Drug Administration (FDA) is a major factor hindering the introduction of new drugs for the treatment of many diseases including cancer.  For example, the FDA, in the past four years, increased the fees it charges drug companies for generic drug approval in order to speed review.  The change in fees netted the agency nearly $1 billion dollars in revenue.  Regardless, the time to process an application has risen from 30 months in 2011 to 48 months in 2014. David Gaugh, Senior Vice President of the Generic Pharmaceutical Association observes, “These delays contribute significantly to rising health care costs and impact access to pharmaceuticals for millions of patients.”[1]

            Delay in regulatory approval by the FDA is but one factor, the cost to bring one product to market is often staggering.  While the cost of bringing a product to market is impacted by many variables, the approval process can cost more than $1 billion dollars.  This includes $50-840 million to bring treatments through basic drug development trials and between $50-970 million to complete the various phases of clinical trials.[2]  Cost and delay significantly limit the ability of researchers to both bring new treatments to market and increase access to proven drug treatments through the production of less expensive generic alternatives.

            Another factor in adding to the cost and time required to introduce a new treatment is the seemingly needless duplication involving the necessity of obtaining approval by both American and European regulatory agencies.  As mentioned before, the FDA depends upon its Center for Drug Evaluation and Research (CDER) to supervise manufacturer’s clinical trials before a drug may be introduced to the public.  This process may take several years.  In Europe, there are two paths which approval for medicines may be obtained through the European Medicines Evaluation Agency (EMEA). A “centralized system” which scrutinizes drugs for AIDS, neuro-degenerative conditions, and diabetes. The ”decentralized system” reviews all other types of drugs.  A drug may be approved by either process and receive a marketing authorization but a manufacturer must then apply to each country before selling its drug.  There is debate about whether the FDA or EMEA process is quicker.  What is certain is that a drug may be approved by one country’s regulatory body and not another.[3]  Additionally, the clinical trial protocols of one national agency are not accepted by the other requiring the expense and delay of dual testing.  A single international standard testing regimen needs to be established to both reduce the expense and delay of introducing treatments to the market. 

            If researchers and clinicians are to fulfill the passion of defeating Muckerjee’s animated ‘cancer’ the drug testing and approval process must be streamlined.  Patients, as in the case of Doctor Li, are deprived of new treatments because bureaucratic malaise, needless duplication in approval processes, and an inability to ‘keep up’ with lightning fast developments in technology have delayed and acted as a deterrent to the development of new drugs aimed at ending the terror of the disease which stalks among us.

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[1] http://triblive.com/business/headlines/10201573-74/generic-drug-drugs

[2] http://www.brightfocus.org/clinical-trials/how-clinical-trials-work/fda-approval-process

[3] http://www.medicalnewstoday.com/articles/228776.php