Operations Subcommittee Report and Follow-up Retention Insights

MESA Operations

Operations Subcommittee Report 1. Timeline 2. Follow-up calls 3. Participant Relations Committee 4. Exam 6 Core and Ancillary Study Progress Alerts Results Reporting 5. Retention Strategies

MESA 3 Timeline Exam 6 Sept 6, 2016 March 30, 2018 Annual Follow-up phone calls run congruent with fiscal years

Follow-up Call Retention 100% 90% 85% 80% 70% 60% 50% 40% 30% 20% 10% 0% FU1 FU2 FU3 FU4 FU5 FU6 FU7 FU8 FU9 FU10 FU11 FU12 FU13 FU14 FU15 FU16 FU17 FU18 Done Retention = Completed / (Enrolled Dead)

Follow-up Retention by Ethnicity All Sites 100 90 85% 80 Retention Rate White A-A 70 Hisp. Chin. 60 50 40 FU9 FU10 FU11 FU12 FU13 FU14 FU15 FU16 FU17 FU18 Retention = Completed / (Enrolled Dead) except FU 15 (windowed)

Follow-up 18 Completion by Site Follow- up Due 831 900 854 877 969 1080 5511 Interviews Completed 495 508 634 664 642 635 3578 Site Name Contacts Made Unable Refused Wake Forest Columbia Hopkins Minnesota NWU UCLA Total 536 551 708 719 719 800 4033 65% 61% 83% 82% 74% 74% 73% 60% 56% 74% 76% 66% 59% 65% 31 38 64 53 64 147 397 9 2 6 1 11 15 44 Includes active and study drop out participants with closed contact windows for true retention.

Follow-up Retention by Site WFU Columbia JHU 100 100 100 90 90 90 85% 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 NWU UCLA Minnesota 100 100 100 85% 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 Retention = Completed / (Enrolled Dead) except FU 18 (windowed)

Follow-up FU18 Ended August 14, 2017 (65% complete) Scheduled Exam 6 and asks participants stroke symptom and medical literacy questions. FU19 started August 15, 2017 Adds questions to assess cognitive impairment, continues with Exam 6 scheduling for those who have not completed Exam 6.

Participant Relations Committee Newsletter Mailed in August 2017 Articles include Exam 6 Update and invitation (Lorraine Silsbee) Combatting Alzheimer s Disease (Tim Hughes) Seeking Clues to Early Heart Failure (Alain Bertoni) One newsletter per year planned for remainder of MESA 3 contract

Exam 6 Completion 4500 4000 3500 3000 2500 2000 1500 1000 500 0 10/13/2016 10/26/2016 11/21/2016 12/17/2016 12/30/2016 10/12/2017 10/25/2017 11/20/2017 12/16/2017 12/29/2017 3/18/2017 5/22/2017 7/26/2017 9/29/2017 12/3/2017 9/17/2016 9/30/2016 11/8/2016 12/4/2016 1/12/2017 1/25/2017 2/20/2017 3/31/2017 4/13/2017 4/26/2017 6/17/2017 6/30/2017 7/13/2017 8/21/2017 9/16/2017 11/7/2017 1/11/2018 1/24/2018 2/19/2018 9/4/2016 2/7/2017 3/5/2017 5/9/2017 6/4/2017 8/8/2017 9/3/2017 2/6/2018 Cumulative Count Cumulative Target As of 8/28/2017, 2400 participants completed Exam 6 core exam during the 245 clinic days (9.0 ppts/day). If on target, 2700 participants would have completed the exam (~11 ppts/day), so retention is currently at 89% of the target.

Exam 6 Completion WakeForest Completed 258 Exam 6 visits (1.1 per clinic day, 59% of goal). Target is 438 (1.8 per clinic day). Columbia Completed 345 Exam 6 visits (1.4 per clinic day, 72% of goal). Target is 478 (2.0 per clinic day).

Exam 6 Completion Johns Hopkins Completed 352 Exam 6 visits (1.4 per clinic day, 94% of goal). Target is 385 (1.6 per clinic day). Minnesota Completed 495 Exam 6 visits (2.0 per clinic day, 106% of goal). Target is 465 (1.9 per clinic day).

Exam 6 Completion Northwestern Completed 516 Exam 6 visits (2.1 per clinic day, 100% of goal). Target is 518 (2.1 per clinic day). UCLA Completed 434 Exam 6 visits (1.8 per clinic day, 93% of goal). Target is 465 (1.9 per clinic day).

Exam 6 Core Completion Blood Pressure 257 344 353 495 519 432 2400 Anthro pometry 259 344 353 495 519 433 2403 Medical History 260 343 353 494 516 431 2397 Personal History 259 340 353 494 513 430 2389 Physical Function 259 339 353 493 512 430 2386 Site WFU COL JHU MN NWU UCLA Total Visits Oximetry Phlebotomy Urine Medications 260 345 353 495 519 435 2407 257 342 352 495 519 432 2397 246 316 346 485 503 418 2314 247 308 334 487 510 426 2312 257 343 353 494 517 432 2396

Exam 6 AS Completion AFib Selected HR Monitor 260 345 353 495 519 435 2407 Consented HR Monitor Consented to Cog Function Tests Consented to Brain MRI Site WFU COL JHU MN NWU UCLA Total 161 194 194 277 253 269 1348 259 193 337 298 252 273 1612 162 189 192 291 252 271 1357 # with prior Afib (including E6 self- report) 18 23 23 27 31 34 156 Patch #2 Mailed to Ppt* Cog Function Testing Complete Eligible for Patch Patch #1 Applied Site # Alerts WFU COL JHU MN NWU UCLA Total 147 164 144 249 232 237 1173 122 130 138 222 205 233 1050 83 90 107 191 131 45 647 121 126 136 221 201 231 1036 5 3 4 5 10 10 37 *As of 8/24/2017, participants are asked to wear 1 heart monitor patch instead of 2.

Exam 6 AS Completion Heart Failure Arterial Stiffness Physical Activity 6MW Exclusion Site Selected Echo KCCQ-12 6MW WFU COL JHU MN NWU UCLA Total 122 124 131 221 201 224 1023 83 87 107 191 130 45 643 121 121 130 220 197 222 1011 18 21 23 27 29 33 151 5 3 4 5 10 10 37 122 124 131 221 201 224 1023 83 87 107 191 130 45 643

Exam 6 AS Completion UKNOW ICIQ- FLUTS/MLUTS Site Selected WFU COL JHU MN NWU UCLA Total 260 345 353 495 519 435 2407 259 338 352 494 512 430 2385

Exam 6 AS Completion MESA Memory Target sample (n=550, 80% of 675) for cognitive testing, MRI and AB-PET. LP sub-study has a target sample size of 200 (37% of 540)

Exam 6 AS Completion MESA Lung/Lung NS Lung/Lung NS Components Selected ANY Lung CT Consented ANY Lung CT Completed ANY Lung CT Selected Contrast CT Consented Contrast CT Completed Contrast CT Not eligible for Contrast Consented to Spirometry Completed Spirometry Completed Lung Q Site WFU COL JHU MN NWU UCLA Total 236 306 330 482 479 400 2233 232 283 309 462 360 388 2034 97 230 302 430 307 110 1476 140 215 235 175 381 315 1461 124 136 152 144 206 265 1027 39 75 113 100 115 46 488 14 34 27 39 79 24 217 96 228 299 427 305 110 1465 84 209 279 395 267 106 1340 95 228 302 430 307 110 1472 Spirometry Completion Completed Lung Questionna ire 189 254 301 437 380 346 1907 Selected for Spirometry Consented to Spirometry Completed Pre-BD Spirometry Not eligible for Pre-BD Spirometry Selected Post-BD Spirometry Completed Post-BD Spirometry Post-BD Spirometry Not Complete Exam 6 Visits Site Pre-BD Spiro not complete 50 92 99 98 97 88 524 WFU COL JHU MN NWU UCLA Total 260 345 353 495 519 435 2407 236 306 330 482 479 400 2233 234 291 324 475 463 393 2180 192 255 301 437 380 349 1914 12 11 15 15 17 11 81 30 25 8 23 66 33 185 32 68 71 32 39 43 285 18 24 28 66 58 45 239

Exam 6 AS Completion MESA INVITE Total Screeners Complete E6 Complete after INVITE start Study Drug Status for those consented Consent status for those eligible E6 Complete before INVITE start Screening Result E6 Pending 6A Visit Comple te 2-week phone call Not Eligible Incomplete Consented Dispensed Dispensed Complete Complete Complete E6 Visits E6 Visits complete Declined Screener Screener Screener Missing/ Selected Refused Consent Consent Pending Eligible E6 not Not Site 5 0 707 736 631 816 2890 145 147 91 223 606 2 86 148 213 249 696 60 132 213 247 652 476 441 327 344 1588 0 0 9 0 9 22 36 79 57 194 15 53 109 143 320 25 62 80 58 225 26 14 0 2 42 23 55 63 54 195 2 2 0 4 8 0 5 16 52 63 54 185 7 3 0 0 10 WFU COL JHU NWU Total 52 56 48 161 19 29 20 68 17 43 11 73 17 0 22 Of 739 screened participants, 31% are eligible, 44% ineligible, and 26% refused to participate. 85% of ineligible participants were excluded for exceeding 1000IU of vitamin D daily.

Exam 6 AS Completion Epigenetics of Atherosclerosis CUS Site Consented Selected and had E6 Visit Completed CUS CUS not completed WFU COL JHU MINN Total 3 1 1 1 6 207 298 250 345 1100 161 189 184 273 807 41 137 175 194 547

Exam 6 RC Data Transmission Echo WF U 177 172 5 Col. JHU UMN NWU UCLA Total Echo Completed Data Received at CC Data Not Received at CC No data for HT letter after 8 weeks No data for HT letter after 12 weeks 339 316 23 340 324 16 462 443 19 513 497 16 421 401 20 2252 2153 99 0 0 0 1 0 1 2 0 0 0 1 0 0 1

Exam 6 RC Data Transmission Heart Monitor Patch WFU 209 202 196 6 3 Col. 211 192 179 13 3 JHU 220 216 197 19 1 UMN 407 396 386 10 1 NWU 332 318 299 19 9 UCLA 289 269 258 11 16 Total 1668 1593 1515 78 33 Heart Monitor Patch Registered (1 or 2 per ppt) Patches Received at RC Data Received at CC (# patches) Data Not Received at CC (# patches) No data for HT letter after 8 weeks (requires data from 2 patches) No data for HT letter after 12 weeks (requires data from 2 patches) 13 19 29 41 24 133 269

Exam 6 RC Data Transmission Spirometry WF U 192 179 13 5 1 Col. JHU UM N 437 372 65 32 26 NWU UCL A 349 239 110 0 96 Total Spirometry Completed Data Received at CC Data Not Received at CC No data for HT Letter after 8 weeks No data for HT Letter after 12 weeks 255 235 20 3 6 301 283 18 0 0 380 368 12 1 8 1914 1676 238 41 137

Exam 6 RC Data Transmission Blood Assays WF U 246 225 21 0 0 Col. JHU UMN NWU UCL A 418 370 48 0 0 Total Phlebotomy Completed Lipid Data Received at CC Data Not Received at CC No data for Lab Letter after 8 weeks No data for Lab Letter after 12 weeks 316 294 22 1 0 346 324 22 0 0 485 461 24 0 0 503 478 25 0 0 2314 2152 162 1 0

Exam 6 RC Data Transmission Lung CT Emphysema WF U 82 72 Col. JHU UMN NWU UCLA Total Lung CT Completed Data for High-Tech Letter Received at CC Data for High-Tech Letter Not Received at CC No data for HT letter - scan performed 4<8 weeks prior No data for HT letter - scan performed 8<12 weeks prior No data for HT letter scan performed > 12 weeks prior 204 165 276 251 389 346 307 276 78 59 1333 1169 88% 81% 91% 89% 90% 76% 88% 10 39 25 43 31 19 167 2 24 1 10 5 1 43 0 3 12 2 4 1 22

Exam 6 Alerts Site Oximetry Complete Oximetry Alert BP Complete BP Alert Echo Complete Echo Read Complete Echo Alerts Participants with 1st Heart Monitor Patch Applied Heart Monitor Patch Safety Read Complete (2 per ppt) Heart Monitor Patch Alert CT Complete Lung Safety Read Done Lung CT Alerts* Lipids Data Received Lipids Alert Carotid US Complete Carotid US Alerts Wake 257 0 257 2 174 187 0 122 Col 342 4 344 4 336 298 9 84 JHU 352 2 353 16 321 314 4 129 Minn 495 1 495 9 461 433 5 211 NWU 519 1 519 9 507 483 5 201 UCLA 433 1 433 5 375 405 8 216 Total 2398 9 2401 45 2174 2120 31 963 194 176 195 383 296 255 1499 6 97 81 4 225 1 41 5 6 230 187 13 294 3 138 11 6 302 282 38* 324 1 175 9 7 430 384 32 461 2 195 15 11 307 290 78* 478 3 0 0 10 113 82 10 370 3 0 0 46 1479 1306 175 2152 13 549 40

Exam 6 Results Reporting Lab Assays 25th Percentile 75th Percentile Procedure Count Minimum Median Maximum 3: Wake Forest 4: Columbia 5: Johns Hopkins 6: Minnesota 7: Northwestern 8: UCLA Total 203 277 305 435 450 358 2028 18 13 17 16 3 4 3 28 27 27 26 25 23 28 33 34 34 32 31 29 32 41 49 45 42 42 36 42 155 173 94 94 148 67 173

Exam 6 Results Reporting Spirometry 25th Percentile 75th Percentile Procedure Count Minimum Median Maximum All Sites 3: Wake Forest 4: Columbia 5: Johns Hopkins 6: Minnesota 7: Northwestern 8: UCLA 1357 167 205 270 320 332 63 2 12 12 3 2 26 20 46 41 47 40 48 46 61 56 54 57 50 56 57 71 69 67 71 63 68 72 92 301 235 246 143 301 183 244

Exam 6 Results Reporting Echo 25th Percentile 75th Percentile Procedure Count Minimum Median Maximum All Sites 3: Wake Forest 4: Columbia 5: Johns Hopkins 6: Minnesota 7: Northwestern 8: UCLA 2018 171 296 312 409 473 357 12 14 12 12 18 14 19 49 51 49 43 50 45 56 62 64 61 54 62 58 66 76 77 76 70 75 72 80 320 112 320 196 218 175 162

Exam 6 Results Reporting Heart Patch Monitor 25th Percentile 75th Percentile Procedure Count Minimum Median Maximum All Sites 3: Wake Forest 4: Columbia 5: Johns Hopkins 6: Minnesota 7: Northwestern 8: UCLA 539 84 47 74 155 149 30 14 14 34 34 35 39 62 64 70 68 58 61 68 79 85 128 103 73 73 91 90 129 184 149 104 97 147 167 317 247 317 306 287 287 227

Retention Strategies Home Visits (starting September 2017) Limited one hour exam with core components Invitation to Exam 6 for study dropouts Exam 6 announcements and site-specific Ancillary Study descriptions in MESA Messenger Newsletter