Clinician Conceptualization of the Benefits of Treatments for Individual Patients

Key Points Question How do clinicians conceptualize the benefits of treatments for common diseases? Findings In this survey study of 542 clinicians, most respondents significantly overestimated the benefits of common therapies. Clinicians who conceptualized a greater chance of benefits of therapy were more likely to treat similar patients in their practice. Meaning In this study, most clinicians were not well prepared to estimate individual patient chance of benefit, suggesting that an improved understanding of the effects of treatments could lead to more precise use of therapies and better patient outcomes.

To identify the best evidence-based information from the literature regarding probability of a disease outcome and impact of treatment on individual patients 1 , we used a hierarchical method.
1. Data was first sought from high-quality recent systematic reviews, meta-analyses, and/or guidelines. 2. If only older systematic reviews, meta-analyses, and/or guidelines were available with newer high-impact studies after publication, we considered data from both (attempting to understand most accurate numbers for current technology/practice) 3. If no systematic reviews, meta-analyses, and/or guidelines were available, we used data from commonly cited studies based on citations in recent guidelines and creating weighted averages by consensus. The expert panel of physicians overseeing the study was presented with best evidence identified and settled on evidence-based answers presented in results.
Of note, we evaluated recommendations in guidelines around treatment for each individual case. These will not be part of the primary analysis but will likely inform our understanding of results. Each question was written to capture an area with some uncertainty in standard practice-when patient shared decision making would be important.
Quotes are often included in this document. They will mostly be removed from the final appendix but are present to make it easier to evaluate evidence.
Consider Mr. Miller, a 62-year-old man with well-controlled hypertension on aspirin with new atrial fibrillation. He has no particular preference for treatment and wants your advice.
a. What is Mr. Miller's risk for stroke in the next year with no change in therapy?
To determine the probability of stroke in a patient with atrial fibrillation, we found clinical prediction scores to be the best validated method. CHA2DS2-VASc is the most accepted score for atrial fibrillation. It gives a point for, hypertension, which would give Mr. Miller a 1.3% risk of stroke in the next year. 2 The CHA2DS2-VASc score is not completely accurate 3 , so we gave a range around the estimate of a relative 50% higher or lower to 0.6%-2.0% absolute risk.
There's controversy about if aspirin decreases risk of stroke in Afib. We modified the risk of stroke lower to capture this uncertainty. 4 So, his risk of stroke could be as low as 0.4% In summary, risk of stroke in one year for this patient is 0.4% -2.0% b. What would you tell Mr. Miller is the chance that warfarin will prevent him from having a stroke in the next year?
The benefits of treating atrial fibrillation with anticoagulation to prevent stroke has been reviewed. The most recent review was Steinberg BA, Piccini JP. 5 Which referred back to a systematic review by Hart et al. 6 This review identified a 39% RRR compared to aspirin, and others have referenced a 50% reduction in comparison to placebo, so the treatment benefit would be 39%-50% relative risk reduction which would translate to a 0.16%-1.0% benefit to Mr. Miller directly. The proportion of that 10-year risk that is in the first 5 years is likely 1/3-2/3 of the 10-year risk. So, 1/3 of the lower bound of 10-year risk is 7.6% = 2.53% And 2/3 of the upper bound of 10-year risk 17.7% = 11.8% In summary, risk of a cardiovascular event over 5 years for this patient is 2.5-11.8% b. What would you tell Mr. Davis is the chance that antihypertensive therapy will prevent him from having a cardiovascular event within 5 years?
The effect of treatment of his hypertension was identified through a recent systematic review. 9 These effects are consistent with those identified when this patient is considered using AHA/ACC risk score. ASCVD calculator provides HTN relative risk reduction ~25-26% Treatment benefit per systematic review: OR 0.72 9 or 28% relative reduction, so absolute benefit would be 28% of 2.53%-(28% of 11.8%). However, this systematic review combined stroke and cardiovascular events, and the effect was non-significant for cardiovascular events alone, so estimates of benefit include 0%. The relative risk reduction was 0-28% and the absolute benefits to Mr. Davis are 0%-3.3% Do Guidelines recommend treatment?
Guidelines are variable. Cardiology guidelines recommend treatment of patients "Use of BP-lowering medication is recommended for primary prevention of CVD in adults with no history of CVD and with an estimated 10-year ASCVD risk <10% and an SBP of 140 mm Hg or higher or a DBP of 90 mm Hg or higher", whereas primary care guidelines (ACP/AAFP) do not recommend treatment with systolic blood © 2021 Morgan DJ et al. JAMA Network Open.
pressure below 150 without increased cardiovascular risk. 10,11 ACP/AAFP: "ACP and AAFP recommend that physicians initiate treatment in adults aged 60 years old and older with persistent systolic blood pressure at or above 150 millimeters of mercury (mm Hg) to achieve a target systolic blood pressure of less than 150 mm Hg to reduce the risk of mortality, stroke, and cardiac events." "ACP and AAFP recommend that physicians consider initiating or intensifying pharmacological treatment in some adults aged 60 years old and older at high cardiovascular risk, based on individualized assessment, to achieve a target systolic blood pressure of less than 140 mm Hg to reduce the risk of stroke or cardiac events. a. How likely is Mrs. Wilson to have a hip fracture in the next 5 years with no additional treatment?
Chance of hip fracture is less than 1%.
The FRAX prediction model appears to be the best accepted model and estimates a 10-year risk of hip fracture for Mrs. Wilson to be 0.5%, (although 6.5% "major osteoporotic fracture") 13 When one adjusts weight parameters in the FRAX model, the patient could have up to a 2% 10-year risk of hip fracture. To convert from a 10 year risk, we assumed 1/3 to 2/3 of risk would be in the first 5 years.
Mrs. Wilson therefore has a 0.17%-1% risk of hip fracture in next 5 years b. What would you tell Mrs. Wilson is the chance that bisphosphonate therapy (e.g. alendronate) will prevent her from having a hip fracture in the next 5 years?
The Crandall & Shekelle systematic review provides a RR 0.6-0.8 for hip fracture if taking bisphosophonates. In other words, relative risk reduction was 20-40%. Given a 0.17%-1.0% risk of hip fracture over 5 years; the benefit would then be 0.1-0.4% 14 For comparison, the 2014 AIM Crandall & Shekelle article NNT ~80 over 1-3 years for alendronate for vertebral or non-vertebral fractures but provided no NNT for hip fracture alone. 14 Some have discussed there is no definite effect on hip fracture prevention. 15 Therefore, we conclude that Mrs. Wilson has a 0.17-1% risk of hip fracture in 5 years that will be decreased by 0-0.4% if she takes bisphosphonate therapy.

Do Guidelines recommend treatment?
USPSTF would not recommend screening this patient with DEXA "The U.S. Preventive Services Task Force (USPSTF) recommends screening for osteoporosis in women age 65 years and older, and in women younger than age 65 years who have been through menopause and are at increased risk for osteoporosis." 16 Consider Mr. Brown, a healthy 52-year-old man who is found to have a screening LDL of 150 and HDL of 40. He has tried lifestyle interventions, has no particular preference for treatment and wants your advice.
This is a case of primary prevention for mild hyperlipidemia.
To determine the probability of cardiovascular events in a patient with hyperlipidemia, we found clinical prediction scores to be the best validated method. Similar to question 1, experts noted the ASCVD risk calculator may overestimate risk, so we included a range of risk.
ACC ASCVD Risk Estimator plus 8 His 10-year risk varies by total cholesterol which is dependent on triglyceride level, which we did not provide. We are therefore providing a range of correct answers: If total cholesterol = 190, then 10-year risk 4.4% (TGL 0) If total cholesterol = 300, then 10-year risk 7.9% (TGL 550) Assuming 1/3 to 2/3 of that risk is in the first 5 years 1.5% to 5.3% This risk estimate is similar to ACC/AHA guidelines. 18,19 a. How likely is Mr. Brown to have a cardiovascular event within 5 years with no additional treatment? 1.5%-5.3% c. What would you tell Mr. Brown is the chance that moderate-intensity statin therapy will prevent him from having a cardiovascular event in the next 5 years?
Relative benefit of statins based on the American Heart Journal: all major CV events RR: 0.74, 95%CI: 0.67-0.81 (19%-33% relative risk reduction) 20 Similarly, the ASCVD Risk estimator uses 25.2% relative risk for all ranges of recommended treatment.