The Ethics of Personalized Medicine: A Philosopher’s Perspective

March 1, 2014

March 1, 2014 – Below please find an article just published in Medscape Oncology News. Since in the age of personalized or individualized medicine, personalization or individualization is so personal or individual to each one of the readers of this blog, I thought it worthwhile to make available to you this philosophers view on the topic. Enjoy reading, and draw your own personal or individual conclusions. (May I add that I copied and pasted the article in its entirety from Medscape site, and are copyrights are entirely with Medscape. I left the list of references, which can be easily found at the site of the original article).

Start of Article

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It is a standard joke that when philosophers are asked to give a perspective on a topic, they first of all ask what it means and make no further progress. When it comes to personalized medicine, however, the question of meaning is very important insofar as our understanding of what is involved informs our understanding of the ethical issues. [1] This is critical, especially as the way issues are presented affects the expectations of patients. ‘Personalization’ suggests association with an individualist paradigm in ethics, although it may emerge that what is envisaged is more accurately described, at least in some cases, as stratification of the patient population into, for example, good or poor responders to a particular drug. Alternatively, patients may be divided into groups according to their disease type as more is learned about, for example, cancer subtypes. The prospects of increasing use of whole-genome sequencing (WGS), however, may make personalization a reality in a stronger sense.

The central idea of pharmacogenomics, that information about the variation in genetic make-up between individuals is relevant to prescription of drugs, introduced a specific sense to the concept of ‘personalization’ in which personalization became associated with a person’s genomic information. The ethical argument supporting this was the need to reduce the incidence of mortality and morbidity resulting from adverse drug responses. Personalized prescribing for a patient could be genetically informed, not only in relation to the choice of drug, but also in regards to dosage, thus minimizing the potential harm of inappropriate prescribing for a particular patient. Patients could be subdivided into those who could, and those who could not, tolerate a specific substance.

With the advent of WGS, the possibility of ‘tailoring’ medical advice and treatment to the individual throughout a lifetime becomes, at least, an in-principle possibility, although the term ‘tailoring’ was used by the UK Department of Health in 2003, before WGS was on the horizon. [2] The use of the tailoring metaphor gives a much stronger sense to personalization: all the multiple variations between individuals could be taken into account. In the clothing industry, there is a distinction between clothes tailored for the individual and those ready to wear for the mass market, and it might be tempting to think that this mirrors the distinction between personalized and blockbuster approaches to pharmaceuticals. However, within tailored clothing there is also a distinction between ‘bespoke’ and ‘made to measure’. Whereas ‘bespoke’ clothes are created without the use of a pre-existing pattern, ‘made to measure’ alters a standard-sized pattern to fit the customer. The move from genetic testing to WGS arguably suggests a move from ‘made to measure’ to ‘bespoke’. There is a caveat here, however, and that is that the word ‘bespoke’ comes from ‘bespeak’, which suggests that the individual is in control of the process. This may be where the analogy between personalized medicine and tailoring breaks down.

It is important not to overlook the fact that, although the ethical argument for personalized medicine was initially made to prevent adverse drug reactions (deeming it uncontroversial from that point of view), once a richer version of tailoring appears, attention also increasingly turns to benefits and to issues of equity in access. [3] The questions then are not only ‘how can we prevent harm to this person?’, but ‘how can we maximise the benefit?” and ‘how can we achieve justice in distribution?’ For example, suppose information emerges that, in relation to the prescription of a very expensive drug for cancer, some people may achieve a life extension of only a couple of weeks, while others may benefit with 2 years extra life. [4] It is not clear what criteria would be appropriate in such a situation. From one point of view, it might be argued that despite the variation in benefit, each person is entitled to receive the drug. From another, it might be argued that prescribing should be performed in order to maximize benefit.

There are also issues of international distribution to consider. Daar and Singer’s classic piece on pharmacogenomics and genetic ancestry argued eloquently against a situation in which the benefits of personalized medicine not only reinforced an individualistic ’boutique-style’ model of healthcare, but also operated to the disadvantage of less developed countries. [5] They argued a case for the possible benefits of ‘drug resuscitation’ in relation to products that had been taken off the market in the west, but which could also be beneficial in settings where the population had relevantly different genetic factors. [5]

Issues of equity impact strongly on public perceptions. When a new technology is introduced, there are always questions, not only relating to whether there are any new ethical issues, but also whether there are any public perception issues that might be challenging. This might be the case, for example, where personalization or stratification coincides with other ways of dividing up the population that might, historically, coincide with discrimination, such as racial or ethnic categories.

Some of the worries about personalized medicine arise in connection with its implementation. The rise of companies offering direct-to-consumer tests, for example, has led to criticisms over how the results might be interpreted, conveyed and misused. There are also concerns about what tests are offered, and the time at which tests may be offered. While it may be considered acceptable for an autonomous adult to decide to undertake genetic testing, there are different considerations relating to WGS at birth or even prenatally, for the purposes of personalized predictive medicine. [6] There is a view that prenatal genetic testing will become the standard of care. [7] However, over the past 15 years or so, the argument for a right not to know genetic information about oneself has been advanced, on the grounds that such knowledge may change one’s whole perception of one’s future life for the worse. [8] If widespread sequencing becomes the norm, to remain in ignorance may cease to be an option, and yet we should not necessarily think that knowledge here brings greater autonomy. The person ‘bespeaking’ the test is not identical with the one tested. There are also issues about the extent to which a genetic counseling model can be transferred to the new possibilities, or whether a consumer model is more appropriate.

For those who do want genetic testing and are prepared to pay for it, the price is falling, which may alleviate some of the concerns about access, but there are nevertheless concerns about control of the resulting data.

The promise of personalized medicine offers real exciting possibilities, and the language of personalization is becoming more than a rhetorical device: implementation is more complicated, partly because of the complexity of the mass of information emerging and partly because of concerns about implementation.

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End of Article


FDA Approves Companion Genetic Diagnostic Test for Erlotinib [Tarceva] in NSCLC

May 16, 2013

May 14, 2013 – The US Food and Drug Administration (FDA) today announced the approval of the cobas EGFR Mutation Test, a companion diagnostic for the cancer drug Erlotinib (Tarceva). This is the first FDA-approved companion diagnostic that can detect epidermal growth factor receptor (EGFR) gene mutations, which are present in approximately 10% of non-small cell lung cancers (NSCLCs).

The approval of this test comes at the same time as an expanded indication for Erlotinib (Tarceva). The FDA has also announced a labeling change for Erlotinib (Tarceva), and the drug is now indicated for first-line use in patients with metastasized NSCLC that tests positive for EGRF mutations. Until now, the official indication was second- or third-line use in advanced NSCLC.

“The approval of the cobas EGFR Mutation Test will allow physicians to identify non-small cell lung cancer patients who are candidates for receiving Erlotinib (Tarceva) as first-line therapy,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, in a statement. “Companion diagnostics play an important role in determining which therapies are the safest and most effective for a particular patient.”

The safety and effectiveness of the cobas EGFR Mutation Test was established with clinical data showing progression-free survival in NSCLC patients with specific types of EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) for 10.4 months when they received Erlotinib (Tarceva) treatment, compared with 5.4 months for those who received standard therapy.

In the United States, Erlotinib (Tarceva) is currently the only drug available for use in EGFR-positive NSCLC, although elsewhere in the world, another similar drug is widely used: Gefitinib (Iressa). A third drug in this class of EGFR tyrosine kinase inhibitors (TKIs), Afatinib (Tomtovok, by Boehringer Ingelheim), is close to approval, with an FDA decision expected in July 2013. Afatinib will also have its own companion diagnostic test (Therascreen EGFR PCR Kit, from Qiagen).

Using an EGFR TKI in the first-line treatment of EGFR-mutated NSCLC is recommended by several clinical guidelines, including the American Society of Clinical Oncology.

Patient outcomes are significantly better when compared with chemotherapy, so much so that it “would be a tragedy not to use” an EGFR inhibitor in EGFR-positive patients, according to one expert in the field, Edward Kim, MD, PhD, assistant professor of medicine and director of clinical operations at the University of Texas MD Anderson Cancer Center, in Houston. To not know whether the tumor is mutation-positive is not acceptable anymore, he added.

However, testing for mutations is not yet routine, and there are difficulties with obtaining lung cancer samples of sufficient size and quality, as well as disagreement over which is the best method for obtaining such samples, as recently reported by Medscape Medical News. In addition, there are issues with the costs of such testing, as outlined in a comment from a surgeon is response to that article.

The cobas EGFR Mutation Test is manufactured by the Roche Molecular Systems. Erlotinib is comarketed by California-based Genentech, a member of the Roche Group and OSI Pharmaceuticals.


Fatal Adverse Events with Pazopanib [Votrient], Sorafenib [Nexavar], and Sunitinib [Sutent]

February 12, 2012

February 12, 2012 – From an article published in Medscape Oncology News on February 9, 2012, we learn the following (article in full, all rights resting with Medscape Oncology News):

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February 9, 2012— New details on the risk for fatal adverse events associated with several targeted cancer drugs have come from a large meta-analysis of clinical trials, which was published online February 6 in the Journal of Clinical Oncology.

The drugs investigated were pazopanib (Votrient, GlaxoSmithKline), which is approved for use in renal cell carcinoma; sorafenib (Nexavar, Bayer & Onyx), which is approved for use in renal cell carcinoma and hepatocellular cancer; and sunitinib (Sutent, Pfizer), which is approved for use in hepatocellular cancer and gastrointestinal stromal tumors. All 3 products are vascular endothelial growth-factor (VEGF) receptor tyrosine kinase inhibitors.

The meta-analysis, which examined data on 4679 patients from 10 clinical trials, found that these 3 drugs were associated with fatal adverse events at a rate that was about twice that seen in the placebo groups. The crude incidence of fatal adverse events was 1.5% in patients taking these drugs, compared with 0.7% in patients in the placebo or control groups (relative risk [RR], 2.23; P = .023).

The most common cause of death was hemorrhage; the second most common was myocardial ischemia. Liver failure and congestive heart failure were also reported.

Senior author Toni Choueiri, MD, from the Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, said that clinicians need to be aware of the risks associated with these drugs.

“There is no doubt that for the average patient, these drugs have benefits,” Dr. Choueiri said in a statement. In fact, these drugs represent a major step forward in the treatment of several malignancies, and they have led to significant improvements in patient outcomes.

However, they are associated with a significant increase in the risk of developing fatal drug-related events, and “practitioners must be aware of the risks associated with their use and must provide rigorous monitoring to continue to improve patient outcomes,” the researchers note.

“While the absolute incidence of these fatal side effects is very small, the relative risks are higher,” Dr. Choueiri noted. In addition, the patients in this meta-analysis were participating in clinical trials and all had adequate organ function at study entry, so the overall incidence and risk for unreported fatal adverse events could be higher in common medical practice.


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