Natural history of disease / population screening

Principles of Epidemiology for Public Health (EPID600) Natural history of disease / population screening Victor J. Schoenbach, PhD home page Department of EpidemiologyGillings School of Global Public HealthUniversity of North Carolina at Chapel Hill www.unc.edu/epid600/ Natural history; population screening

SHE shouldn’ts (courtesy of www.flylady.net # 8: SHE's shouldn't let themselves get too tired – Last week I was going over some homeschooling with my 11yo DD when I realized I hadn't seen or heard my fast-crawling 13-month old DD in a while. I said, "Anyone know where the baby is?" My older daughter just looked at me and said, "Mom?" Lo and behold, I'm nursing the baby! - in Colorado

What not to say in your job interview “Herb Greenberg, a leading authority on work-related personality testing, keeps a list of the dumbest things people have told his corporate clients during recent job interviews.” (Cheryl Hall, Knight Ridder, Herald-Sun, 1/26/2003: F2) (Greenberg is the 73-year-old chief executive officer of Caliper, in Princeton NJ)

Have you ever thought of saying … • “I will definitely work harder for you than I did for my last employer.” • “I don’t think I’m capable of doing this job, but I sure would like the money.” • “Do you know of any companies where I could get a job I would like better than this one?”

Have you ever thought of saying … • “I’m quitting my present job because I hate to work hard.” • An apology for yawning “I usually sleep until my soap operas are on.”

Disease natural history and prevention • Knowledge of the natural history of disease is fundamental for effective prevention • Levels of prevention: • Primary – prevent the disease [Primordial – prevent the risk factors] • Secondary – early detection and Rx • Tertiary – treat and minimize disability Natural history; population screening

Disease natural history & population screening • Phenomenon of disease • - What is disease? • - Natural history of disease • Requirements for screening programs • Detection of disease • - Sensitivity • - Specificity • Interpreting diagnostic & screening tests • - Predictive value Natural history; population screening

Phenomenon of health: what is health? • World Health Organization: • “a state of complete physical, mental, [and] social well-being and not merely the absence of disease or infirmity” Natural history; population screening

Phenomenon of disease: what is disease? • Difficult to define, e.g.: • “a type of internal state which is either an impairment of normal functional ability–that is, a reduction of one or more functional abilities below typical efficiency–or a limitation on functional ability caused by environmental agents” • (C. Boorse, What is disease? In: Humber M, Almeder RF, eds. Biomedical ethics reviews. Humana Press, Totowa NJ, 1997, 7-8 (quoted in Temple et al., 2001) Natural history; population screening

Phenomenon of disease: what is disease? • Difficult to define, e.g.: • “a state that places individuals at increased risk of adverse consequences” • (Temple LKF et al., Defining disease in the genomics era. Science 3 Aug 2001;293:807-808) Natural history; population screening

Phenomenon of disease: natural history • Disease is a process that unfolds over time • Natural history – sequence of developments from earliest pathological change to resolution of disease or death Natural history; population screening

Phenomenon of disease: natural history • Induction – time to disease initiation • Incubation – time to symptoms (infectious disease) • Latency – time to detection (for non-infectious disease) or to infectiousness Natural history; population screening

Natural history of coronary heart disease “Spontaneous atherosclerosis” “Lipid lesion” Fibrointimal lesion Plaque growth, occlusion Accumulation of lipids and monocytes, toxic products, platelet adhesion(adolescence) Chronic minimal injury (blood flow, CHL, smoking, infection?) (youth?) Migration & proliferation of smooth muscle cells (adulthood) Disruption thrombi (adulthood) Natural history; population screening

Natural history is central to screening Pre-detectable Detectable, preclinical Clinical Disability or death Age: 35 45 55 65 75 Clinical detection Possible detection via screening Natural history; population screening

Population screening “application of a test to asymptomatic people to detect occult disease or a precursor state” (Alan Morrison, Screening in Chronic Disease, 1985) Natural history; population screening

Population screening • Immediate objective of a screening test – to classify people as being likely or unlikely of having the disease • Ultimate objective: to reduce mortality and morbidity Natural history; population screening

Test that can help save your life Natural history; population screening

Requirements for a screening program 1. Suitable disease 2. Suitable test 3. Suitable program 4. Good use of resources Natural history; population screening

1. Suitable disease • Serious consequences if untreated • Detectable before symptoms appear • Better outcomes if treatment begins before clinical diagnosis Natural history; population screening

2. Suitable test • Detect during pre-symptomatic phase • Safe • Accurate • Acceptable, cost-effective Natural history; population screening

3. Suitable program • Reaches appropriate target population • Quality control of testing • Good follow-up of positives • Efficient Natural history; population screening

4. Good use of resources • Cost of screening tests • Cost of follow-up diagnostic tests • Cost of treatment • Benefits versus alternatives Natural history; population screening

Screening for Breast Cancer U.S. Preventive Services Task Force December 4, 2009 • Summary of Recommendations • The USPSTF recommends biennial screening mammography for women aged 50 to 74 years.Grade: B recommendation. • The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient's values regarding specific benefits and harms. Grade: C recommendation. • The USPSTF recommends against teaching breast self-examination (BSE).Grade: D recommendation. • . . . Natural history; population screening

Revisiting the USPSTF Breast Cancer Screening Guidelines: Ethics, and Patient Responsibilities David Shabtai Faculty Peer Reviewed In a bold move, the U.S. Preventive Services Task Force recently changed their breast cancer screening guidelines – recommending beginning screening at age 50 and even then only every other year until age 75. Bold, because the Task Force members are certainly aware of the media circus that ensued when in 1997, an NIH group issued similar guidelines, prompting comparisons to Alice in Wonderland. Natural history; population screening

Mammography Wars September 10, 2010 Recommended Weekend Reading By NATASHA SINGER “Can we trust doctors’ recommendations on cancer screening, given that the medical profession has a vested financial interest in treating patients? That is one of the questions posed in a provocative article this week in The New England Journal of Medicine that looks at the fallout last year after a government panel recommended that women start having mammograms later in life and less frequently.” Natural history; population screening

Who should get a mammogram? September 29, 2010 Mammogram Benefit Seen for Women in Their 40s By GINA KOLATA Researchers reported Wednesday that mammograms can cut the breast cancer death rate by 26 percent for women in their 40s. But their results were greeted with skepticism by some experts who say they may have overestimated the benefit. Natural history; population screening

What should we pay for? Newsweek The Mammogram Hustle There is no evidence digital mammograms improve cancer detection in older women. But thanks to political pressure, Medicare pays 65 percent more for them. This story was reported and written by Center for Public Integrity. Natural history; population screening

New U.S. analysis backs annual breast screening By Julie Steenhuysen CHICAGO | Wed Jan 26, 2011 12:26pm EST (Reuters) - A new analysis of evidence used by a U.S. advisory panel to roll back breast cancer screening guidelines suggests it may have ignored evidence that more frequent mammograms save more lives, U.S. researchers said on Tuesday. Natural history; population screening

AJR: USPSTF mammo recommendations could cost 6,500 lives yearly “The U.S. Preventive Services Task Force (USPSTF) “chose to ignore the science available to them” and brought about “potential damage to women’s health” in its 2009 recommendations for more limited mammography screening, costing an estimated 6,500 deaths in women each year, a study published in the February issue of the American Journal of Roentgenology concluded.” Natural history; population screening

Survival time after diagnosis – lead time Pre-detectable Detectable, preclinical Clinical Disability or death Age: 35 45 55 65 75 Lead time Clinical detection Possible detection via screening Natural history; population screening

Survival time must increase > lead time Pre-detectable Undetected (no screening) Clinical diagnosis & treatment Disability or death Survival time after diagnosis Pre-detectable Early detect, diagnosis, & treatment Monitoring for recurrence ? Lead time Age: 35 45 55 65 75 Natural history; population screening

Slowly progressing diseases are easier to detect by screening Pre- detectable Clinical diagnosis, treatment Disability or death Survival time after diagnosis Pre-detectable Detectable, pre-clinical Clinical diagnosis & treatment Disability or death Survival time after diagnosis Age: 35 45 55 65 75 Natural history; population screening

Early detection may over-diagnose Pre-detectable Undetected (no screening) Mild or no symptoms Favorable outcome Survival time after diagnosis Pre-detectable Early detect, diagnosis, & treatment Monitoring for recurrence Favorable outcome Survival time after dx Age: 35 45 55 65 75 Natural history; population screening

Screening test • Reliable – get same result each time • Validity – get the correct result • Sensitive – correctly classify cases • Specificity – correctly classify non-cases • [screening and diagnosis are not identical] Natural history; population screening

Reliability • Repeatability – get same result • Each time • From each instrument • From each rater • If don’t know correct result, then can examine reliability only. Natural history; population screening

Reliability • Percent agreement is inflated due to agreement by chance • Kappa statistic considers agreement beyond that expected by chance • Reliability does not ensure validity, but lack of reliability constrains validity Natural history; population screening

Validity: 1) Sensitivity Probability (proportion) of correct classification of cases Cases found/all cases Natural history; population screening

Validity: 2) Specificity Probability (proportion) of correct classification of noncases Noncases identified / all noncases Natural history; population screening

Remember this slide? 2 cases / month O O         O O O O O O O O O O Natural history; population screening

Pre-detectable preclinical clinical old O O         O O O O O O O O O O O O O Natural history; population screening

Pre-detectable pre-clinical clinical old O O O O O         O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O Natural history; population screening

What is the prevalence of “the condition”? O O O O O         O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O Natural history; population screening

Sensitivity of a screening test Probability (proportion) of correct classification of detectable, pre-clinical cases Natural history; population screening

Pre-detectable pre-clinical clinical old (8) (10) (6) (14) O O O O O         O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O Natural history; population screening

Correctly classifiedSensitivity: ––––––––––––––––––––––––––– Total detectable pre-clinical (10) O O O O O         O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O Natural history; population screening

Specificity of a screening test Probability (proportion) of correct classification of noncases Noncases identified / all noncases Natural history; population screening

Natural history of disease / population screening