Trend towards advanced specialty healthcare accelerating in the Middle East

Industry leaders at Arab Health 2014 to review delivery of healthcare services in the Middle East
Dubai, UAE: Although science and technology will undoubtedly play a significant role in enhancing
and enabling better healthcare provision in the future, it will be equally important for countries in
the Middle East to focus on improving the delivery of healthcare services and associated business
processes such as the development of primary care and specialised care services. This issue will be debated at the Leaders in Healthcare Conference during the 39th Arab Health
Exhibition & Congress from 27 -30 January 2014 at the Dubai International Convention & Exhibition
Center.
According to Professor Lord Darzi of Denham, Hamlyn Chair of Surgery, Director, Institute of Global
Health Innovation, Imperial College London, UK, and speaker at the Leaders in Healthcare
Conference, “The Middle East should move towards specialised care, but in parallel to developing
effective primary care services which should form the basic foundation of a healthcare system. There
is a need to build efficient and disease-specific models of prevention and specialised care that
deliver quality outcomes in the most cost-effective way possible. One example of this is Qatar’s
National Cancer Strategy. This looks at all aspects of cancer prevention and management drawing on
robust international evidence, and is reshaping the treatment and support patients receive. The
Middle East is also increasingly attracting international academic and clinical research talent and
emerging as a location for biomedical research. We are starting to see this feed into the
development of specialised care services and the creation of disease-specific research strategies.”
Healthcare spend in the region is expected to reach $133.19bn in 20181
. Lord Darzi believes that
regional investment opportunities include the development of regional specialist providers,
enhanced primary care services, the development of regionally based capacity to manufacture
pharmaceuticals and medical equipment, and the development of a regional talent pool to reduce
the reliance on imported human capital. These are all growth areas in the region’s healthcare sector. Commenting on this growth trajectory, Steven J. Thompson, Senior Vice President, Johns Hopkins
Medicine and CEO, Johns Hopkins Medicine International says, “Over the past decade Johns Hopkins
Medicine has engaged in a number of exciting and highly successful health care collaborations in the
Middle East. Many government agencies and leading companies in the region have placed a high
priority on increasing the accessibility, quality and safety of health care delivery, as well as on adding
advanced specialty care. More hospitals in the Middle East are becoming world class institutions,
and that trend seems only to be accelerating.”
1 Arabianindustry.com 3 June 2013 http://bit.ly/1bcT9WjScience and technology will play a significant role in enhancing and enabling better healthcare
provision in the future and managing spiraling healthcare costs. “For example, we are already seeing the impact that smartphones and digital applications are having
as a cost effective and patient targeted method of managing chronic diseases like diabetes. These
will change the landscape of primary and community care delivery over the next decade. Personalised medicine will revolutionise healthcare by allowing for the tailoring of treatments to
each patient. Gone will be the days of trial and error; prescribing courses of treatment that do not
work. Through a combination of genomic information, tissue imaging data and clinical outcomes, we
will know what will work for a particular patient with a certain genomic profile,” says Lord Darzi.
-END- Note to Editors
About Arab Health Exhibition & Congress: Arab Health Exhibition & Congress is the largest healthcare event in the Middle East. Established 39
years ago, Arab Health provides a platform for the world’s leading manufacturers, wholesalers and
distributors to meet the medical and scientific community in the Middle East and subcontinent. Arab
Health, organised by Informa Life Sciences Exhibitions, takes place from 27-30 January 2014 at the
Dubai International Convention & Exhibition Centre. With more than 3900 exhibiting companies
from 63 countries and 19 healthcare conferences with an estimated 9000 delegates, Arab Health is a
much anticipated addition to the 2014 medical event calendar. Website: www.arabhealthonline.com
About Institute of Global Health Innovation:
Website: http://www3.imperial.ac.uk/global-health-innovation
About Johns Hopkins Medicine International:
Website: http://www.hopkinsmedicine.org/international/
For press enquires please contact:
Inga Stevens
Senior Communication Manager, Informa Life Sciences Exhibitions
T: +971 4 407 2743
inga.stevens@informa.com

Big Data to drive reduced healthcare costs and improved quality of care in GCC

International case studies to be presented at Big Data Conference at Arab Health 2014
Dubai, UAE: The GCC has all of the necessary factors to enable Big Data to launch with success.
There are several large healthcare systems and regulators bringing together enormous amounts of
data in real time about their patients and populations. The region also has access to cutting edge IT
and mobile technologies to collect and manage the data. More importantly, it is equipped with the
tools and growing talent to perform analytics in the healthcare sector. A panel of international and regional experts will highlight the global outcomes of implementing Big
Data in healthcare during the Big Data Conference at the 39th Arab Health Exhibition & Congress
from 28-29 January 2014 at the Dubai International Convention & Exhibition Centre.
There is a worldwide divide between laboratory scientists who continuously produce new research
findings and medical professionals in their clinical settings who need to be aware of these results.
The same applies to patient medical records that need to be accessible across a number of
specialties. This divide is more pronounced in the developing world due to the lack of conscious
effort to translate research findings into clinical practice through analytics. Bridging this gap through
sharing the latest health information will have a positive impact on patients and can even be
lifesaving.
According to Daniel Whitehead, MENA Healthcare Lead, Booz Allen Hamilton, “Using data analytics
on electronic health records in real time can offer enormous benefits for patients in this region. For
example, predictive analytics can be used to identify which patients are more at risk of life
threatening complications in the ER. Moreover, in the management of chronic diseases using mobile
monitoring applications, Big Data can help identify which behaviours are associated with negative
outcomes and which interventions are most effective.”
“There has been a lot of buzz around the potential for ‘Big Data’ to enable better decision making,”
says Mike Swinford, CEO, GE Global Healthcare Services. “Adding in human insight and process
control with analytical structures is what GE calls the ‘Industrial Internet’; Intelligent Machines –
Intelligent Information – Intelligent People. This is what the Industrial Internet is all about. In
healthcare, this strategic approach is a way to drive optimisation of assets, reduce operational
inefficiencies and improve clinical quality, all while reducing costs.”
According to Dr Abdul Rezzak Hamzeh, Senior Scientific Coordinator, Centre for Arab Genomic
Studies, Dubai, UAE, “A working example of using Big Data in healthcare in the GCC is through the
CTGA (Catalogue for Transmission Genetics in Arabs) database at the Centre for Arab Genomic
Studies in Dubai. The CTGA database is the largest ethnic-based genetic database worldwide and it
currently hosts a collection of over 1600 records of genetic disorders and their related genes. These
records provide good quality coverage of both clinical and molecular aspects of the geneticdisorder, and more importantly they offer comprehensive and updated coverage of research results
on these disorders in Arab populations.”
-END- Note to Editors
About Arab Health Exhibition & Congress
Arab Health Exhibition & Congress is the largest healthcare event in the Middle East. Established 39
years ago, Arab Health provides a platform for the world’s leading manufacturers, wholesalers and
distributors to meet the medical and scientific community in the Middle East and subcontinent. Arab
Health, organised by Informa Life Sciences Exhibitions, takes place from 27-30 January 2014 at the
Dubai International Convention & Exhibition Centre. With more than 3900 exhibiting companies
from 63 countries and 19 healthcare conferences with an estimated 9000 delegates, Arab Health is a
much anticipated addition to the 2014 medical event calendar.
Website: www.arabhealthonline.com
About Booz Allen Hamilton: Website: www.boozallen.com
About GE Global Healthcare:
Website: www.gehealthcare.com
About Arabic Genetic Centre:
Website: www.cags.org.ae
For press enquires please contact:
Weaam El-Ataya
PR & Social Media Executive
Informa Life Sciences Exhibitions
T: +971 4 408 2813
weaam.elataya@informa.com

WT1 as a biomarker to predict relapse in patients with acute leukemia and MDS

Relapse is a major obstacle to maximizing curative potential of allogeneic HCT (aHCT) therapy for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL)) and myelodysplastic syndrome (MDS). It has been shown that relapse can be detected through longitudinal application of quantitative PCR (qPCR) measurement techniques before patients (Pts) develop symptoms and that early intervention to delay or stop relapse can improve patient outcome. However, such tests apply only to a small percentage of Pts with fusion gene transcripts and specific mutations. WT1 has been investigated as a tumor marker in a variety of studies which have shown its association with disease progression and relapse. In our pilot work, based on WT1 kinetics data in a small cohort of Pts, we have shown the striking correspondence of increasing WT1 transcript levels with future relapse and the specific time frame between molecular relapse detected by the WT1 PCR test and hematologic relapse confirmed by clinical observations. Our plan is to establish ranges of WT1 transcript levels characteristic of Pts after aHCT that do not relapse, a high threshold level that can serve as a specific biomarker for relapse with close to or 100% specificity, and a less stringent threshold level with lower specificity to identify more Pts that relapse and at earlier times. We will also define the time interval when relapse is detected molecularly by qPCR methods, and later confirmed morphologically by standard clinical methods. Our hypothesis is that many of the Pts that will ultimately relapse will have a period of minimal residual disease that may be detected by repeated elevations of WT1 not exceeding the determined WT1 threshold levels. The ultimate purpose of our study is to apply this important biomarker as part of standard diagnostic procedures for detection of relapse in the highest-risk individuals – acute leukemia and MDS Pts undergoing aHCT.

FIRST v4.0 - Financial Impact of Recurrence Score Testing

FIRST v4.0 has been designed to

1. Predict the financial implications to a health care plan of adopting the Oncotype DX^® breast cancer assay for use in women with ER-positive early-stage invasive breast cancer.
2. To permit plans to input their own characteristics and expected use of the Oncotype DX breast cancer assay in determining the expected costs to the plan.

Inputs and data sources

Table 3. Inputs used in FIRST v4.0, separated into 8 categories.

Data to inform the default values for many of the inputs were obtained from published materials, either from systematic review of the peer-reviewed literature or from publicly available data from government sources. The Navigation bar of FIRST v4.0 provides user access to information on source data (Figure 6).

Many of the inputs values are assumed to be plan specific, and the user is permitted to change these inputs to fit their individual plan’s characteristics. Ranges have been provided for several of the variables, designed to reflect the variability found in the published sources.

Results and computations

Table 4. FIRST v4.0 outputs

User interface

There are two default value options that differ in their data sources for the frequency of RS risk groups. Figure 6 below shows the base case inputs given default values in which the RS risk group frequencies are based on a meta-analysis of published literature.^{2, 4, 10, 21-32}

Figure 6. FIRST v4.0: Budget impact model inputs



Showing default values: risk group frequency values from literature meta-analysis, base case.

Choosing Genomic health sales data default values changes the RS risk group frequency values (Input no. 4) to 57%, 32%, and 11% for low, intermediate and high risk groups in node negative patients. For node positive patients, the risk group frequencies would be, in the same order, 59%, 33%, and 8%.

Scenario analysis tools include lower bound, upper bound and breakeven analyses. The lower bound tool button models a scenario in which test utilization (Input no. 2) is 80% and the costs associated with chemotherapy (Input no. 7) are increased by 25%. In the upper bound scenario, test utilization is 50% and the costs associated with chemotherapy are decreased by 25%. Figure 7 below shows the results of the base case, lower bound and upper bound scenario analyses for both default values options in an abbreviated and condensed presentation of the results interface.

Figure 7. FIRST v4.0 interface. Budget impact model results
A. Default risk group fequency values: Literature meta-analysis

B. Default risk group frequency values: Genomic Health sales data

All computations – except for computing cost of recurrence – involve simple algebra. For example, the projected number of women per year with node-negative, ER-positive invasive breast cancer is the product of

1. number of covered lives in the plan
2. age-adjusted incidence of invasive breast cancer

The projected number of women per year to be tested is product of

1. number of covered lives in the plan
2. age-adjusted incidence of invasive breast cancer
3. percent of women to be tested with the Oncotype DX breast cancer assay

The costs associated with change in chemotherapy use are computed as product of

1. net change in chemotherapy use due to the Oncotype DX breast cancer assay
2. associated costs for each cost component (drugs, supportive care, or adverse events)

Estimating the effect of the Oncotype DX breast cancer assay on late costs of recurrence involves somewhat more detailed computations. FIRST v4.0 predicts when recurrence occurs, assigns a cost to that recurrence, and then adjusts the cost to net present value in 2010 US dollars, using a fixed annual discount rate of 3%.

Key findings (Budget impact model)

• Every scenario examined results in a reduction in total costs (Table 5).
• Net reduction of adjuvant chemotherapy use results in savings in the costs of chemotherapy drugs, administration, supportive care, and adverse events. (per patient tested per year)
  • Literature-based RS risk group frequency: $5,603 (range $4,202 to $7,004) savings.
  • GHI sales data: $6,744 (range $5,058 to $8,430) savings.
• The humanistic benefits of avoiding adjuvant chemotherapy include preventing early toxicities (nausea and vomiting, alopecia) and late toxicities (development of new primary tumors, ovarian failure, and cognitive dysfunction).

Table 5. Scenarios results summary for a 2 million member plan

References

2. Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score^® assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 2010;11:55-65.

4. Goldstein LJ, Gray R, Badve S, et al. Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol 2008;26:4063-71.

10. Klang SH, Hammerman A, Liebermann N, Efrat N, Doberne J, Hornberger J. Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization. Value Health 2010;13:381-7.

21. Lo SS, Mumby PB, Norton J, et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol 2010;28:1671-6.

22. Asad J, Jacobson AF, Estabrook A, et al. Does Oncotype DX recurrence score affect the management of patients with early-stage breast cancer? Am J Surg 2008;196:527-9.

23. Erb C, Fox K, Patel M. Evaluation of practice patterns in the treatment of node-negative, hormone-receptor positive breast cancer patients with the use of the Oncotype DX assay at the University of Pennsylvania. Abstract #3082. In: 30th Annual San Antonio Breast Cancer Symposium. San Antonio, TX; 2007.

24. Habel LA, Shak S, Jacobs MK, et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res 2006;8:R25.

25. Liang H, Brufsky A, Lembersky B. A retrospective analysis of the impact of Oncotype DX low recurrence score results on treatment decisions in a single academic breast cancer center. Abstract #2061. In: 30th Annual San Antonio Breast Cancer Symposium. San Antonio TX; 2007.

26. Liebermann N, Baehner FL, Soussan-Gutman L, Klang S, Yoshizawa C, Shak S. Evaluation of Recurrence Score, nodal status and traditional clinicopathologic metrics in a large ER positive patient cohort. Abstract #1420. In: 2011 European Society for Medical Oncology. Providence, RI; 2011.

27. Oratz R, Kim B, Chao C, et al. Physician survey of the effect of the 21-gene recurrence score assay results on treatment recommendations for patients with lymph node-positive, estrogen receptor-positive breast cancer. J Oncol Pract 2011;7:94-9.

28. Oratz R, Paul D, Cohn AL, Sedlacek SM. Impact of a commercial reference laboratory test recurrence score on decision making in early-stage breast cancer. J Oncol Pract 2007;3:182-6.

29. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:2817-26.

30. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24:3726-34.

31. Partin JF, Mamounas EP. Impact of the 21-gene recurrence score assay compared with standard clinicopathologic guidelines in adjuvant therapy selection for node-negative, estrogen receptor-positive breast cancer. Ann Surg Oncol 2011;18:3399-406.

32. Thanasoulis T, Brown A, Frazier T. The role of Oncotype DX assay on appropriate treatment for estrogen positive, lymph node negative invasive breast cancer. In: American Society of Breast Surgeons Annual Meeting. New York, NY; 2008.

Validity Assessment of Oncotype DX breast cancer assay economic analyses

Economic validity refers to the completeness, quality, and reliability of the analyses used to assess the economic implications of novel technologies. In 2003, Weinstein et al. outlined the criteria that should be considered when evaluating economic analysis.⁶ Four criteria have been established for systematically evaluating the quality and validity of economic evaluations, details of which are found in the appendix.

Six papers and one letter have been published in peer-reviewed journals on the potential economic implications of the Oncotype DX^® breast cancer assay in four countries (Table 1). Furthermore, six additional studies, representing five countries, have been presented as abstracts. In total, the implications of the Oncotype DX breast cancer assay have been evaluated in eight different countries.

Table 1. Summary of Health Economic Evidence

Economic Implications of Oncotype DX^® in the United States

In the first economic analysis of the Oncotype DX breast cancer assay in node-negative, ER-positive invasive breast cancer patients receiving tamoxifen, Hornberger et al. performed cost-utility analyses using a decision analytic model.⁷Using a Markov model, they forecasted overall survival, costs, and cost-effectiveness of using the Oncotype DX breast cancer assay results (Recurrence Score) in patients classified as having low or high risk of distant recurrence based on 2004 National Comprehensive Cancer Network^® (NCCN^®) clinical guidelines. Data from a large multicenter clinical trial (NSABP B-14) were analyzed to derive risk classifications based on guideline criteria and the Oncotype DX breast cancer assay. The effect of adjuvant chemotherapy (CT) on distant recurrence-free survival (DRFS) was based on published meta-analyses of CT trials. The analysis took a societal perspective, considering survival, quality of life, and relevant costs. Results showed fifty-three patients (8%) were classified as having low risk of distant recurrence by NCCN guidelines and the Oncotype DX breast cancer assay reclassified 15 of these patients (28%) to the intermediate or high risk groups. The remaining 615 patients (92%) were classified as having high risk of distant recurrence by NCCN guidelines and the Oncotype DX breast cancer assay reclassified 300 of these patients (49%) to low risk. Among a hypothetical cohort of 100 patients with node-negative, ER-positive early-stage invasive breast cancer (7.9% of whom are NCCN-classified as low risk for distant recurrence), use of the Oncotype DX breast cancer assay was expected to reclassify two patients from low risk to intermediate or high risk and 45 patients from high risk to low risk. Assuming patients with intermediate or high risk receive chemotherapy and patients at low risk do not, the Oncotype DX breast cancer assay was predicted to, on average, increase quality-adjusted survival by 8.6 years and reduce overall costs by $202 828 (Figure 3).

Figure 3. Cost effectiveness of the Oncotype DX breast cancer assay applied to cohort of 100 patients with node-negative, ER-positive early-stage invasive breast cancer

From Hornberger et al. Am J Manag Care 2005.⁷

The Oncotype DX breast cancer assay was cost saving in more than two-thirds of probabilistic simulations, with cost-effectiveness most influenced by the propensity to administer CT based on the Oncotype DX breast cancer assay results, and by the proportion of patients at low risk as defined by NCCN guidelines. Researchers concluded that the Oncotype DX breast cancer assay predicts recurrence risk in node-negative, ER-positive patients with early-stage invasive breast cancer more accurately than current guidelines.²⁰ If applied appropriately, the assay is predicted to increase quality-adjusted survival and save costs.

In a 2007 economic analysis of the cost-effectiveness of the Oncotype DX breast cancer assay, Lyman et al. assessed the efficacy of therapy guided by the Oncotype DX breast cancer assay results (Recurrence Score).⁸ Using data from NSABP studies B-14 and B-20, patients were classified as high (RS ≥31), intermediate (RS 18-30), or low (RS < 18) risk for distant recurrence at 10 years. Cost-effectiveness ratios were estimated for therapy guided by the Oncotype DX breast cancer assay compared with either tamoxifen alone or combined chemotherapy and tamoxifen. Therapy guided by the Oncotype DX breast cancer assay was associated with a gain in individual life expectancy of 2.2 years compared with tamoxifen alone, and with similar life expectancy to that seen with combined chemotherapy and tamoxifen. Therapy guided by the Oncotype DX breast cancer assay was estimated to provide a net cost savings of $2,256 compared with chemotherapy and tamoxifen with an incremental cost-effectiveness ratio of $1,944 per life year saved compared with tamoxifen alone (Figure 4).

Figure 4. Cost-effictiveness of Oncotype DX^® breast cancer assay

From Lyman et al. Cancer 2007.⁸

Researchers concluded that for patients with lymph node-negative, estrogen receptor-positive early-stage invasive breast cancer, treatment decisions based on therapy guided by the Oncotype DX breast cancer assay is associated with greater efficacy and acceptable cost-effectiveness ratios compared with tamoxifen alone. Compared with combined chemotherapy and tamoxifen, therapy guided by the Oncotype DX breast cancer assay is associated with similar efficacy and lower cost.

In 2010, Lo et al. at Loyola University Medical Center published the first prospective study on the decision impact of the Oncotype DX breast cancer assay.²¹ It inquired about reanalysis of the economic implications of the Oncotype DX breast cancer assay with their data. In response, Hornberger et al. applied the data reported by Lo et al. in the previously published decision analytic model and found a saving of more than $300 per patient tested.⁹

Hornberger et al. conducted a subsequent study in collaboration with Humana Inc., a large United States health insurance company, to examine the economic implications of adopting the Oncotype DX breast cancer assay within its health plan.¹⁵ Using published decision impact study of the Oncotype DX breast cancer assay and cost data obtained from retrospective claims analyses of 952 invasive breast cancer patients who were tested with the Oncotype DX breast cancer assay, the study found that, for Humana, the adoption of the Oncotype DX breast cancer assay was cost-saving (Figure 5).

Figure 5. Cost-effectiveness of Oncotype DX^® breast cancer assay adoption to Humana, Inc.

From Hornberger et al. Am J Manag Care 2011.¹⁵

To view the Hornberger et al. 2005 article please visit:http://www.ajmc.com/files/articlefiles/AJMC05MayHornbergr313to.pdf

To view the Lyman et al. 2007 article please visit: http://www3.interscience.wiley.com/cgi-bin/abstract/114124513/ABSTRACT

To view the Hornberger et al. 2011 article please visit: http://jop.ascopubs.org/content/7/3S/e38s.abstract?sid=7c228324-299f-44ff-bfb5-f15726ddfd19

National Comprehensive Cancer Network^® and NCCN^® are registered trademarks of NCCN, which does not endorse any product or therapy.Economic implications of the Oncotype DX^® breast cancer assay outside the United States

The economic implications of the Oncotype DX breast cancer assay have been evaluated in seven countries outside the United States (Table 2).

Table 2. Summary of health economic evidence outside the United States

References

6. Weinstein MC, O'Brien B, Hornberger J, et al. Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR Task Force on Good Research Practices--Modeling Studies. Value Health 2003;6:9-17.

7. Hornberger J, Cosler LE, Lyman GH. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer. Am J Manag Care 2005;11:313-24.

8. Lyman GH, Cosler LE, Kuderer NM, Hornberger J. Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies. Cancer 2007;109:1011-8.

9. Hornberger J, Lyman GH, Chien R. Economic implications of 21-gene recurrence score assay: US multicenter experience. J Clin Oncol 2010;28:e382; author reply e3.

15. Hornberger J, Chien R, Krebs K, Hochheiser L. US insurance program’s experience with a multigene assay for early-stage breast cancer. Am J Manag Care 2011;17:e194-202.

20. Goldstein LJ, Gray R, Badve S, et al. Prognostic Utility of the 21-Gene Assay in Hormone Receptor-Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features. J Clin Oncol 2008.

21. Lo SS, Mumby PB, Norton J, et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol 2010;28:1671-6.

The Oncotype DX Breast Cancer Assay for DCIS Patients

The Oncotype DX Breast Cancer Assay for DCIS is a multi-gene diagnostic assay designed to support personalized treatment planning for patients with DCIS following local excision. The assay provides an individualized estimate of the 10-year risk of local recurrence (DCIS or invasive carcinoma) to help guide treatment decision making in women with ductal carcinoma in situ treated by local excision, with or without tamoxifen.

The Oncotype DX Breast Cancer Assay is performed in the licensed Genomic Health laboratory where the assay was developed. All H&E's are reviewed by board certified surgical pathologists and the DCIS tumor is marked for manual microdissection. The dissected, enriched tumor sample then undergoes RNA extraction. Next, the RNA is analyzed using a technique called real-time RT-PCR (reverse transcriptase-polymerase chain reaction). Finally, the DCIS Score™ result is calculated from the gene expression results.

Advantages of RT-PCR

The Oncotype DX Breast Cancer Assay analyzes the expression of a panel of 21 genes from a tumor specimen using a technique called RT-PCR. A high-throughput, real-time RT-PCR method was developed to analyze the expression of select genes. Unlike routine histopathologic H&E slide review or assessment of immunohistochemical stains for hormone receptors, RT-PCR is sensitive, specific, highly reproducible, and has a wide dynamic range. RT-PCR is a mature technology that is routinely utilized in several clinical applications including viral load testing for HIV.

To quantify gene expression, RNA is extracted from formalin-fixed, paraffin-embedded (FPET) tumor tissue and subjected to DNase I treatment. Total RNA content is measured and the absence of DNA contamination is verified. Reverse transcription is performed and is followed by quantitative TaqMan^® (Roche Molecular Systems, Inc.) RT-PCR reactions in 384-well plates. The expression of each of 16 cancer related genes is measured in triplicate and then normalized relative to a set of five reference genes.

The Oncotype DX Breast Cancer Assay for DCIS patients standardized testing methods have been optimized to minimize variability due to:

• Sources of pre-analytic variability: delay to fixation, choice of fixative, duration of fixation, age of sample

Oncotype DX Assay Development

The Oncotype DX Breast Cancer Assay for DCIS patients was developed in four steps. Each of these steps is described in detail below.

• Optimization of methods for quantifying gene expression in formalin-fixed, paraffin-embedded tissue (FPET)
• Selection of 250 candidate genes from the human genome
• Testing of candidate genes to identify an optimal gene panel for clinical validation
• Prospective clinical validation of the gene panel and DCIS Score result calculation

Step 1. Optimization of methods for quantifying gene expression in formalin-fixed, paraffin-embedded tissue

The ability to work with FPET samples is critical in the U.S., as this is the standard method for tumor preservation and storage. When tissue is preserved in paraffin, the RNA is fragmented. However, the relative ratio of RNA between genes is unchanged. By utilizing RT-PCR techniques, the expression of most genes—relative to a set of reference genes—can be measured. To develop the Oncotype DX Breast Cancer Assay, Genomic Health researchers optimized RT-PCR technology 1) for high-throughput, real-time quantitation of specific RNA in FPET, and 2) to be reproducible regardless of the variability inherent in tumor blocks.

Step 2. Selection of 250 candidate genes from the human genome

Genomic Health researchers relied on numerous sources to identify 250 candidate genes—those possibly associated with breast cancer tumor behavior—from among the approximately 25,000 genes in the human genome.

Step 3. Testing of candidate genes to identify an optimal gene panel for clinical validation

The 250 candidate genes were analyzed in a total of 447 patients from three independent clinical studies in order to identify a panel of genes strongly correlated with distant recurrence-free survival. The selection of the 16 cancer genes used for the Oncotype DX Breast Cancer Assay was based on the results of the three clinical trials, which demonstrated a consistent and strong statistical link between these genes and distant breast cancer recurrence. Five reference genes were identified to normalize the expression of these cancer-related genes. The 21- gene panel described above has been optimized for the DCIS Score, which is calculated from a subset of the genes using a DCIS-specific algorithm and coefficients.

Step 4. Prospective clinical validation of the DCIS Score

The Oncotype DX Breast Cancer Assay gene panel and DCIS Score result calculation were validated in a large, independent, multicenter clinical trial (ECOG E5194). The endpoints and analysis plan were prospectively defined. The results of this study were presented at the San Antonio Breast Conference 2011 and the results of the ECOG E5194 clinical validation study will be published in the near future.

21-Gene Panel Used to Calculate Recurrence Score^® Result

The Oncotype DX Breast Cancer Assay gene panel was selected from the published literature, a genomics database and experiments based on DNA arrays performed on fresh-frozen tissue. The DCIS Score is obtained by performing the Oncotype DX Breast Cancer Assay, using a distinct DCIS algorithm and coefficients that was pre-specified because of its ability to predict recurrence in patients with DCIS regardless of whether adjuvant tamoxifen therapy was given.

Development of the DCIS Score algorithm was based on published results for the Oncotype DX Breast Cancer Assay showing similarity in the expression profiles of the Recurrence Score genes between DCIS and Invasive Breast Cancer (IBC) when both are present within the same patient tumor. The DCIS Score algorithm was developed based on published data obtained from the Kaiser Permanente and NSABP B-14 studies in which the proliferation gene group, PR and GSTM1 were found to predict distant recurrence regardless of whether adjuvant tamoxifen therapy was given. This DCIS Score was subsequently validated as a predictor of local recurrence in patients from the ECOG E5194 study. These results were presented at the San Antonio Breast Conference 2011.

Donare per curare, il primo Rapporto sulla povertà sanitaria

La crisi morde e mette in discussione gli stili di vita. Diminuiscono i consumi delle famiglie che riducono la spesa alimentare, quella per l’abbigliamento e, sempre più spesso, quella sanitaria. Meno cibo, meno vestiti, meno medicine. Poiché il numero dei poveri assoluti, in cinque anni, dal 2007 al 2012, è aumentato del 60% arrivando a contare 4 milioni e 800 mila persone, quello che per le cronache è un problema economico rischia di trasformarsi anche in una questione di salute.

E’ quanto emerge dal primo Rapporto sulla povertà sanitaria e sulla donazione dei farmaci, “Donare per curare”, promosso dalla Fondazione Banco farmaceutico e presentato questa mattina a Roma. Lo studio è stato curato dall’Osservatorio nazionale sulla Donazione dei farmaci, composto da ricercatori dell’Università Cattolica e dell’Università statale di Milano, che hanno incrociato una serie di dati: quelli forniti da fonti statistiche ufficiali, quelli delle Giornate annuali per la raccolta del farmaco, quelli delle donazioni fatte dalle aziende di settore e le informazioni dei sistemi di monitoraggio degli oltre 1.500 enti caritativi della rete del Banco farmaceutico.

Negli ultimi anni, è aumentato il numero degli italiani che, per curarsi, si sono rivolti agli enti caritativi chiedendo aiuto: 680 mila persone nel 2013, il 57% delle quali italiane, scrivono nel Rapporto i ricercatori.

Le famiglie in Italia spendono, in media, il 3,7% del loro budget in sanità, cioè 92,45 euro al mese, destinando 44 euro ai farmaci. Quelle povere, invece, per le spese sanitarie utilizzano il 2% del bilancio familiare, cioè 16,34 euro, di questi 12,50 euro sono per l’acquisto di medicine.

Il diritto alla salute è un diritto incomprimibile. Eppure, viene sacrificato dalla parte più fragile della società, proprio lì dove si registra un aumento delle malattie, connesse a stili di vita e a rischi ambientali. La lista degli svantaggiati è lunga: immigrati, rifugiati, anziani con pensioni minime, adulti che hanno perso lavoro, famiglie numerose, ma anche giovani. Tutti cittadini sul piano costituzionale, ricorda don Francesco Soddu, direttore della Caritas, “tuttavia cittadini dimezzati sul piano politico e della salute”.

Nei primi nove mesi del 2012, spiega Giancarlo Rovati, professore di Sociologia generale che ha coordinato i ricercatori dell’Osservatorio, la spesa farmaceutica complessiva in Italia è stata pari a 15 milioni circa, di cui 9 milioni e duecento mila euro a carico del sistema pubblico per una spesa pro capite di 17 euro. Solo il 61% è stato, cioè, a carico del Servizio sanitario nazionale, mentre il restante 38,5% è stato pagato dalle famiglie che hanno sborsato 5 milioni e 700 mila euro. Una contrazione del contributo da parte dello Stato che ha costretto sette famiglie su dieci a ridurre la propria spesa sanitaria.

Non tutti ce la fanno. “In farmacia – racconta Annarosa Racca, presidente di Federfarma – la crisi si vive direttamente. Spesso ci vengono chiesti medicinali alternativi e meno costosi, talvolta c’è chi rinuncia addirittura al farmaco”. Un’emergenza, quella della “povertà sanitaria – le fa eco Paolo Gradnik, presidente della Fondazione Banco farmaceutico – con la quale siamo costretti a fare i conti quotidianamente”.

Il Banco farmaceutico, pertanto, cerca di rispondere ai bisogni delle persone indigenti, approvvigionando gli enti territoriali di assistenza, attraverso tre canali: le Giornate per la raccolta del farmaco (GRF), durante le quali i cittadini possono offrire farmaci da automedicazione, le donazioni da parte delle aziende farmaceutiche, che possono donare anche farmaci con obbligo di prescrizione medica, il recupero di farmaci validi (cioè non scaduti).

In sette anni, tra il 2007 e il 2013, la percentuale dei farmaci donati ha registrato un aumento del 241%, in numeri assoluti, sono stati raccolti 1 milione 162 mila farmaci, il 23% durante le GRF e il 1.345% donati dalle aziende farmaceutiche. Nel 2013, in particolare, la Fondazione ha distribuito medicinali per un valore di 30 milioni di euro. A dati così incoraggianti, però, corrisponde la diminuzione della capacità di soddisfare le richieste di farmaci: ne è aumentato il bisogno.

La ricerca della Fondazione del Banco farmaceutico evidenzia un ulteriore dato. Lo sbilanciamento territoriale. Infatti, lo scorso anno, hanno aderito alla GRF 3.366 farmacie distribuite su tutto il territorio nazionale, eccezion fatta per il Molise. Il tasso di adesione è stato più consistente al Nord, la regione più attiva è stata la Lombardia. Le donazioni raccolte sono state utili a rispondere al bisogno di 1.506 organizzazioni caritative, diffuse per il 22% in Lombardia, per il 12,5% in Emilia Romagna, per l’11,4% in Piemonte e per l’8,8% in Veneto.

I presidenti di Assogenerici, Enricue Hausermann, di Assosalute, Stefano Brovelli, e il presidente delle Acli, Gianni Bottalico, hanno appoggiato l’iniziativa del Banco farmaceutico e convenuto sulla necessità di proseguire lungo del strada del lavoro di squadra, fatto di alleanze virtuose.

“La Fondazione, conclude Gradnik, stando all’attuale congiuntura economica, non chiede aiuti pubblici in termini monetari”, ma rivolge l’appello a Marcella Marletta, direttore generale del Ministero della Salute, e al senatore Andrea Mandelli, presidente della Federazione degli Ordini dei farmacisti, affinchè diventi legge la proposta di rendere più semplice e fluido il transito dei farmaci lungo l’intera filiera della donazione, agevolando il canale privilegiato delle imprese che recupererebbero le eccedenze di produzione.

Trasformare in un bene sociale ciò che fino a oggi è stato uno spreco si potrà rispondere, ricorda don Soddu, all’invito di papa Francesco a trovare nuove strade per occuparsi creativamente e cooperare con efficacia affinchè i poveri vivano con dignità e a tutti sia garantita l’inclusione.
La Giornata per la raccolta del farmaco 2014 sarà organizzata il prossimo 8 febbraio.