III. Why is there no cure for cancer?
“It is now conceivable that our children’s children will know the term cancer only as a constellation of stars” — President Bill Clinton
The drug development pipeline that stretches from bench to the clinic begins with basic biomedical research. 85% of this research in the US is conducted using taxpayer money with drug companies spending only 1–3% of their revenues on basic research and 5–13% on clinical research. More recently, it has been suggested that greater collaboration between the public and private stakeholders of cancer research, namely the National Cancer Institute (NCI), the U.S. Food & Drug Administration (FDA) and pharma companies, would expedite the process of bringing novel cancer drugs into the market while cutting costs of conducting clinical trials.
This well-intentioned, neoliberal approach to improving outcomes for cancer patients is flawed to begin with for two main reasons — 1) a public-private sector collaboration on a basic need, i.e., healthcare, offers greater benefits to the private sector and 2) the privatization of academic biomedical research, a publicly funded enterprise, benefits only a few while corrupting the very framework of the scientific method.
Since the early 1980s, universities and institutes that enjoy a non-profit status, have become increasingly profit-seeking, as legislations allowed for patenting of “anything under the sun made by man.” The 90s saw a more subtle wave of privatization to boost translational research and public-private partnerships. This continued well into the 2000s, especially with FDA’s Critical Path Initiative launched in 2004.
Unfortunately, evidence shows that privatization has provided perverse incentives for researchers, and ultimately, created the current chaos that reigns in cancer research today. The current state of research shows an ailing system with spawning of predatory journals, transparency issues in established medical journals, sham conferences, plethora of reproducibility issues in basic research, corruption among scientists and abuse of public funds for personal gains. This reflects the “quantity over quality” approach where scientific trainees (graduate students & post-doctoral scholars) are often exploited in a tight budget climate. Not that more money had resulted in better research — when NIH’s budget doubled between 1997–2003, the growth was mainly observed in ancillary markets such as reagent companies, expansion of universities, and number of NIH contractors.
Scientists currently operate within a “publish or perish” system where journals increasingly pressure them to publish complete stories that start with basic discoveries and end with translational applications. This has led to an inflation of translational claims based on experiments with faulty preclinical models that focus on shrinking the primary tumor without much followup on overall survival (majority of cancer deaths result from metastasis and not primary tumors). A study found that 50% of new, unapproved oncology drugs written about in 2015 (right after American Society of Oncology conference) were described using superlatives such as “breakthrough”, “game changer”, “miracle”, “cure”, etc., and 14% of these had no clinical human data.
This gold rush to put out new drugs in the market has resulted in the increasing use of surrogate endpoints in clinical trials — 55% of drugs approved by FDA between 2009–14 were done based on surrogates. These endpoints, such as progression-free survival (PFS, the length of time during and after treatment that a patient lives without worsening conditions) and primary tumor growth, do not always correlate with overall survival (OS) and quality of life (QoL) that are more beneficiary for patients. In some cases, use of surrogate endpoints might actually result in greater harm in the long run, e.g. — bevacizumab was approved in combination with paclitaxel for metastatic HER2- breast cancer because it improved PFS by 5.9 months. However, followup showed that it had no benefit on OS or QoL and had greater toxicity. Between 2004–08, out of 36 cancer drugs approved using surrogates, 18 showed no OS benefit and 13 no known survival effects (17 of these are still routinely used). Additionally, it appears that the use of such endpoints benefit pharma companies by increasing sales as they use the “unmet clinical need” argument to bring such approved drugs for first line therapy that occupies a greater market share. This approval process is further aided by the expert opinions provided by physicians — an analysis of FDA’s Oncology Drug Advisory meetings between 2011–15 showed that most of the expert speakers received sizable industry payments. Interestingly, these payments do not need to be disclosed under current law (sunshine clause of Affordable Care Act) if they were made by companies without a drug in the market, making it easy for prospective companies to court physicians. If a lesson has been learned from the current opioid epidemic ravaging lives across the US, it is that doctors are often complicit in the exploitation of vulnerable populations.
