Diagnostic Testing: A New Field for Market Research (Part I)

By Rishard Salie, Ph.D., Research Manager

Companion diagnostics and the shift to personalized medicine

Over the last decade, the idea of personalized medicine, disease therapy tailored to the individual, has been realized to some extent in fields such as oncology, cardiology and communicable disease. How does the physician determine how to provide the correct drug, to the appropriate patient, at the proper dose? Personalized medicine depends on having accurate diagnostic tests that can identify patients who benefit most from therapies. New diagnostic tools are emerging as a major offshoot of the personalized medicine revolution, and they will be of paramount importance in the screening and diagnosis of patients and in optimizing therapy on a per-patient basis. Companion diagnostics are biomarker tests designed to assess if the patient is a good candidate for a specific type of therapy. They will help physicians make treatment decisions and increase patient quality of life by ensuring that only drugs with a high chance of working on a specific patient are prescribed. (Figure 1).


These tests also decrease overall treatment expenses by reducing costs associated with the treatment of patients and the management of side effects in patients who aren’t going to benefit from the treatment.

Companion diagnostics have the potential to incite large-scale changes in how patients are diagnosed, classified and treated. Integration of these new tests into the current treatment paradigm will raise many questions with respect to drug development and the practice of clinical medicine. The impact of companion diagnostics on the pharmaceutical market research landscape also needs to be assessed. As in any field, new developments and progress present a wealth of opportunities to those willing to embrace them, but in order to successfully adapt, market researchers need to be aware of the key drivers of change. New stakeholders and target groups must be carefully considered and integrated into our current research approaches. To address these issues, it’s important that we understand what companion diagnostics are, how they are developed and who the key players in this market will be.

Biomarkers: A historical perspective

The official National Institutes of Health definition of a biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” Biomarkers can be metabolic products, proteins, DNA, RNA, cell counts, sugars or enzymatic activities. They are anything that can be used to provide information that guides the physician’s therapeutic decisions. One of the earliest identified biomarkers is glucose in diabetic patients. For centuries, physicians were able to determine whether patients had diabetes by tasting their urine. If the urine was sweet, due to incomplete reabsorption of glucose by the kidney (glycosuria), the patient could be confirmed as diabetic. This remained one of the standard diagnostic tests for diabetes until the 20th century. In the 1960s, urine strips were developed that could define the presence or absence of glucose in the urine. Different brands of strips used different chemical reactions to assess the glucose level in the urine, which could be observed by a color change on the test strip. Later, strips for testing glucose levels in the blood were introduced, providing an accurate, real-time measure of blood sugar levels. By 1969, the first portable glucose meter was created by Ames Diagnostics. Electronic blood glucose meters do not measure glucose directly, but calculate the activity of enzymes that metabolize glucose. The hemoglobin A1c test, introduced in the 1970s, tracks glucose changes over the life span of the cell by measuring the amount of a specific type of hemoglobin present in blood.

These different tests all take advantage of diverse biomarkers to examine the same parameter – blood sugar level. Generally, multiple biomarkers can be assayed by different methods for any given disease parameter, but the biomarker must first be validated (proven to measure what it’s supposed to). Biomarkers have also been utilized in the determination of nondisease events, such as conception. Pregnancy tests detect the presence of the hormone human chorionic gonadotropin (hCG), a molecule secreted shortly after fertilization. An antibody specific to hCG binds to it in a urine sample from an absorbent swab, triggering a color change in an indicator present in a line on the display of a home pregnancy test. Tests commonly run at medical checkups are often based on biomarkers; kidney function is routinely assessed by measuring serum creatinine levels and creatinine clearance, while liver function is measured by testing for hepatic enzymes. To confirm a heart attack diagnosis, physicians measure levels of troponin, a molecule released into the blood by damaged cardiac muscle. While biomarkers have been used extensively in the past to diagnose disease, there has been relatively little success using them to fine-tune therapy until recently.

Rise of the companion diagnostic

In recent decades, knowledge regarding the biochemical pathways underlying diseases such as cancer, HIV and congenital disorders has increased tremendously, and studies of the human genome have revealed molecular causes for some of these. Even if the root cause has yet to be found, it is clear that some ailments, particularly cancers, can often be associated with a specific molecular signature. In recent years, there has been increasing interest in developing biomarkers for disease screening and detection. Classification of diseases at the molecular level, and the possibility of selecting ideal patients using biomarkers, has moved forward significantly in the last decade, but is still in its infancy. Numerous challenges will need to be overcome before biomarker use becomes a standard part of the therapeutic process.

The majority of biomarker candidates never move past the discovery phase, and thoroughly validated biomarkers that are used to guide clinical decisions are rare. The costs and associated financial risks of validating biomarkers, then developing accurate tests for them, have historically made biomarker development unattractive to pharmaceutical companies. Diagnostic tests created with a specific drug in mind could become obsolete if the drug fails to gain regulatory approval or if the treatment guidelines are revised. Furthermore, the time required to develop a companion diagnostic test has often been underestimated, resulting in diagnostic tests emerging after a drug has already been introduced to market. Once a drug is approved, pharmaceutical companies have little incentive to invest in biomarkers to guide treatment decisions, as this would likely restrict the population of patients treated, reducing overall sales. However, with the experiences of the last decades and the growing push toward personalized medicine, many companies have since reconsidered this stance. Physicians and well-informed patients are demanding more effective drugs, and the current state of global health care systems has created an enormous pressure for pharmaceutical companies to bring new drugs to market, with increased safety and efficacy, at lower cost and faster than ever before. Companion diagnostics will be a key factor in bringing these new drugs to market, as they have the potential to optimize clinical trial results by preselecting a study population most likely to respond well to the experimental therapy.

Strong therapeutic effects in a subset of patients will be much less likely to be diluted by trial patients who are not benefiting. This should make clinical trials less costly, reduce the failure rate and allow for the results to be interpreted more clearly. The development of an accurate biomarker assay offers pharmaceutical companies the tantalizing possibility of resurrecting promising drugs that were abandoned in development because only a subpopulation of patients benefited from them. These drugs would only be approved for patients who test positive for the biomarker, resulting in lower overall amounts of drug sold, but with higher efficacy and safety, meaning that a higher price can be achieved and more products are likely to be approved.

Companion diagnostic development

Like drug development, biomarker development is a multistage process with many challenges that must be overcome to make meaningful progress in the field. Until recently, diagnostic tests have been developed separately from the drug they are used with, often in phase II or III, resulting in an asynchronous release of the drug and the test. Recently, more companies have been developing both the drug and diagnostic together, and incorporating testing into their clinical trials, to define patient populations who might experience superior efficacy and screen out those who might exhibit toxicity.

Despite a few spectacular successes, the number of companion diagnostic tests used in drug development or clinical practice is very small. In an attempt to remedy this, the diagnostic development process is being streamlined to make it faster and more efficient (Figure 2).


International public–private partnerships are being formed to generate biomarker candidates and share data regarding methods and validation. These collaborations should decrease the cost of biomarker development and reduce the associated risks. Greater emphasis is also being placed on developing biomarkers for drugs already in use and might in the future be used to bring drugs to market that were only effective in a subset of tested patients.

The allure of companion diagnostics is clear, as are some of the barriers they will face. Stakeholder roles in successful implementation and marketing of these products must be considered, as does the question of which fields hold the highest potential for companion diagnostics and how they will impact the pharmaceutical market research landscape. The second part of this article, which will appear in the March edition of Pipeline, will examine these topics in more detail, and explore some of the opportunities, issues and open questions that market researchers will face in the coming years.