Evidence Underpinning Caris Molecular Intelligence’s Treatment Associations

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Caris Molecular Intelligence (CMI) uses comprehensive multiplatform molecular profiling technology to provide individualised cancer treatment recommendations. CMI has an extensive evidence review process to ensure that all technologies, services and treatment options are supported by strong clinical evidence. Ultimately, this means that the results of profiling provided to your doctor can guide well-informed, evidence-based decisions on your treatment plan.

Why molecular profiling?

Molecular profiling is particularly valuable for those who have run out of standard treatment options, for those with rare or aggressive cancer, or if there are multiple treatment options available for that type of cancer. A molecular profile reveals the unique characteristics of a person’s cancer at the molecular level, providing doctors with knowledge about which treatments are most likely to produce the best results, including treatments that may not have been previously considered. Molecular profiling will also help you avoid treatments that are ineffective, unnecessary, and potentially harmful.

How molecular profiling can be used to identify the most useful treatments

In order to identify clinically relevant and actionable targets for each person’s cancer, CMI uses a multiplatform approach to examine biomarkers from across the scope of molecular biology – including DNA, RNA and proteins – using, cutting-edge technology validated to the highest standards. CMI uses only clinically proven predictive biomarkers with a clinical sensitivity beyond 95% (the higher the sensitivity of a test, the greater the ability of the test to detect the biomarker).

96% of drug –biomarker associations that guide CMI’s treatment decisions are based on level 1 and level 2 evidence.1 These levels are based on the U.S. Preventive Services Task Force (USPSTF) approach to grading evidence, which is the most commonly used standard. Using this approach, level 1 evidence is obtained from at least one properly designed randomised controlled trial, and level 2 evidence is obtained from well-designed controlled trials without randomisation, well-designed cohort studies and well-designed case-control analytic studies.5

Table 1: USPSTF Evidence Codes5

IEvidence obtained from at least one properly designed randomised controlled trial.
II-1Evidence obtained from well-designed controlled trials without randomisation.
II-2Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one centre or research group.
II-3Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.
IIIOpinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.


The evidence review process at Caris

Caris Molecular Intelligence’s evidence review process consists of two stages.  Firstly, CMI’s evidence team continually reviews new relevant clinical literature on predictive biomarkers. Overseen by expert scientists, pathologists and clinicians, the evidence team grades and summarises all available evidence, both negative and supportive. Existing Caris treatment associations are also continually checked against new and emerging evidence.

Then, a dedicated and multidisciplinary team comprised of internal and external oncologists, research scientists, pathologists and clinicians (CMI’s evidence board) further discusses and reviews the compiled information. The evidence board, who generally meets every month, reaches consensus about the reviewed and graded evidence, and whether it should be incorporated into CMI’s services.

After these two stages of review, a number of further steps are systemically undertaken.  This includes senior management approval, test development and validation, development and testing of necessary software changes, seeking approval from the relevant authorities, and plan rollout.  The entire process – from review to implementation – typically takes two months or longer.

Over 120,000 relevant clinical publications were screened and graded to characterise the predictive value of biomarkers which developed CMI’s panel of tests.1,2 CMI’s evidence review process has also enabled the inclusion of treatment associations for more than 60 drugs into its services, based on the profile of over 80 biomarkers.1

Figure 1: Generating Molecular Intelligence – An Overview of the Caris Evidence Process1

The FOCUS study: an example of reviewed evidence

The FOCUS study is an example of the type of medical literature reviewed and graded by CMI’s evidence process. This was a study involving 1,628 patients with colorectal cancer who were profiled for several biomarkers. FOCUS demonstrated that colorectal cancer patients with high expression of the biomarker topoisomerase-1 (Topo1) had a significantly higher overall survival probability if they were treated with combination treatment (fluorouracil and irinotecan) compared with fluorouracil alone. Importantly, the difference in treatment outcome was not seen in those with a low expression of Topo1.3

From CMI’s evidence review process to your treating doctor

When your treating physician receives the CMI report, all of the results are supported by the relevant references from the peer-reviewed literature as determined by the evidence process. Your oncologist can also review in detail the biomarker testing that was conducted, and be linked directly to the clinical evidence supporting the drug–biomarker association.1

As a result of CMI’s exemplary evidence process that provides the basis for matching quality evidence with multiplatform test results, physicians are able to make well-informed, evidence-based decisions about which drugs are more likely to benefit an individual patient, and which drugs should be avoided.1



  1. Ussia G, Leonard R, Janssens J. Multi-platform tumour profiling delivers the highest clinical utility and improves patient outcomes in today’s routine clinical practice. Int J Surg Surgical Proced. 2016; 1:107. [PDF]
  2. Russell K, Shunyakov L, Dicke KA, et al. A practical approach to aid physician interpretation of clinically actionable predictive biomarker results in a multi-platform tumor profiling service. Front Pharmacol. 2014; 5:76. [Full text]
  3. Braun MS, Richman SD, Quirke P, et al. Predictive biomarkers of chemotherapy efficacy in colorectal cancer: Results from the UK MRC FOCUS trial. J Clin Oncol. 2008;26(16):2690-8. [Full text]
  4. Atkins D, Eccles M, Flottorp S, et al. Systems for grading the quality of evidence and the strength of recommendations I: Critical appraisal of existing approaches The GRADE Working Group. BMC Health Serv Res. 2004;4(1):38. [Full text]
  5. Woolf SH, DiGuiseppi CG, Atkins D, Kamerow DB. Developing evidence-based clinical practice guidelines: lessons learned by the US Preventive Services Task Force. Annu Rev Public Health. 1996;17:511-38. [Full text]
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