REGULATORY METASTASIS: ALTERING THE REGULATORY AND PAYER LANDSCAPE TO CHANGE THE LIVES OF CANCER PATIENTS.

• Author: Camiel, Adam J.

1. INTRODUCTION

   It's a perplexing circumstance: a cancer drug can receive a different approval decision in the United States and Belgium, despite a pharmaceutical company submitting the same clinical datasets to the United States Food & Drug Administration (FDA) and the European Medicines Agency (EMA). (1) Furthermore, cancer patients in the European Union living in different countries may not have access to the same cancer drugs, even if the drugs they seek are approved by the EMA. (2) The FDA and the EMA could not differ more in their approaches to approving oncology therapeutics and interacting with insurance bodies. (3) Despite the fact that European socialized healthcare systems are lauded for their seemingly patient-centric and access-friendly models; the reality could not be farther from the truth for those patients suffering due to cancer. (4) The EMA is a decentralized agency that adopts a "centralized procedure," attempting to harmonize the national healthcare agencies of twenty-eight Member States. (5) Combined with that, each Member State has a different process of regulating approved drugs in socialized insurance systems, resulting in patients in the European Union receiving different access to care for identical illnesses based on their locations. (6)

   This Note explores the complex and exciting world of cancer care access: disparities between the United States and the European Union. (7) Part I begins by laying out the treatment paradigm for cancer and explains in chronological order how the treatment of cancer has advanced to its current stage. (8) Part II touches upon the history and mechanics of the FDA and the EMA, before explaining the structure of health insurance and reimbursement systems in the United States and European Union. (9) Part III lays out the differences in oncology drug approval timelines in the United States and Europe, as well as describes the current state of "politics in healthcare" and the effect it has on cancer patients. (10) Part IV delves into the problems with the European approach to healthcare and drug approvals, and why the model is not suited for cancer treatment in the modern era. (11) Finally, Part V concludes by juxtaposing the two agencies and making recommendations for reform in the EMA in order to increase access to oncology therapeutics throughout the European Union. (12)

2. HISTORY

   1. Understanding Cancer

      1. What is Cancer, and How Does it Present?

         Cancer itself is not a single disease or condition, but is the name given to a collection of diseases that stem from the body reproducing malformed cells. (13) All cancers are characterized by cells dividing and replicating uncontrollably, thereby affecting the functionality of the body's complex and interdependent systems. (14) Cancer can occur anywhere in the human body, from the scalps of women to the breasts of men. (15) In a normal cell life cycle old cells die and new cells take their place; for patients suffering from cancer this process does not occur and doctors see old cells survive or multiply when they should die. (16) Clusters of these cancer cells are known as tumors. (17)

         Tumors can be solid or liquid. (18) Solid tumors present as masses of benign or malignant tissue, usually obstructing key body cavities, or preventing normal organ function; liquid tumors present in the bloodstream, bone marrow, or other areas of the body where fluid readily flows and do not present as large masses of cells, but usually individual blood cells. (19) Both solid and liquid tumors can be either benign, meaning non-cancerous, or malignant, meaning cancerous. (20) Benign tumors, unless located in the brain, generally do not pose a risk to mortality as they do not spread to adjacent areas of the body, but conversely can grow to become large and still cause other health complications. (21) Malignant tumors, on the other hand, pose significant risks to a patient's mortality: they do not only spread uncontrollably, but pieces of them can break off from their primary location and travel around the body. (22) This process of spreading to additional areas of the body away from the primary cancer is called metastasis (23)

         Many patients suffering from metastatic cancers are terminal. (24) Interestingly, no matter where a cancer metastasizes, it retains the nomenclature of the primary cancer. (25) For instance, cancer that metastasizes from the breast to the lung would still be diagnosed as breast cancer, even if the patient were to die of lung-related complications. (26) In addition, the cellular makeup of metastatic cancer cells are extremely similar to that of the primary cancer, including the presence of certain chromosomal alterations which may or may not make the cancer more difficult to treat regardless of where it resides in the body. (27) Treating patients with metastatic cancer may result in the prolonging of life, but most patients that succumb to cancer die from metastatic cancer. (28)

         In terms of classifications of cancer cells, Carcinomas are most common, formed by epithelial cells which cover all surfaces of the body. (29) Sarcomas, also common, form in bones and soft tissues. (30) Leukemias appear in bone marrow and do not form solid tumors, instead presenting as large groups of abnormal white blood cells (known as "blasts" and liquid tumors). (31) Lymphomas, another liquid tumor, begin as white blood cells known as T or B cells, and amass in lymph nodes and vessels. (32) Rounding out common forms of cancer cells are melanomas and brain and spinal tumors, which form on pigmented tissues and nervous tissues, respectively. (33)

      2. Why is Cancer so Deadly?

         Cancer cells are programmed differently than normal cells. (34) Cancerous cells do not undergo apoptosis, also known as "cell death." (35) Seemingly most important, cancer cells also possess the ability to evade the body's immune system. (36) Cancer cells leverage the immune system and use the same bodily systems that normally prevent a runaway immune response to instead prevent the destruction of malignant cells. (37)

         At its core, cancer is simply a genetic disease, "causing changes to genes that control the way" cells operate throughout their life cycles. (38) Though cancerous mutations can be inherited from parents, these genetic mutations can also present because of a patient's lifestyle choices. (39) DNA can be damaged by continued exposure to certain elements which results in a change in the way cells behave. (40) Many risk factors are associated with damage to cells such as alcohol and tobacco abuse. (41) In addition, numerous risk factors are identified through epidemiology studies; where data scientists analyze groups of people with cancer against control groups of people without cancer. (42) The results of the studies normally point to a specific target population of people who suffer from cancer based on their innate characteristics. (43)

         Critical to remember when discussing cancer and mortality rates is that not all cancers kill immediately. (44) In fact, "more than 50% of people diagnosed with cancer live for more than five years"--a welcomed fact for patients who initially think cancer is a death sentence. (45) More importantly, cancer does not generally kill at an early stage, emphasizing the importance of earlier diagnoses. (46) Conversely, there is no one way cancer kills; cancer presents a number of problems for physicians because of the sheer number of ways it manifests itself combined with the numerous number of ways it can kill. (47)

      3. Treating Cancer: The Past, Present, and Future of Cancer Care

         The earliest evidence of a cancer diagnosis dates back to 1500 B.C. by the ancient Egyptians, who recorded that tumors were surgically removed, analogous to surgical treatment today. (48) Over human history, there have been many theories formulated as to how cancer forms. (49) Hippocrates, citing his Humorism theory, believed that an excess of black bile in any given organ site caused cancer. (50) The Humorism-based cancer theory held for more than 1,300 years. (51) From the seventeenth to nineteenth centuries, the lymph and blastema theories dominated the oncology landscape, contending that cancer was formed by the abnormal movement of fluid throughout the body and by small blastemas between pockets of tissue. (52) Other causation theories put forth by physicians that have since been disproven include that cancer is caused by trauma or by parasitic activity. (53)

         The breakthrough in understanding cancer occurred in the middle of the twentieth century after the discovery of helical DNA structure by Watson and Crick, who received a Nobel Prize for their groundbreaking work. (54) After learning how genes worked, scientists discovered that cancer could be caused by carcinogens such as chemicals, radiation, viruses, as well as through inherited genes. (55) Damaged DNA strands do not die, and thus cause issues in replication, resulting in cancerous cell growth. (56) Another push forward in understanding came in the 1970s, when two crucial families of genes were discovered that related to cancer: the oncogene and tumor suppressor genes. (57)

         Oncogenes cause cancer by stimulating abnormal cell growth. (58) Tumor suppressor genes, on the other hand, control cell division; when these genes malfunction, cells divide out of control--characterized as cancer. (59)

         The treatment of cancer has come a long ways since ancient human history when Egyptians crudely removed tumors from patients using primitive methods. (60) The development of anesthesia in 1846 allowed patients to have their tumors removed painlessly, but mortality rates were high. (61) Other developments contributing to cancer research included the widespread adoption of ultrasound technology, CT scanning, and MRIs; these advances in the twentieth century allowed physicians to pinpoint the location of cancerous growths without using invasive methods. (62) Surgical techniques and approaches...