Simple.Scientifically Informed Medical Practice and LearningSuzana Alves da Silva, MD, MSc, PhD, FNYAM

2014 TEACH Workshop

T H E S E C T I O N O N

Evidence Based Health CareO F T H E N E W Y O R K A C A D E M Y O F

M E D I C I N E

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Therapy

Diagnosis

Prognosis

Harm

What we know?

P I C OClinical Problems

Chatterji, M; Graham, M; Wyer, P. Mapping Cognitive Overlaps Between Practice-Based Learning and Improvement

and Evidence-Based Medicine: An Operational Definition for Assessing Resident Physician Competence. 2009

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Likelihood Performance Utility

What is new?

Imp

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Pre

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of

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me

Fre

qu

ency

o

f o

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Therapy

Diagnosis

Prognosis

Harm

Silva, S and Wyer P. The Roadmap: a blueprint for evidence literacy within a Scientifically Informed Medical Practice and Learning Model. 2012

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Why this is so important?

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Likelihood issue on therapy

• An elderly man is brought to the emergency room from a nursing home. He is febrile, hypotensive, anuric, minimally responsive. Medical and nursing staffs are preparing to implement an advanced protocol for sepsis care when the patient’s daughter arrives. The daughter wants to know “So, if you give him the most intense treatment, how likely is it that he will survive? It doesn’t make sense if he is likely to die anyway!”

This scenario converges on an issue of the absolute probability of survival given maximal, evidence-based, interventions.

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Utility issue on prognosis

• A 40 year old woman is seeing her primary care physician. Her mother has recently been diagnosed with Alzheimer’s disease. She is concerned about the possibility that it could happen to her. The physician advises that there is a genetic test that could eliminate that likelihood. However, the woman expresses ambivalence, saying, “I am not sure I want to know.”

This scenario involves a trade-off between risks versus benefits of sharing the results of a prognostic information.

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Performance issue on therapy

• A medical director of a health care organization is considering inclusion of BRCA1 within a panel of molecular biomarkers for optimization of individualized care of women with diagnosed breast cancer with respect to hormonal therapy, immune-therapy or chemo-therapy. His first question is what is the accuracy of BRCA1 mutation to predict that a women with cancer will in fact respond to a specific therapeutic regimen.

This scenario involves predicting the likelihood of benefit from a treatment if the predictor is present. It calls for information regarding the predictive performance of criteria such as a biomarker in modifying the probability of benefit from a therapeutic option.

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Levels of efficacy of Dx imaging tests

• 1. Proof of concept—Do novel marker levels differ between subjects with and without outcome?

• 2. Prospective validation—Does the novel marker predict development of future outcomes?

• 4. Clinical utility—Does the novel risk marker change predicted risk sufficiently to change recommended therapy and to improve clinical outcomes?

• 6. Cost-effectiveness—Does use of the marker justify additional costs of testing and treatment?

Phases of novel cardiac markers

• diagnostic accuracy, sensitivity, and specificity associated with interpretation of the test.

• whether the information produces change in the referring physician’s diagnostic thinking.

• effect of the information on the patient management plan and on patient outcomes.

• societal costs and benefits of a diagnostic imaging technology.

Hlatky. AHA 2009 Fryback and Thornbury. 1991

Likelihood

Performance

Utility

Performance

Utility

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= Randomized Trials

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“My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer… Once I knew that this was my reality, I decided to be proactive and to minimize the risk as much as I could.”

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Scenario

Chief Medical Executive

PhysicianHealthy Patient

HMOs being pressured for the inclusion of BRCA mutation testing for screening of women with high risk of breast cancer.

Many primary care physicians are ordering BRCA mutation testing to their patients or referring them for genetic counseling without knowing exactly what to do with it.

Many patients with family history of cancer want to be tested for BRCA mutation. Many wonder about preventive surgery or chemotherapy on top of surveillance.

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BRCA1 for screening

Executive Physician Patient• How the organization will

support that• Costs?• Medical staffs?

• Reliability• Costs, who pays?• Screening criteria• Prevalence• Performance• Descendings?• Screening versus surgery?

• Mortality morbidity QOL

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BRCA1 for screening

Executive Physician Patient

L

How many women with high risk of breast cancer? How likely is the development of

breast cancer if BRCA1(+) and (-)? How many litigations?

What is the uncertainty of the information on the risk of breast cancer? Does it

apply to this patient?

What is my risk of breast cancer?

P

How accurate is BRCA1 mutation to predict breast cancer in such groups of

women?

For how many times the presence of BRCA1 increases my risk of

breast cancer?

UIf we tested them all for BRCA1

mutation, would it decrease costs?

Preventive mastectomy would decrease the risk? If

so, for how much?

Should I do preventive mastectomy to

minimize my risk?

15Source: 1. Senkus. European Society of Medical Oncology. 2014. 2. Risk Assessment, Genetic Counseling, and Genetic

Testing for BRCA-Related Cancer: U.S. Preventive Services Task Force Recommendation. 2013. 3. Berliner. National

Society of Genetic Counselors 2013

Breast Cancer || Ovarian Cancer

Women in general

Preventive surgery will drop the risk of cancer by ~ 90%

Little info about the effect of chemoprevention or close surveillance

Little info about impact on death

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Why this is so important?

• Recognition of questions of importance to patients, managers and policy makers in a fashion that facilitates the use of clinical research to inform the corresponding decisions.

• Provide guidance regarding how to explore and interpret patient and stakeholder expressions of the concerns that will maximally inform decisions.

• Categorization of clinical research designs in relationship to different types of clinical questions in a way that embraces the full spectrum of clinically relevant research.

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Why this is so important?

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Thank you!

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Therapy Utility

P In high risk patients, BRCA1+, for how much

I preventive surgery

C compared to surveillance

O decreases patient important outcomes?

Therapy FrequencyIn BRCA1+ patients

who are submitted to preventive surgery

what is the expected likelihood of cancer and death?

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Prognosis Utility

P In high risk patients,

I does BRCA mutation testing

C compared to usual care

O decrease patient important outcomes?

Prognosis FrequencyIn high risk patients,

who are BRCA1+ carriers

what is the expected likelihood of cancer and death?