The survey yielded a total of 435 responses. After removing duplicates and cleaning the data set, a total of 355 responses from 24 countries were included in the analysis. Table 2 highlights the distribution of participants by site type, therapeutic areas of focus, region, site setting, and role. More than half of respondents represented a government-affiliated, not-for-profit clinic, hospital, or health system (180/355; 50.7%). Most respondents resided in North America (169/247; 68.4%) and Europe (61/247; 24.7%). Most sites represented by participants were located in an urban setting (169/247; 67.5%). A majority of respondents self-identified as being a principal investigator or sub-investigator (149/238; 62.6%). The sample included a broad mix of sites by therapeutic area of focus with the two largest areas being oncology (13.0%) and cardiovascular diseases (11.5%). Other areas of focus included neurology (7.6%), hematology (7.4%), psychiatry/psychology (4.7%), trauma (4.0%), internal medicine (3.8%), pediatrics/neonatology (3.8%), infectious diseases (3.6%), endocrinology (3.4%), and “other” areas (37.2%). See Table 2.
---Insert Table 2---
Table 2: Description of Survey Data Collected
|
N
|
%
|
Site Type
|
|
|
Government-affiliated, not-for-profit clinic, hospital, or health system
|
180
|
50.7%
|
For profit clinic, hospital or health system
|
79
|
22.3%
|
Stand-alone, dedicated research site (or equivalent)
|
41
|
11.5%
|
Part of an investigative site network (SMO, IRO, or equivalent)
|
12
|
3.4%
|
Other
|
43
|
12.1%
|
Total
|
355
|
100.0%
|
Therapeutic Areas of Focus at Site*
|
|
|
Oncology
|
69
|
13.0%
|
Cardiovascular and Circulatory Diseases
|
61
|
11.5%
|
Neurology
|
40
|
7.6%
|
Hematology
|
39
|
7.4%
|
Psychiatry/Psychology
|
25
|
4.7%
|
Trauma
|
21
|
4.0%
|
Internal Medicine
|
20
|
3.8%
|
Pediatrics/Neonatology
|
20
|
3.8%
|
Infections and Infectious Diseases
|
19
|
3.6%
|
Endocrinology
|
18
|
3.4%
|
Other**
|
197
|
37.2%
|
Total
|
529
|
100.0%
|
Region***
|
|
|
North America
|
169
|
68.4%
|
Europe
|
61
|
24.7%
|
APAC
|
17
|
6.9%
|
Total
|
247
|
100.0%
|
Site Setting
|
|
|
Urban
|
164
|
67.5%
|
Suburban & Rural
|
79
|
32.5%
|
Total
|
243
|
100.0%
|
Role
|
|
|
Principal Investigator (PI) or Sub-Investigator (Sub-I)
|
149
|
62.6%
|
Site Director, Research Manager, or Equivalent
|
20
|
8.4%
|
Clinical Research Coordinator (CRC) or Study Coordinator (SC)
|
16
|
6.7%
|
Clinical Research Assistant, or Equivalent
|
12
|
5.0%
|
Ethical Review Board - ERB (director/coordinator)
|
6
|
2.5%
|
Clinical Research Nurse Coordinator (CRNC) or Clinical Research Nurse (CRN)
|
5
|
2.1%
|
Other
|
30
|
12.6%
|
Total
|
238
|
100.0%
|
*Respondents were asked to select all therapeutic areas of focus at their site. Many selected more than one area. The number of site respondents providing therapeutic area of focus data was 248.
**Ophthalmology, Dermatology, Obstetrics/Gynecology, Pulmonary/Respiratory Diseases, Gastroenterology, Rare Diseases and Disorders, Vaccines, Immunology, Genetic Disease, Rheumatology, Family Medicine, Gene Therapy, Orthopedics/Orthopedic Surgery, Musculoskeletal, Urology, Nephrology, Nutrition and Weight Loss, Plastic Surgery, Dental and Oral Health, Otolaryngology, Podiatry, Sleep.
***Countries represented in sample ordered by volume: United States, United Kingdom, Canada, Spain, Japan, Greece, Australia, Italy, Portugal, Croatia, China, Germany, Romania, Slovenia, Belgium, Bulgaria, Cyprus, Denmark, France, Ireland, Latvia, Oman, Slovakia, and Switzerland.
Perceptions of and Experience with DCTs
Based on the definitions provided in Table 1, 212 respondents shared their level of exposure to DCT technologies and services and the models within which the solutions were used. Half of respondents (50.5%; 107/212) reported having no experience with DCT (see Table 3). Approximately one in five respondents (46/212; 21.7%) only had experience participating in hybrid DCTs. Another one in five respondents (45/212; 21.2%) had experience with both fully decentralized and hybrid decentralized trials. And 6.6% (14/212) of respondents said they only had experience with fully decentralized trials.
---Insert Table 3---
Table 3: Extent of site personnel experience with DCTs
|
N
|
%
|
I don't have any experience with Decentralized Clinical Trials
|
107
|
50.5%
|
I only have experience with Hybrid Decentralized Clinical Trials (DCTs)
|
46
|
21.7%
|
I have experience with both Fully and Hybrid Decentralized Trials (DCTs)
|
45
|
21.2%
|
I only have experience with Fully Decentralized Clinical Trials (DCTs)
|
14
|
6.6%
|
Total
|
212
|
100.0%
|
Table 4 shows general investigative site perceptions of the overall burden associated with performing DCT-supported clinical trials: half (50.6%; 39/77) reported that DCTs are “more” or “much more” burdensome compared to traditional clinical trials; 31.2% (24/77) indicated that DCTs are “less” or “much less” burdensome than traditional clinical trials; and 18.2% indicated that, overall, they found little to no difference between each of these approaches.
---Insert Table 4---
Table 4: Perceived burden of DCTs compared to Traditional Clinical Trials
Burden: DCTs versus Traditional Trials
|
N
|
%
|
DCTs are a 'more' or 'much more' burdensome than traditional trials
|
39
|
50.6%
|
DCTs are a 'little less' or 'much less' burdensome than traditional trials
|
24
|
31.2%
|
DCTs are 'no more or less' burdensome than traditional trials
|
14
|
18.2%
|
Total
|
77
|
100.0%
|
More than half of participants (55.7%; 41/75) prefer a hybrid clinical trial implementation model (as defined in Table 1). However, a substantial proportion of respondents still prefer the traditional clinical trial implementation model (24.0%; 18/75). See Table 5.
---Insert Table 5---
Table 5: Preferred Clinical Trial Model at Sites
Preferred Clinical Trial Model
|
N
|
%
|
Hybrid Decentralized Clinical Trial
|
41
|
54.7%
|
Traditional Clinical Trial
|
18
|
24.0%
|
No preference
|
11
|
14.7%
|
Fully Decentralized Clinical Trial
|
5
|
6.7%
|
Total
|
75
|
100.0%
|
Respondents also provided their assessment of investigative site staff experience required to successfully carry out traditional and decentralized approaches (as defined in Table 1). More than half of respondents (51.9%; 40/77) indicated that DCT solutions and approaches require “somewhat more” or “significantly more” experienced staff compared to a traditional clinical trial. See Table 6.
---Insert Table 6---
Table 6: Site Personnel Experience Required for DCT Implementation
Staff Experience Requirements
|
N
|
%
|
A DCT requires 'somewhat more' or 'significantly more' experienced staff compared to a traditional trial
|
40
|
51.9%
|
Both trial implementation models require the same level of staff experience
|
28
|
36.0%
|
A traditional trial requires 'somewhat more' or 'significantly more' experienced staff compared to a DCT
|
9
|
11.7%
|
Total
|
77
|
100.0%
|
In the aggregate, combining all areas where traditional and DCT-supported clinical trials were compared, those involving DCT solutions increased protocol execution burden by 10.4% (Refer to Table 7). This estimate includes the incremental burden associated with DCT solutions when educating patients about study procedures and equipment (25.3%); use of new technologies and devices (24.54%); adverse event monitoring and reporting (19.7%); reporting protocol deviations (18.33%); drug dispensing and shipping (17.8%); trial kit dispensing (13.3%); meeting regulatory requirements (13.2%); record keeping (10.6%); and storing clinical trial kits and materials (6.2%). Drug storage was the only procedure evaluated where a significant change was not observed (0.8% decrease). When asked to compare clinical trials involving investigative site visits, home nurse visits, and telehealth visits, investigative sites reported higher burden with in-home nurse visits (17.8% increase), and lower burden with telehealth patient visits (14.9% decrease). See Table 7.
---Insert Table 7---
Table 7: Overall Perceived Change in Burden: Traditional vs. Decentralized Approaches
|
N
|
Mean % Change
|
Std. Deviation
|
Percentage Change in Burden from Traditional Clinical Trial Model to DCT
|
|
|
|
Educating Patients About Study Procedures and Equipment
|
85
|
25.3
|
38.8
|
Requirement to Use New Technology and/or Devices
|
84
|
24.5
|
40.5
|
Adverse Event Monitoring and Reporting
|
79
|
19.7
|
38.8
|
Reporting Protocol Deviations
|
75
|
18.3
|
37.4
|
Drug Dispensing and Shipping
|
74
|
17.8
|
42.8
|
Trial Kit Dispense
|
73
|
13.3
|
44.1
|
Meeting Regulatory Requirements
|
72
|
13.2
|
43.8
|
Record Keeping
|
80
|
10.6
|
45.4
|
Storing Clinical Trial Kits and Materials
|
61
|
6.2
|
41.2
|
Drug Storage
|
54
|
-0.8
|
44.2
|
Overall Change in Burden Traditional vs. DCT
|
125
|
10.4
|
33.1
|
Percentage Change in Burden from In-person Visit at a Trial Site to In-home/Virtual
|
|
|
|
In-home Nurse Visits
|
83
|
17.8
|
57.3
|
Telehealth Patient Visits
|
104
|
-14.9
|
45.6
|
Note: Burden associated with visits (discrete tasks) are compared between in-person vs. site-based and are therefore presented separately. The upper section of the table compares continuous tasks on the basis of using digital versus analog approaches. The change in burden in all cases included in the table was evaluated on a scale from -100 to 100.
Table 8 shows the perceived burden of performing general management activities in DCT-supported clinical trials was only slightly higher (0.2%) compared to traditional models whereas the burden of performing training activities decreased slightly by 1.6%. In all, the perceived burden of performing most clinical trial management and operations activities—which typically require direct contact with the sponsor or clinical research organization—decreased significantly within a DCT implemenattion framework. The estimate of burden for general management activities within both a traditional clinical trial and DCT framework accounted for the following categories of activities: staff training activities, pre-activation and site initiation activities, patient recruitment and management activities, data management and trial closeout activities, and general clinical trial operations (e.g., invoicing and collections, regulatory compliance reporting, storing source documents).
The perceived burden of pre-activation and site initiation activities decreased by 20.2% within a DCT framework compared to using traditional approaches. Similarly, the perceived burden of patient recruitment, management, and retention activities decreased by 10.8% when using a DCT framework, as did both data management and closeout activities (a 15.1% decrease) and general site operating activities (a 15.8% decrease).
---Insert Table 8---
Table 8: Burden of Performing Clinical Trial Management and Operations Activities
MANAGEMENT AND OPERATIONS ACTIVITIES
|
Traditional Clinical Trial
|
Decentralized Clinical Trial (DCT)
|
% Change in Burden
|
N*
|
Mean Burden Score
|
Std. Deviation
|
N*
|
Mean Burden Score
|
Std. Deviation
|
General Management Activities
|
|
|
|
|
|
|
|
Contract Execution
|
61
|
64.1
|
20.2
|
61
|
62.3
|
23.6
|
-2.8%
|
Budget Preparation
|
67
|
62.3
|
19.5
|
67
|
61.8
|
19.2
|
-0.9%
|
Ethical Review Board Submission and Approval Process
|
59
|
61.9
|
19.3
|
63
|
60.9
|
23.9
|
-1.6%
|
Amendments/Changes to Contracts
|
59
|
61.2
|
21.3
|
60
|
59.3
|
22.0
|
-3.1%
|
Follow-up with Sponsor
|
61
|
57.5
|
19.2
|
65
|
55.0
|
23.2
|
-4.4%
|
Feasibility Assessment
|
73
|
56.0
|
17.6
|
76
|
57.8
|
18.7
|
3.2%
|
General Management Activities Total
|
380
|
60.0
|
15.7
|
392
|
60.1
|
18.4
|
0.2%
|
Training Activities
|
|
|
|
|
|
|
|
In Person Training
|
59
|
60.5
|
21.0
|
70
|
62.2
|
21.2
|
2.8%
|
Virtual Training
|
55
|
58.2
|
19.2
|
68
|
56.0
|
22.2
|
-3.8%
|
Training Activities Total
|
114
|
60.0
|
18.1
|
138
|
59.1
|
20.1
|
-1.6%
|
Pre-activation and Site Initiation Activities*
|
|
|
|
|
|
|
|
Investigator Meetings**
|
65
|
64.4
|
21.8
|
67
|
48.5
|
25.9
|
-24.7%
|
Site Initiation Visits (SIVs)
|
60
|
64.3
|
19.1
|
64
|
50.4
|
25.3
|
-21.7%
|
Pre-Study Visits
|
61
|
58.1
|
20.0
|
64
|
52.8
|
21.5
|
-9.1%
|
Pre-Activation or Site Initiation Activities Total
|
186
|
62.3
|
18.6
|
195
|
49.8
|
23.0
|
-20.2%
|
Patient Recruitment, Management, and Retention Activities
|
|
|
|
|
|
|
|
Patient Enrollment
|
58
|
63.1
|
16.8
|
57
|
59.2
|
22.5
|
-6.2%
|
Initial Outreach and Identification
|
55
|
62.7
|
19.5
|
62
|
57.8
|
20.8
|
-7.8%
|
Patient Screening
|
58
|
61.3
|
16.0
|
62
|
57.2
|
20.7
|
-6.8%
|
Scheduling Visits
|
52
|
58.6
|
18.3
|
64
|
50.5
|
21.1
|
-13.8%
|
Visit Reminders
|
49
|
51.2
|
17.3
|
60
|
46.2
|
22.4
|
-9.8%
|
Patient Recruitment, Management, and Retention Activities Total
|
272
|
60.1
|
15.0
|
305
|
53.6
|
18.8
|
-10.8%
|
Data Management and Closeout Activities
|
|
|
|
|
|
|
|
Merging Data from Various Sources
|
49
|
64.0
|
22.3
|
58
|
54.9
|
25.8
|
-14.1%
|
Data Entry
|
54
|
61.7
|
18.7
|
55
|
51.3
|
24.7
|
-16.9%
|
Cleaning Data
|
51
|
61.7
|
21.6
|
52
|
55.0
|
26.4
|
-11.0%
|
Query Handling
|
50
|
59.9
|
21.8
|
51
|
54.7
|
24.7
|
-8.7%
|
Source Data Archiving or Storing
|
48
|
59.9
|
22.0
|
52
|
46.7
|
25.7
|
-22.0%
|
Review of Study Results with Patients
|
44
|
56.9
|
19.6
|
50
|
48.3
|
24.9
|
-15.1%
|
Data Management and Closeout Activities Total
|
296
|
60.3
|
18.0
|
318
|
51.3
|
22.2
|
-14.8%
|
Site Operations Activities
|
|
|
|
|
|
|
|
Patient Follow Up
|
50
|
59.8
|
18.1
|
55
|
51.5
|
21.7
|
-13.9%
|
Completing Regulatory Compliance Reporting
|
47
|
59.0
|
19.0
|
49
|
51.9
|
24.5
|
-12.0%
|
Invoicing and Collections
|
47
|
58.7
|
19.5
|
50
|
52.3
|
22.9
|
-10.9%
|
Receiving Investigational Drug Supply
|
48
|
57.2
|
19.0
|
49
|
52.4
|
21.4
|
-8.3%
|
Storing Source Documents
|
50
|
56.4
|
19.7
|
51
|
45.3
|
23.4
|
-19.7%
|
Patient (Subject) Reimbursement
|
45
|
56.2
|
22.2
|
46
|
48.3
|
21.5
|
-14.1%
|
Receiving Clinical Trial Kits and Materials
|
46
|
55.8
|
18.8
|
48
|
54.5
|
21.1
|
-2.4%
|
Site Operations Activities Total
|
333
|
58.5
|
17.8
|
348
|
49.3
|
18.5
|
-15.8%
|
*N is the total number of ratings provided by site respondents.
**Traditional Clinical Trial Meetings (conducted in person at site) versus DCT Meetings (conducted virtually)
Note: Respondents rated the burden of performing activities within a Traditional Clinical Trial, on a scale of 0-100, compared to scheduling and ordering routine blood work (e.g., CBC procedure). The burden level of Scheduling and Ordering Routine Blood Work at Trial Site = 50. A score lower than 50 means the activity is less burdensome than scheduling and ordering routine blood work. A score higher than 50 means the activity is more burdensome than scheduling and ordering routine blood work. Then, they rated the burden associated with the same feasible activities within a DCT, on a scale of 0-100.
Overall, investigative sites perceive increased burden when common protocol procedures are performed outside of the usual clinical trial setting including medication administration, routine procedures, lab and blood procedures, non-invasive and invasive procedures, and imaging procedures (See Table 9). Comon protocol procedures typically require direct study team-patient interaction.
The perceived burden of administering medications at home by the patient was 3.3% higher than that administered at the clinical trial site. The perceived comparative burden of administering medication at a local clinic or at home with the assistance of a home-health professional was 9.5% and 10.7% higher respectively. The medication administration procedures included in this assesment are oral pill, oral liquid, auto-syringe, IV, and topical administration.
The perceived burden of performing routine procedures was incrementally higher when performed virtually or remotely. The following routine procedures were included in our assessment: eye exam, hearing exam, neurology exam, pap smear, physical exam, skin exam, neurology exam, mental health exam, breast exam, testicular exam, and pupil exam. On average, the perceived burden of performing these procedures at the patient’s home (when feasible) was 6.8% higher compared to those performed at the clinical trial site. The perceived burden of performing these procedures at a local clinic or at home by a home-health professional (when feasible) was 11.4% and 15.6% higher respectively.
The perceived burden of collecting lab and blood samples (for example, finger prick samples, nasal swabs, sperm samples, stool samples, blood samples, etc.) was higher than those collected at the clinical trial site. When these samples are collected by the patient at home (when feasible), the perceived burden increased by 7.9%; and increased by 9.2% when collected at a local site or clinic. When samples are collected by a home-health professional at the patient’s home (when feasible), the perceived burden increased by 10.7%.
The perceived burden of performing non-invasive procedures declined by 4.4% when performed by the patient at home (when feasible) compared to performing them at the clinical trial site. However, when these procedures are performed at a local site or clinic, or by a home-health professional at the patient’s home, the perceived burden increased slightly by 1.4% and 2.8% respectively. Examples of non-invasive procedures evaluated include motors skills tests, walking tests, exercise tests and pulmonary tests.
The perceived burden of performing invasive procedures—for example, a urethral catheter, apheresis, a bronchoscopy, a cardiac catheter, an endoscopy or colonoscopy —decreased slightly by 1.1% when performed at a local clinic. However, when performed at home by a home-health professional (when feasible), the perceived burden increased by 3.3%.
The perceived burden of performing imaging procedures decreased by 2.0% when performed by the patient at home using a device (when feasible). However, when performed at a local clinic, the perceived burden increased by 4.8%.
Finally, the perceived burden associated with completing brief questionnaires decreased significantly (by 14.5%) when completed by the patient at home compared to at the clinical trial site. However, the perceived burden of completing questionnaires increased by 5.7% when a home-health professional completed the task at the patient’s home.
---Insert Table 9---
Table 9: Burden Scores - Clinical Trial Procedures
CLINICAL TRIAL PROCEDURES
|
N*
|
Mean Burden Score
|
Std. Deviation
|
% Change in Burden from Administering at Trial Site
|
Medication Administration Procedures
|
|
|
|
|
Administration at Clinical Trial Site (average of all procedure types)
|
56
|
55.1
|
16.5
|
|
Administration by Patient at Home (average of all feasible procedure types)
|
58
|
56.8
|
19.8
|
3.3%
|
Administration at Local Site/Clinic (average of all feasible procedure types)
|
50
|
60.3
|
22.0
|
9.5%
|
Administration by Home Health Professional at Home (average of all feasible procedure types)
|
45
|
60.9
|
19.1
|
10.7%
|
Routine Procedures
|
|
|
|
|
Performed at Clinical Trial Site (average of all procedure types)
|
55
|
53.1
|
21.6
|
|
Performed by Patient at Home (average of all feasible procedure types)
|
49
|
56.7
|
21.8
|
6.8%
|
Performed at Local Site/Clinic (average of all feasible procedure types)
|
43
|
59.1
|
20.5
|
11.4%
|
Performed by Home Health Professional at Home (average of all feasible procedure types)
|
44
|
61.4
|
15.8
|
15.6%
|
Lab and Blood Procedures
|
|
|
|
|
Collected at Clinical Trial Site (average of all sample types)
|
50
|
53.9
|
20.2
|
|
Collected by Patient at Home (average of all feasible sample types)
|
48
|
58.2
|
21.6
|
7.9%
|
Collected at Local Site/Clinic (average of all feasible sample types)
|
44
|
58.9
|
21.4
|
9.2%
|
Collected by Home Health Professional at Home (average of all feasible sample types)
|
44
|
59.7
|
18.7
|
10.7%
|
Non-invasive Procedures
|
|
|
|
|
Performed at Clinical Trial Site (average of all procedure types)
|
47
|
56.3
|
19.0
|
|
Performed by Patient at Home (average of all feasible procedure types)
|
44
|
53.8
|
20.7
|
-4.4%
|
Performed at Local Site/Clinic (average of all feasible procedure types)
|
40
|
57.1
|
20.6
|
1.4%
|
Performed by Home Health Professional at Home (average of all feasible procedure types)
|
40
|
57.9
|
20.8
|
2.8%
|
Invasive Procedures
|
|
|
|
|
Performed at Clinical Trial Site (average of all procedures)
|
41
|
68.0
|
23.7
|
|
Performed at Local Site/Clinic (average of all feasible procedures)
|
42
|
67.3
|
23.0
|
-1.1%
|
Performed by Home Health Professional at Home (average of all feasible procedures)
|
38
|
70.3
|
23.3
|
3.3%
|
Imaging Procedures
|
|
|
|
|
Performed at Primary Clinical Trial Site (average of all procedures)
|
45
|
59.4
|
23.9
|
|
Performed by Patient at Home Using a Device (average of all feasible procedures)
|
34
|
58.2
|
23.7
|
-2.0%
|
Performed at Local Site/Clinic (average of all feasible procedures)
|
35
|
62.2
|
23.6
|
4.8%
|
10-minute Patient Questionnaires
|
|
|
|
|
Completed at Primary Clinical Trial Site
|
41
|
52.8
|
23.3
|
|
Completed by Patient at Home Using a Device such as a Tablet or Smartphone
|
49
|
45.1
|
22.3
|
-14.5%
|
Completed at Local Site/Clinic
|
40
|
52.0
|
21.9
|
-1.5%
|
Completed at Patient's Home by Home Health Professional
|
41
|
55.8
|
20.7
|
5.7%
|
*N is the total number of ratings provided by site respondents.
Note: Respondents provided an estimate of burden for their site when performing each procedure in their therapeutic area of focus at the investigative site. They also gave a burden estimate for general procedure types performed using a DCT alternative, all on a scale from 0 to 100. To accurately measure burden, respondents compared the burden of each procedure against a central reference point: Measuring and Recording Vitals at the trial site (50). A score lower than 50 means the procedure is less burdensome than measuring and recording vitals at a trial site. A score higher than 50 means the procedure is more burdensome compared to measuring and recording vitals at a site.
Methods to Support Successful Use of DCT Solutions by Investigative Sites
Many respondents indicated that increasing flexibility in the use of site-provided versus sponsor-provided tools is a method that may aid in improving DCT implementation (29.0%). Expanding budgets for sites (14.3%) and increasing patient technical support (12.5%) were also frequently cited as methods to support the successful execution of decentralized clinical trials.
---Insert Table 10---
Table 10: Methods to Improve DCT Implementation
Improving DCTs*
|
N
|
%
|
Increase Flexibility in Use of Site-provided vs. Sponsor-provided tools
|
79
|
29.0%
|
Expand Budgets for Sites
|
39
|
14.3%
|
Increase Patient (Subject) Tech Support
|
34
|
12.5%
|
Expand Training for Sites
|
27
|
9.9%
|
Increase Patient (Subject) Educational Support
|
27
|
9.9%
|
Expand Training for Patients (Subjects)
|
24
|
8.8%
|
Increase Patient (Subject) Financial Support
|
23
|
8.5%
|
Other
|
19
|
7.0%
|
Total Number of Ratings
|
272
|
100.0%
|
*Respondents could select multiple options. Methods are shown in order of most selected to least selected. The number of site respondents providing therapeutic area of focus data was 77.