While undeniable strides in medical research over the past few decades have proven invaluable in the search for a cancer cure, there is no shortage of obstacles that remain to be addressed. Perhaps the most evident are complications in the biology of the disease itself: among these, problems pertaining to cell identification and treatment specificity. Equally problematic, however, are setbacks in research policy. Such setbacks include a biased drug development process and inefficient clinical trial system, both of which delay the transition from medical discovery to clinical application.
In large part, translational research is mediated by the pharmaceutical industry. One of the largest disincentives to cancer drug development— and a driving force behind negotiations on the Biologics Price Competition and Innovation Act of 2009— has been the development of cheaper derivative biosimilars. This act vaguely defines biosimilars as “‘highly similar’ to the reference product ‘notwithstanding minor differences in clinically active components’” . The research costs associated with developing reference biologics, or original molecules upon which these patented biosimilars are based, are significant and include large expenditures on production technology and clinical trials . While there has been some debate about the amount of time necessary for a drug company to receive a return on its original investments, PhRMA (Pharmaceutical Manufacturers Association) has controversially pushed 12 years as the “bare minimum” for market exclusivity, a standard currently supported by the International Intellectual Property Institute [2, 3].
When considering the competing motivations of the pharmaceutical industry and its clients, it is important to reconcile the interests of each stakeholder. This was the primary aim behind the Biologics Price Competition and Innovation Act. Because they monopolize the market, biologics remain some of the most expensive drugs available, rendering 12 years of patent exclusivity highly restrictive. On the other hand, current legislation permits competitors to run tests on the original product and to develop generic alternatives while its patent is still in effect. This allows “a generic product to be marketed virtually the moment the [original] patent expires” . The market, originally under-stocked and overpriced, quickly becomes saturated with derivative generics because of the lack of financial incentive to research novel drugs.
One temporary solution proposed for the initial cost problem has been governmental subsidy, granted directly to the pharmaceutical company or indirectly to patients. The former idea, while intended to lower prices and foster development of new bio-technologies, has been criticized for placing too much power in the hands of large bio-tech companies. There looms the possibility that companies might use the spare money to “tinker with” existing products, rather than investing it in the more costly task of developing new formulas . The latter idea, through the distribution of pharma coupons, tends to favor “commercially insured eligible patients”, yet excludes the uninsured or those with publicly funded health insurance plans . For different reasons, neither of these solutions arrives at the root of the problem.
Might there be a better way to defray development costs—and concurrently, lower pricing? The answer could lie in formal collaboration. While highly prolific, academic institutions do not always experience the practical application of their research. Drug companies, on the other hand, have the resources to disseminate facets of this research at large. Governmental support for pharmaceutical initiatives is tentative at best. Universities, however, tend to be attractive candidates for federal funding. Jose Carlos Gutierrez-Ramos—Head of the Immuno-Inflamation Center of Excellence for Drug Discovery—comments on his partnership with the Immune Disease Institute at Harvard University: “[we wish to] capitalize on their science and on our ability to develop drugs…in a way that is mutually beneficial—certainly for society but also for the principal investigator and the organization” . Admittedly, the motivations of each party may not always align. For instance, the desire of academics to publish their research may conflict with the industry’s wish to protect proprietary information for marketing purposes. Nonetheless, the benefits of an academic-industrial alliance generally outweigh its potential disadvantages, and these collaborations are making an impact on the global scale. In March 2011 Europe witnessed the launch of OncoTrack, a five year, $35.6 million project to evaluate and implement new techniques in the treatment of colon cancer .
The second, critical barrier between bench and bedside is the inefficiency of clinical trials, and their associated misconceptions. While trials are capable of granting patients the most scientifically advanced treatments available, they fail to attract more than 5% of adults diagnosed with cancer each year . One recent study at the Department of Radiation Oncology explored reasons for low clinical trial participation rates, revealing noteworthy trends amongst certain cohorts of the population . In this particular study, minority groups were 12% more likely to decline participation than non-minority groups. This finding is attributed to possible mistrust in the healthcare system, exacerbated by the lack of minority physicians who might help overcome said mistrust. Another surprising finding revealed that married patients were more likely to decline participation than single patients. Because consent forms for cancer clinical trials are notoriously lengthy (on the order of 50 pages) and explicit (listing in detail every potential side effect, in many cases including death), they are thought to elicit spouse dissuasion. This attitude might be symptomatic of a larger misunderstanding of the comparative benefits and disadvantages of clinical trial participation, making effective, intuitive liaisons between researchers and the general public all the more pressing.
The National Cancer Institute (NCI) has proven instrumental in facilitating clinical trial participation (one of its many services) but is not perfect by any means. A 2010 report by the Institute of Medicine outlines several suggestions for improvement . For one, the report recommends a tighter methodological uniformity amongst clinical trials, which would facilitate subsequent “comparative effectiveness studies” . These studies are designed to draft an informative hierarchy of the most efficient clinical treatments. Moreover, in order to ensure the broadest applicability of trial results (considering the inconsistent features of different cancers and the highly variable genetic makeup of distinct individuals), the NCI might expand patient advocacy programs to recruit subjects of diverse backgrounds, and principal investigators may reconsider eligibility restrictions when formulating clinical trial protocols.
Furthermore, the NCI is in the position to advocate better recognition (i.e. pay raises, more generous tenure considerations) of physicians working in clinical trials, and to support emerging physicians (i.e. grants, fellowships), thus encouraging sustained interest in medical research .
Finally, the NCI could more aggressively lobby for insurance coverage of non-experimental patient healthcare costs while they are enrolled in clinical trials . Currently, insurance companies widely believe that the expense of putting their clients through clinical trials outstrips that of pursuing traditional medical treatment. However, one 2001 study showed this to be a misconception. In this study, Dr. Thomas N. Chirikos and colleagues examined the hospital billing records for nearly 2,000 cancer patients participating in clinical trials and compared them to those of patients who received regular treatment. “When the researchers adjusted the data to isolate the effect of trial participation alone, the investigators found that in all but one case, there was no statistically significant difference in the costs of care for patients who were enrolled in trials compared to those who were not” .
Although particularly worrisome when dealing with serious diseases like cancer, the policy pitfalls that prevent effective research and application can be applied to any medical context. The first step in streamlining the research-healthcare pipeline is to raise awareness, and thereafter, to enact legislation that expedites the development pathway from research labs to hospitals— resulting in one that is efficient, yet still adheres to acceptable standards of ethics and scientific rigor.
- Loren R. New Law! The Biologics Price Competition and Innovation Act of 2009. Martindale [Internet]. 2010 Apr. Available from: http://www.martindale.com/health-care-law/article_Edwards-Angell-Palmer-Dodge-LLP_976250.htm
- Lehman B. The Pharmaceutical Industry and the Patent System. [Internet]. 2003 Dec. Available from: http://www.earth.columbia.edu/cgsd/documents/lehman.pdf
- Tumulty K, Scherer M. How Drug-Industry Lobbyists Won on Health-Care. Time [Internet]. 2009 Oct 22. Available from: http://www.time.com/time/politics/article/0,8599,1931595-2,00.html
- Holden C. Research on Contraception Still in the Doldrums. Science [Internet]. 2002 Jun 21; 296:5576. p. 2172-2173. Available at: http://www.sciencemag.org/content/296/5576/2172.full
- Wellsphere. Pharma Coupons: Enriching the Drug Companies. Wellsphere [Internet]. 2001 Jan 11. Available from: http://www.wellsphere.com/healthcare-industry-policy-article/pharma-coupons-enriching-the-drug-companies/1327876
- Hughes B. Pharma pursues novel models for academic collaboration. Nature [Internet]. 2008 Aug; 7. p. 631-632. Doi: 10.1038/nrd2648. Available from: http://www.nature.com/nrd/journal/v7/n8/full/nrd2648.html
- GenomeWeb. OncoTrack Consortium Launches $35.6M Colon Cancer Initiative. GenomeWeb [Internet]. 2011 Mar 11. Available at: http://www.genomeweb.com/oncotrack-consortium-launches-356m-colon-cancer-initiative
- American Association for Cancer Research. Cancer Policy Issue Briefs. ARC [Internet]. Available at: http://www.aacr.org/home/public–media/science-policy–government-affairs/cancer-policy-issue-briefs/cancer-research.aspx#D
- Marinucci M. Barriers to Participation in Cancer Clinical Trials: Improvement Recommendations for Missed Opportunities to Address Disparities. Jefferson Health Policy Capstone 5 [Internet]. 2009 Aug 4. Available at: http://aisr3.jefferson.edu:880/ess/echo/presentation/d5349536-a4d5-4c7e-bb05-7b3279450b99
- Institute of Medicine. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. IOM [Internet]. 2010 Apr 15. Available at: http://www.iom.edu/Reports/2010/A-National-Cancer-Clinical-Trials-System-for-the-21st-Century-Reinvigorating-the-NCI-Cooperative.aspx
- National Cancer Institute. Cancer Trials Appear Not to Drive Up Cost of Cancer Treatment. NCI [Internet]. 2003 Jan 27. Available at: http://www.cancer.gov/clinicaltrials/conducting/developments/notcostly0103
- Nelson R. NCI Cooperative Group Program in Need of an Overhaul. Medscape [Internet]. 2010 Apr 16. Available at: http://www.medscape.com/viewarticle/720386
- Varian, H. [photograph] 2008. Available at: http://www.flickr.com/photos/horiavarlan/4273968004/