ASPIRE CLASS 6: Interpreting Results and Writing an Abstract Jordan King, PharmD, MS

Interpreting Results Explain the difference between cumulative incidence, incidence rate, and prevalence Explain the difference between relative risk, odds ratio, and hazard ratio Calculate the number needed to treat and the number needed to harm

COMPARISON OF UPPER GASTROINTESTINAL TOXICITY OF ROFECOXIB AND NAPROXEN IN PATIENTS WITH RHEUMATOID ARTHRITIS Bombardier C, et al. N Engl J Med 2000;343:1520-8. Design: Randomized, double-blind, active-control Intervention: 50 mg of rofecoxib daily vs 500 mg of naproxen twice daily Primary Outcomes: Efficacy – confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers) Safety – mortality, ischemic cerebrovascular events, myocardial infarctions

Measures of disease frequency (measures the occurrence of illness) Incidence (occurrence of disease) Rate or proportion Prevalence (disease status) Measures of association (comparisons between two or more interventions) Relative (ratio) Absolute (difference)

Incidence proportion (risk)  

Calculating risk Rofecoxib Naproxen Outcome N total N with Event GI 4047 56 4029 121 MI 17 4           Bombardier C, et al. N Engl J Med 2000;343:1520-8. Curfman G, et al. N Engl J Med 2005;353:2813-4.

Incidence rate  

Calculating incidence rate Rofecoxib Naproxen Outcome N total N with Event Person-years at risk GI 4047 56 2667 4029 121 2689 MI 17 2315 4 2316           Bombardier C, et al. N Engl J Med 2000;343:1520-8. Curfman G, et al. N Engl J Med 2005;353:2813-4.

Prevalence  

Prevalence Characteristic Rofecoxib group Naproxen group Age, years 58±9 58±10 Female sex 79.6% 79.8% Etc…

Measures of association Used to help us determine differences in effect between exposures Calculated from the measures of disease frequency Can be absolute or relative Absolute = difference (subtract) Relative = ratio (divide)

Relative Measures Ratio of risk or rates Calculated as RR = Risk1/Risk2 Interpretation: relative effect = RR – 1 RR = 1.4%/3.0% = 0.47 Relative effect = 1 – 0.47 = 0.53; there is a 53% relative reduction in the risk of a GI event in the rofecoxib group compared to the naproxen group Null = 1 Rofecoxib Naproxen Outcome Absolute Risk (AR) Incidence Rate (IR) Relative Risk Incidence Rate Ratio GI 1.4% 2.1 3.0% 4.5 0.47 MI 0.42% 7.3 0.10% 1.7 4.20 4.29

Absolute Measures The difference in the risk (probability of event) or rate between two groups Calculated as Risk1 – Risk2 Interpretation: ARD = 1.4% - 3.0% = -1.6% there is a 1.6% absolute reduction in the risk of a GI event in the rofecoxib group compared to the naproxen group Null = 0 Rofecoxib Naproxen Outcome Absolute Risk (AR) Incidence Rate (IR) Absolute Risk Difference Incidence Rate Difference GI 1.4% 2.1 3.0% 4.5 -1.6 -2.4 MI 0.42% 7.3 0.10% 1.7 0.32 5.6 Time endpoint is 60 minutes

Number Needed to Treat (NNT) & Number Needed to Harm (NNH) The average number of patients who need to be treated to prevent (or cause) one additional event Calculated from absolute differences 1/ARD Interpretation: NNT = 1 / (0.014 - 0.030) = 62.5; on average, 63 patients would need to receive rofecoxib, as opposed to naproxen, to prevent one additional GI event NNH = 1 / (0.0042 - 0.0010) = 312.5; on average, 313 patients would need to receive rofecoxib, as opposed to naproxen, to cause one additional MI TIME!

Interpreting and presenting the results (Efficacy) From the abstract: “During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001).” What was the measure of disease frequency? What was the measure of association? What was the reference group? How do we interpret these values? Bombardier C, et al. N Engl J Med 2000;343:1520-8.

Interpreting and presenting the results (Safety) From the abstract: “The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7)” What was the measure of disease frequency? What was the measure of association? What was the reference group? How do we interpret these values? Bombardier C, et al. N Engl J Med 2000;343:1520-8.

Other measures of effect Hazard ratio (HR) Used for time to event analysis Calculated from a Cox Proportional Hazards model Commonly combined with Kaplan-Meier curves and statistics Ratio of hazard rates (relative measure) Hazard h(t) is different than Survival S(t) You don’t need to worry about this How often a particular event happens in one group compared to how often it happens in another group, over time Null = 1

Other measures of effect  

Calculating Odds Ratios GI event MI Yes No Group Rofecoxib 56 (a) 3991 (b) 17 (a) 4030 (b) Naproxen 121 (c) 3908 (d) 4 (c) 4025 (d)    

Writing an Abstract List the essential elements of an abstract Recognize and apply succinct writing to an abstract

Tips for writing a conference abstract Start with the conference writing guide! Provide only main objectives, methods, results, and conclusions Space is very limited (you can use abbreviations to save characters, but limit number) Do not list results that are not stated in the methods Statistics used is optional - I typically describe statistic used to assess primary outcome (e.g., Cox proportional hazards models were used to ….) Give just enough information in the abstract to make the reviewers interested in hearing more A reviewer will be unable to evaluate the quality of the research from an abstract alone Flow is very important Abstract must be stand alone

Other thoughts Think about best audience when choosing where to submit Conference Poster session within conference Key words are sometimes made up by you and sometimes chosen from a list provided by the conference Acceptance rates vary greatly between conferences Don’t worry about a rejection Consider timing of manuscript submission and embargo policies Very rare to submit an abstract with results pending now that you are not a student (most conferences will not accept and I don’t recommend) Posters last a minute, manuscripts are forever