Personalized Medicine - page 8

Challenges of Implementing Personalized Medicine

The science is not yet ready for everyday use. Even once the science has been perfected, the successful implementation of personalized medicine is dependent upon several factors.

• First, there is a critical need to educate health professionals. The amount of genetics traditionally taught in medical schools is limited and typically focused on single-gene disorders and chromosome abnormalities, with little exposure of students to complex genetics.
• Second, the implementation of personalized medicine requires government support and regulatory oversight, as well as public vetting of ethical issues.
• Third, medical records systems must be structured to accept genetic data and integrate them with the patient's existing health record in a way that facilitates its use in clinical decision-making.

Image courtesy of: http://www.hhs.gov/myhealthcare/news/commissioned.html

• Fourth, challenges to evidence-based research into the effectiveness of personalized medicine include the need for large cohorts and longitudinal data collection to generate sufficient data in order to compute the treatment effect and gauge the potential costs and benefits.
• Fifth, there are also consent and privacy issues that come into play in large cohort studies. In addition, genetic studies of large cohorts require significant biobanking, genotyping and information technology infrastructure.

Personalized Medicine Depends on Biospecimen (tissue) Donation

Personalized medicine for cancer is in many cases still a vision for the future. For it to become a greater reality, cancerous and normal biospecimen samples will need to be:

• Donated by willing, informed individuals
• Collected, processed and stored in a standardized format
• Tested by both conventional pathology methods and genomic profiling
• Evaluated in the context of a patient's clinical medical history and their environmental exposure history.

Based on this information, a patient will be treated with therapies or approaches that target the cancer preferentially, while sparing normal tissue.

For more information about the importance of tissue donation from CISN go to:
https://cisncancer.org/research/how_cancer_is_studied/translational/biospecimen_issues.html

Standardization of Biospecimens is Crucial to Success

1. Patient Consent

Health professionals explain to the patient that their tissue donation is very important to accelerating progress in cancer research. If / when permission is given, the consent form is archived carefully and uniquely linked to the sample.

Advocates can play a role in this process by educating the public about the importance of tissue donation. This is an individual's choice and although the progress of personalized medicine depends on tissue collection, no pressure should be brought by either advocates and/or doctors to influence a person in their decision.

The consent document needs to be understandable to the person being approached with implications for future use and confidentiality/privacy clearly explained.

2. Sample collection

It is critically important to understand how to collect cancer biospecimens properly, so that the information obtained from analyses, using approaches such as genome-wide profiling, are correct and not artifacts of mishandling.

3. Obtain and Stabilize Sample

A biospecimen is removed from the patient, taking great care to keep the sample biologically viable. These steps need to be standardized across the Country so in research, samples can be compared against each other to determine normal values and in the clinic, so values reported out to patients are valid and can be reproduced wherever that patient goes for treatment.

4. Attach unique identifier

A unique identifier is associated with the biospecimen. Unique identifiers link the tissue sample with its relevant annotated records, so future results from studies using this sample can again be associated with the original patient donor. Confidentiality must be adhered to.

5. Store carefully

A biospecimen is carefully stored in a location that monitors temperature and conditions to properly support the integrity of the tissue.

6. Retrieve and re-store carefully

When needed for analysis, a biospecimen is carefully retrieved, and if any sample remains afterward, it is re-stored with care.

7. Best Practices

Examples of Large Personalized Medicine Programs

We have listed several large-scale personalized medicine programs below to demonstrate work in progress. As you read through them you learn that there is quite a variety of approaches, some more broad than others.

1. The Coreill Personalized Medicine Collaborative CPMCT is enrolling individuals in a research study to investigate the impact of personalized medicine on health outcomes.

	Over the next several years, study participants will receive personalized genetic results for their risks of complex diseases such as cancer, heart disease and diabetes. Participants will be asked to complete follow-up questionnaires to inform the medical and scientific community about the utility of using genome information in medical care. The CPMC is an evidence-based research study designed to determine which elements of personal genetic data are valuable in clinical decision-making and healthcare outcomes.
Image courtesy of CPMC: http://cpmc.coriell.org/

As of 2011, the CPMC are enrolling participants into wellness and cancer arms. Close partnerships with area hospitals are designed to catalyze physician engagement in personalized medicine.

2. The Personalized Medicine Coalition published the second edition of 'The Case for Personalized Medicine' in May 2009. This report details how personalized medicine plays an increasingly integral role in delivering high-quality, cost-effective healthcare and presents evidence that personalized medicine will continue to grow in importance as scientific breakthroughs are translated into a new generation of targeted therapeutics. For more about this coalition go to: http://www.ageofpersonalizedmedicine.org/index.asp

3. Wisconsin Genomics Initiative (WGI)

On October 10, 2008, Wisconsin Governor Jim Doyle announced the Wisconsin Genomics Initiative, which is a collaborative research effort among Marshfield Clinic, Medical College of Wisconsin, University of Wisconsin School of Medicine and Public Health, and University of Wisconsin-Milwaukee.

The vision of WGI is to be able to predict for individual patients in a clinical setting the risks of disease susceptibility and treatment response using the combined power of cutting-edge genetic, phenotypic, and environmental analyses, thereby making the
promise of personalized medicine a reality. (figure below)

The key elements of the WGI strategy are to:

1) Genotype up to 20,000 participants for 1,000,000 genetic markers

2) Validate selected target phenotypes and multiple clinical attributes from the Marshfield Clinic.

3) Integrate genetic, phenotypic, and environmental information databases and develop the search engines to use data efficiently for scientific discovery

4) Build predictive computational models using machine learning and super-computer capability, for the key equation, Genetic + (Environment and Clinical) = Phenotype.

5) WGI will then conduct initial predictive studies (diabetes, obesity, coronary artery disease, and atrial fibrillation) to test and improve the scientific platform, as well as a genome-wide association study (GWAS). For more information go to:
http://www.hhs.gov/myhealthcare/news/community.html

4. Partnership for Personalized Medicine (PPM)

PPM is a nonprofit initiative whose goal is the development, validation and clinical application of new molecular diagnostics designed to improve health outcomes and, importantly, reduce health care costs.

The Partnership for Personalized Medicine is led by Dr. Lee Hartwell, President and Director of the Fred Hutchinson Cancer Research Center and 2001 Nobel laureate; Dr. Jeffrey Trent, President and Scientific Director of the Translational Genomics Research Institute (TGen); and Dr. George Poste, Director of the Biodesign Institute at Arizona State University.