WHI, Nurses and SWANs: Do Big Clinical Trials Inform Personalized Care? KIRTLY PARKER JONES MD

Transcription

1 WHI, Nurses and SWANs: Do Big Clinical Trials Inform Personalized Care? KIRTLY PARKER JONES MD

2 Conflicts? No financial conflicts of interest (Dr. Jones is a post menopausal female reproductive endocrinologist which may color everything)

3 Objectives Discuss the main outcomes of the Nurses Health Study when it comes to menopausal treatment Discuss the main outcomes of the Women s Health Initiative as applied to menopausal hormone therapy Discuss the findings of the Study of Women Across the Nation with respect to the menopausal transition Apply findings from above to the care of individual women

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5 Nurses Health Study STARTED ,000 PARTICIPANTS

6 Nurses Health Study The names and addresses of 238,026 nurses who fulfilled the eligibility criteria were obtained in 1972 from the American Nurses' Association, with approval from the state boards of nursing. Married registered nurses, aged 30 to 55 in 1976

7 Focus Contraceptive methods, smoking, cancer and heart disease Has expanded to include lifestyle, behaviors, and more than 30 diseases Follow up every two years include menopause and hormone use

8 Outcomes (continuing): estrogen users Slight decrease in coronary heart disease Decrease in hip fractures Slight decrease in colon cancer Slight increase in breast cancer Slight increase in venous thrombosis Plus hundreds of other studies and outcomes

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11 Women s Health Initiative RISKS AND BENEFITS OF ESTROGEN AND PROGESTIN IN HEALTHY POSTMENOPAUSAL WOMEN: PRINCIPLE RESULTS FROM THE WOMEN S HEALTH INITIATIVE RANDOMIZED TRIAL JAMA JULY 17, 2002

12 HRT and Mortality WHI trials consistent with observational studies indicating that HRT may reduce total mortality when initiated soon after menopause 30% reduction over course of study when data from WHI ET and HRT combined for women initiated before 60 ( my smart patients would ask 30% of what?) (no significant difference over a lifetime, though)

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14 HRT Risks: Numbers for the Patient New HRT Starts in women One extra blood clot per 2000 women per year One extra breast cancer detected per 2000 women per year (no increase in estrogen only) No differences in deaths over 5 years between women who take HRT and women who don t

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17 Statistical vs Clinical Difference Statistical differences are easy to define: eg P<.05, or, even better, P<.01 Clinical Differences are harder to define but you know them when you see them The Kitchen Table Rule or Parker s Rant

18 Parker s Rant Big studies allow significant statistical differences to be made in the face of insignificant clinical differences Big studies don t tell us how to take care of one patient Kirtly Parker Jones MD ; Kitchen Table Dialogues. Every month, every year

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20 Study of Women Across the Nation (SWAN) CHARACTERIZE THE MENOPAUSAL TRANSITION 3,302 WOMEN WOMEN WERE PREMENOPAUSAL PARTICIPANTS SELF-IDENTIFIED AS AFRICAN- AMERICAN (28%), CAUCASIAN (47%), CHINESE (8%), HISPANIC (8%), OR JAPANESE (9%).

21 SWAN Annually for ten years and are every other year Multi-disciplinary focus The most comprehensive characterization of the health and the physiologic and psychosocial changes from pre- to postmenopause in a community based sample. Santoro N et al. Obstet Gynecol Clin N America. Sept 2011; 38(3):

22 SWAN Recurring Themes Psychological, physiological, and social outcomes of changes in the menopausal transition are primarily functions of: 1. Race and ethnicity 2. Socioeconomic status 3. BMI The Late Peri-menopause (3 months after last period) is a critical time when the biological effects of the transition are consistently observed Santoro N et al. Obstet Gynecol Clin N America. Sept 2011; 38(3):

23 How do big studies inform personalized medicine? NOT MUCH

24 2010 Endocrine Society Statement:JCEM Supplement July 2010

25 2010 Endocrine Society Scientific Statement:JCEM Supplement July 2010

26 BREAKTHOUGH VS ME TOO What studies really demonstrate a breakthrough or a paradigm change? Relative risk of 8 (the risk of lung cancer in smokers vs non smokers) 100 patients randomize 80% improved on drug 10 percent improved on placebo

27 Greene JA, Loscalzo J. NEJM. December 11, 2017; 377(25):

28 Biopsychosocial Model George Engel 1977

29 Greene and Loscalzo. Putting the Patient Back Together Social Medicine, Network Medicine, and the Limits of Reductionism. NEJM. December 2017

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31 The Lady in your Clinic NOT A NURSE HAS PROBLEMS WITH HER HORMONES HAS OTHER MEDICAL PROBLEMS

32 Putting the Patient Back Together in the age of the EMR Read the EMR in advance Internal Medicine s notes Psychiatry s notes Meaningful questionnaires Filled out in advance Looked at in advance

33 Let the Patient Tell Their Story Uninterrupted listening for at least 3 minutes What does SHE think is causing the problem What does SHE think are her biggest challenges in feeling better What does SHE think are her biggest strengths in getting better

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35 FOLLOW UP If you prescribed something animal, vegetable, or mineral (diet, exercise, smoking cessation, a therapist, a medication) Give her a call. Your MA could say Dr. Jones wanted me to check in with you to see how your.[estrogen] was working for you did you take it? any side effects? Without a call, you have no idea what went on The drug not taken is engraved in the EMR for ever [an unsolicited call that isn t a Press Ganey is always welcome}

36 HRT: NAMS 2017 Position Statement Change from: smallest dose for shortest time To Risk: benefit ratio is very different from patient to patient and large long term studies do not show clinically significant increase in risks Decisions should be made individually for each patient (this takes time and an informed patient and physician) SEE NAMS website for clinical tools for patients and physicians

37 Beer s List: Potentially harmful drugs for the elderly * Estrogen (oral,transdermal), with or without progestin (avoid in most elderly, high risk use in the elderly per CMS quality measures) Risks: Breast cancer, endometrial cancer, worsening of incontinence; no cardioprotective; lacks cognitive protection Alternatives: low-dose vaginal estrogens acceptable for vaginal symptoms and prevention of lower urinary tract infections. For vasomotor symptoms, SSRI (not paroxetine), SNRI, gabapentin. *Greater than or equal to 65 years old

38 HRT after 65: NAMS position statement Use of HT should be individualized and not discontinued solely based on a woman s age. The decision to continue or discontinue HT should be made jointly by the woman and her healthcare provider. Menopause, Vol. 22, No. 7, 2015

39 For All Women (and you guys) Live in rooms full of light, avoid heavy food, be moderate in the drinking of wine, take massage, baths, exercise and gymnastics, change surroundings and take long journeys, strictly avoid frightening ideas, indulge in cheerful conversation and amusements, listen to music A. Cornelius Celsus Physician, 1st Century AD

40 Lead a Purposeful Life

41 U Shaped Curve of Happiness *note the scale.

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44 Recommended Reading: Postmenopausal Hormone Therapy An Endocrine Society Scientific Statement JCEM Supplement July 2010 North American Menopause Society: menopause.org Click publications and go to position statements : 2017 Hormone Therapy 2015 Non Hormonal Therapy 2014 Algorithm and mobile app for menopausal symptom management: a clinical decision support tool