**UNITED ST AT**  **ES ENVIRONMENT AL**  **PROTECTION A GENCY**  WA SHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES
**MEMORANDUM**
**SUBJECT** : In formation Collection Request (ICR) for the Human Studies Rule

Calculation of Burden and Cost **TO:** File **FROM:** Kelly

Sherman Human Research Ethics Reviewer Office of Pesticide Programs **DATE:** September 2, 2008

Burden Hours for Respondents EPA sent consultation questions about the burden and cost estimates to five respondents

– the Agricultural Handlers Exposure Task Force (AHETF), the Antimicrobial Exposure Assessment Task Force II (AEATF), Carroll

- Lo ye , I CR, Inc., and Gray son. These five organizations are experienced in submitting human subjects research to OPP, and are expected to make additional submissions over the next several ye ars. The consultation responses received from the se respondents indicated that EPA’s previous estimates of the burden and cost were too low. T o calculate new burden and cost estimates for this renewal ICR, EPA relied upon the estimates provided in the five consultation responses. EPA calculated a weighted average of the different responses, recognizing that some study types are more complicated and costl y to conduct than others. The respondent burden and cost estimates that appear in Table 1 in the ICR , for research involving intentional e xposure of human s ubjects , are the weighted average s of the values in Table A (burden hour estimates for agricultural handler studies, from the AHETF), Table B (burden hour estimates for antimicrobial exposure studies, from the AEATF), and Table C (burden hour estimates for insect repellant studies, average d from the responses received from Carroll

- Lo yeand IC R, Inc.). The weighted average was calculated b y multiplying the burden hour estimates that appear in Tables A, B, and C by the expected number of each type of study, and then dividing the sum of those productsby

the total number of studies of all ty pes expected per year. The expected number of studies per year was also determined from the consultation responses. The respondent burden and cost estimates th at appear in Table 2 in the IC R, for all o ther s ubmitted research with human s ubjects , are based on the consultation response from Joel Panara at Grayson . Mr. Panara is familiar with submitting completed study reports to EPA for pre
- rule research for which HSRB protocol review is n ot required , and his consultation response was based on his billing records for work performed on several studies to generate the reports necessary to meet the requirements of the rule
. Hourly Rates for Respondents Four of the five respondents indicat ed that the hourly rates used b y EPA for calculating the estimated costs are too low. In determining the rates, OPP uses a single source of data, the Bureau of Labor Statistics ’ National Industry

- Specific Occupational Employ ment and Wage Estimates , and se lects the appropriate occupational category
. Using the BLS data allows EPA to be consistent between across sectors and occupations. If OPP were to separately research wages for each I CR, the methodology in determining the wages would not be consistent an d the wage rates could not be compared between sectors and occupations. Some wages would be biased high, while others would be biased low. The BL S wages are categorized by North American Industry Classification Sy stem (NAI CS) codes , and therefore are ind ustry- specific. They

are, however, national averages. Therefore, some of the high wages earned by specialists in high cost localities are offset b y others who are less specialized in lower cost localities. The wage rates used in the draft ICR were fro m NAI CS 325300 (Pesticide, Fertilizer, and Other Agricultural Chemical Manufacturing). Upon reconsidering the possible NAI CS categories, EPA has concluded that NAICS 541710 is more appropriate because there are a variety of ty pes of scientists involved in the human studies I CR, with higher education requirements than in pesticide manufacturing companies. The wage rates in NAICS 541710 are slightl y high er than those in NAICS 325300, which helps to address the comments in the consultation responses indicating that the hourly rates used by the Agency

are too low. Agency Burden and Costs The estimated burden and costs to the Agency are derived from input from EPA staff members who have prepared reviews for studies that were presented to the HSRB. Recognizing that some study types are more complicated and time consuming to review that others, EPA calculated a weighted average using the staff time estimates and the expected frequency

of receiving different ty

pes of studies. The values calculated based on the staff input appear in Tables E, F, and G. The weighted averages are provided in ICR Tables 3 and 4. Number of TransactionsThe estimated number of transactions is based heavily on the consultation responses from the five respondents, as well as EPA’ s historical experience and knowledge of upcoming submissions.

**RESPONDENT BURDEN HOUR ESTIMATES**
**Table A. Ag**  **ricultural Handler Exposure Studies** 

**– Burden Hour**  **Estimates from**  **AHETF’s Consultation Response Activities**  **Average Burden Hours Per Occurrence**  **Total Per Response**  **Management $138**  **Technical**

**$73 Clerical** 

**$42 Hours**  **Cost**

**($)** Rule familiarization and training 1 2 2 2 6 506 Prepare and submit protocol for IRB review 2 5 80 10 95 6,950 Prepare and submit protocol for EPA and HSRB review 3 15 240 26 276 20,682 Document ethical conduct of a completed study for which EPA and the HSRB have reviewed the protocol 4 10 260 10 285 20,780 Store, file, and maintain records 5 0 2 0 2 48,918

1 Values taken from table titled “Calculation of IPC per Human Study Based on AHETF Experience” in the AHETF’s follow

- up consultation response submission, sent via email from David Johns on to Kelly Sherman on 8

- 15
- 08. 2 Values taken from table titled “Calculation of IPC per Human Study Based on AHETF Experience” in the AHETF’s follow

- up consultation response submission, sent via email from David Johnson to Kelly Sherman on 8

- 15
- 08. 3 Values taken from table titled “Calculation of IPC per Human Study Based on AHETF Experience” in the AHETF’s follow

- up consultation response submission, sent via email from David Johnson to Kelly Sherman on 8

- 15
- 08. 4 Values taken from table titled “Table 1: Respondent Burden Estimates: Unit Costs of Discrete Activities Required by the Ne w Rule” from the AHETF’s original consultation response submission. The AHETF’s values, which were provided “per scenario” rather than “per study,” were divided by five to obtain per study amounts. 5 Values taken from table titled “Calculation of IPC per Human Study Based on AHETF Experience” in the AHETF’s follow

- up consultation response submission, sent via email from David Johnson to Kelly Sherman on 8

- 15
- 08.**Table B. Antimicrobial Exposure Studies** 

**– Burden Hour Estimates**  **from AEATF’s** 

**Consultation Response, with the adjustment described in footnote 1 Activities**  **Average Burden Hours Per Occurrence**  **Total Per Response**  **Management $138**  **Technical**

**$73 Clerical** 

**$42 Hours**  **Cost**

**($)** Rule familiarization and training 6 2 2 2 6 506 Prepare and submit protocol for IRB review 24 120 40 184 13,752 Prepare and submit protocol for EPA and HSRB review 40 320 40 400 30,560 Document ethical conduct of a completed study for which EPA and the HSRB have reviewed the protocol 24 80 24 148 10,160 Store, file, and maintain records 8 16 16 40 2,944

6 For the activity “Rule Familiarization and Training,” the AEATF estimated 12 management hours, 32 technical hours, and 8 clerical hours, based on expected personnel turnover. Time spent training new staff is not properly attributed to the paperwork and recordkeeping burdens of the rule. This is a one

- time activity. Since the AEATF is familiar with the rule, its costs for this activity should be small. Instead of using AEATF’s reported numbers, KS used the numbers reported by the AHETF (2 hrs. for each category).**Table C. Insect Repellant Studies** 

**– Burden Hour Estimates**  **from an Average of the** 

**Consultation Responses from Carroll -**  **Loye and ICR, Inc., with the adjustment described in footnote 2**  **Activities Average Burden Hours Per**  **Occurrence Total Per**  **Response Management**  **$138 Technical** 

**$73 Clerical** 

**$42 Hours**  **Cost**

**($)** Rule familiarization and training 7 1 1 1 3 253 Prepare and submit protocol for IRB review 54 54 24 132 12,402 Prepare and submit protocol for EPA and HSRB review 20 27 42 89 6,495 Document ethical conduct of a completed study for which EPA and the HSRB have reviewed the protocol 20 42 26 88 6,918 Store, file, and maintain records 3 6 1 1 0 894

**Table D. Documentation of Ethical Co**  **nduct of a Completed Study for w**  **hich EPA and HSRB have NOT reviewed the Protocol (per requirements at §26.1303)** 

**– Burden Hour Estimate**  **s Based on Consultation Response from Joel Panara at**  **Grayson (a laboratory with experience with submitting this type of info) Activities**  **Average Burden Hours Per Occurrence**  **Total Per Response**  **Management $138**  **Technical**

**$73 Clerical** 

**$42 Hours**  **Cost**

**($)** Document ethical conduct of a completed study for which EPA and the HSRB have not reviewed the protocol 5 16 8 29 2,194

7 For the activity “Rule Familiarization and Training,” Carroll

- Lo ye estimated 50 management hours, 100 technical hours, and 10 clerical hours. This is a one

- time activity, and since Carroll

- Lo ye is familiar with the rule, its costs for this activity shoul d be small. Thus, instead of using an average of Carroll

- Lo ye’s and ICR, Inc.’s numbers, OPP used only the numbers provided by ICR, Inc. for this activity.**For ICR Table 1** 

**Weighted Average Burden and Cost Estimates for Respondents** 

**– Research** 

**Involving Intentional Exposure of Human Subjects Activities**  **Average Burden Hours Per Response**  **Total Per Response**  **Management $138**  **Technical**

**$73 Clerical** 

**$42 Hours**  **Cost**

**($)** Rule familiarization and training 8 2 4 2 8 652 Prepare and submit protocol for IRB review 31 83 33 147 11,723 Prepare and submit protocol for EPA and HSRB review 25 181 37 243 18, 217 Document ethical conduct of a completed study for which EPA and the HSRB have reviewed the protocol 19 113 21 153 11, 753 Document ethical conduct of a pre
- rule study for which EPA and the HSRB have not reviewed the protocol 5 16 8 29 2,194 Store, file, and maintain records 4 8 6 18 1,388 Total per response 86 405 107 598 45,927 Annual Burden: 598 hours per protocol or completed study * 34 protocols or completed studies per ye ar = 20,332 hours Annual Costs: $45,927 per study * 34 protocols or completed studies per year = $1,561,518

8 C omme nts from the AHETF, AEATF, and ICR, Inc., indicated an average of 2 hours for management, 2 hours for technical, and 2 hours for clerical for the activity “Rule Familiarization and Training.” The Agency considers this burden to be representative of the time expenditure by experienced submitters. But EPA recognizes that there may be new inexperienced entities that may need to spend more time on “Rule Familiarization and Training.” In order to capture the total burden and cost across all submitters, both experienced and inexperienced, OPP assumed that, in addition to the experienced submitters, there would be one new

submitter per year, and that a new submitter would spend 4 management hours, 16 technical hours, and 2 clerical hours on “Rule Familiarization and Training.” The weighted average, covering both experienced and inexperienced submitte rs, is 2 management hours, 4 technical hours, and 2 clerical hours.**For ICR Table 2**

**Table 2. Respondent Burden and Cost Estimates** 

**– All Other Submitted Research**  **with Human Subjects Activities**  **Average Burden Hours Per Response**  **Total Per Response**  **Management $138**  **Technical**

**$73 Clerical** 

**$42 Hours**  **Cost**

**($)** Rule familiarization and training 1 1 0 2 211 Prepare and Submit Ethics In formation of Completed Human Studies to EPA 0 8 1 9 626 Store, file, and maintain records 0 0 1 1 42 Total per response 1 9 2 12 879 Annual Burden: 12 hours per study * 20 studies submitted per year = 240 hours Annual Costs: $879 per study * 20 studies submitted per year = $17,580**Agency Burden Hour Estimates: Technical Staff 9**  **Table E. Protocol Review** 

**Study Type Average Annual**  **Number of Protocols**  **Average Number**

**of Hours Per Protocol Review**  **Total Number**

**of Hours** AHETF 4 160 640 AEATF 5 120 600 Repellant Efficacy 6 80 480 Other T ypes of Post
- Rule Intentional Exposure Studies 1 80 80

Weighted Average Number of Hours per Protocol Review **113 hours per protocol**  Estimated Annual Number of Protocol Reviews **16 Table F.**  **Review of Completed Studies**

**Study Type Average Annual**  **Number of Completed Study**  **Reviews Average Number** 

**of Hours Per Completed Study**  **Review Total Number** 

**of Hours** AHETF 4 80 320 AEATF 5 60 300 Repellant Efficacy 6 40 240 Other T ypes of Post
- Rule Intentional Exposure Studies 1 40 40 Pre
- Rule Completed Intentional Exposure Studies that Measure or Id entify a Toxic Effect 2 60 120

Weighted Average Number of Hours per Protocol Review **57 hours per completed**  **study** Estimated Annual Number of Completed Study Reviews **18 Table G.**  **Ethics Reviews for Pre -**  **Rule Completed Studies Not Requiring HSRB Review**  **Study Type Average Annual**  **Number of Reviews**  **Avg. Number of**

**Hours Per Review Annual** 

**Burden Hour Estimate**  Pre
- Rule completed studies that do NOT measure or identify a toxic effect **20 4**  **80 hours**

9 Ag handler study e stimates based on information from J. Evans, M. Crowley and J. Carley (EPA/OPP). Antimicrobial exposure study estimates based on information from T. Leighton, C. Walls, and J. Carley (EPA/OPP). Insect repellant study estimates based on information from C. Fuentes, K. Sweeney, and J. Carley (EPA/OPP). Other study type estimates based on information from J. Carley, B. Jordan, and K. Sherman.**Burden Hour Estimates: Management and Clerical**

**Management:**  Assume 2 hours for Protocol Reviews and Completed Study Reviews  Assume zero hours for Ethics Reviews for studies not requiring HSRB Review **Clerical**  Assume 2 hours for Protocol Reviews and Completed Study Reviews  Assume 1 hour for Ethics Reviews for studies not requiring HSRB Review
**For ICR**  **Table 3 Table 3.**  **Weighted Average Burden and Cost Estimates for Agency**

**– Research**  **Involving Intentio nal Exposure** 

**Activities Average Burden Hours Per**  **Response Total Per**  **Response Management**  **$103 Technical** 

**$71 Clerical** 

**$41 Hours**  **Cost**

**($)** Rule familiarization and training 2 2 0 4 348 Primary Review of Scientific and Ethical Aspects of a Protocol 1 113 0 114 8,126 Primary Review of Ethical Aspects of a Completed Study Report 1 57 0 58 4,150 Secondary

Review of Scientific and Ethical Aspects of a Protocol or Review of Ethical Aspects of a Completed Study 4,144* Store, file, and maintain records 0 0 2 2 82 Total per protocol or completed study 4 172 2 178 16,850 ***** Cost of HSRB members working on the HSRB report (collectively spending 240 hours per HSRB report in FY 2008, compensated at the rate of $53/hour), plus the cost of EPA Office of the Science Advisor technical staff working on the HSRB report (171 hours per report, at the technical staff rate of $71/hour). Each HSRB report covers an average of 6 protocols and/or completed studies per report. Annual Burden: 178 hours per study or protocol * 34 protocols or completed

studies = 6,052 hours Annual Costs: 16,8 50 * 34 protocols or completed studies = $572, 900**Number of Transactions: February 2009 -**  **January 2012**

**1. AHETF Monitoring Program**   The AHETF monitoring program defines 33 scenarios, each of which will ty picall y involve 5 field studies. About 80 field studies will be needed to complete the program.  The AHETF plans to complete the program within 5 years.  ~30 scenarios in 5 years = ~ 6 scenarios & 6 protocols per year.  For each protocol, there will be a completed study report approximately

1 ye ar later = ~ 6 completed reports per year.  Note that approximately 50% of the time, protocols will need to go to the HSRB twice, either becaus e the AHETF chooses to present field studies associated with one scenario at two different HSRB meetings, or because the protocol is not reviewed favorabl y during the first visit to the HSRB.  **Original EPA Estimate (prior to consultation): 6 scenario**  **- spe**  **cific protocols**  and **6 scenario -**  **specific study reports** per year  **AHETF Estimate (from consultation): 4 protocols and 4 study**  **reports per year**  **Figures used in ICR: 4 protocols and 4 study reports per year, based**  **on AHETF’s consultation response 2.**  **AEATF Monit oring Program**   The AEATF monitoring program defines 17 scenarios, each of which will ty picall y involve a single field study. Some will likely be observational and thus will not need to undergo HSRB review

– according to Tim L.  The AEATF plans to complete the program within 5 years  ~15 scenarios / 5 years = ~ 3 protocols per ye ar.  For each protocol, there will be a completed study report, approximately

1 ye ar later = ~ 3 completed reports per year.  **Original EPA Estimate (prior to consultation): 3 scenario**  **- specific**  **protocols** and **3 scenario -**  **specific study reports** per year  **AEATF Estimate (from consultation): 5 protocols and 5 study reports**  **per year**  **Figures used in ICR: 5 protocols and 5 study reports per year, based**  **on AEATF’s consultation response 3.**  **Insect Repellent Efficacy Testing**   For the past two years we have averaged about 3 protocols or completed studies at each HSRB meeting.  This is about half the steady

- state demand under current requirements.  Therefore, ~ 3 protocols per year.  For each protocol, there will be a completed study report, approximately

1 ye ar later = ~ 3 completed reports per year.  **Original EPA Estimate**  **(prior to consultation) :**  **6 protocols** and **6 completed**  **studies** per year **Carroll -**  **Loye Estimate: an average of 4 protocols and 4 study**  **reports per year**   **ICR, Inc. Estimate :**  **an average of 2 protocols and 2 study reports per year**   **Figures used in ICR : 6 protocols and 6 study reports per year, adding**  **together the Carroll -**  **Loye and ICR, Inc. estimates 4.**  **Other Post -**  **Rule Studies**  These could include exposure studies from sources other than the task forces, ADME studies, skin patch tests of irritation or sensitization, sy stemic toxicity

tests, or others.  All would require submission of a protocol before execution and of a completed report after ex ecution; both the protocol and the report would require both EPA and HSRB review.  **Estimate: 1 protocol and 1 completed study per year.**  (This is likely an over- estimate) **5. Pre**  **- Rule Completed Studies which measure or identify a toxic effect**   2 categories:

 New submissions requiring submission of §26.1303 information
 Studies retrieved from the literature or from other sources, not subject to §26.1303.  There is likel y to be a steady trickle of these studies

– approximately 1 case every- other meeting  One case may include multiple individual studies with the same chemical  **Estimate** : **2 cases per year** (requiring study review, but not protocol review) **6. Pre**  **- Rule Completed Studies which do not measure or identify a toxic effect**   These studies do not go to the HSRB, but they do require an EPA ethics review.  Historical level: 20 reviews per ye ar  Assume workload to remain constant over the time period of the IC R  **Estimate : 20 per year**  (requiring EPA ethics review only

– not HSRB review)
**TOTAL TRANSACTIONS PER YEAR :**   **16 prot**  **ocols** per ye ar requiring EPA & HSRB review

o AHETF, AEATF, Insect Repellant, and one additional ty pe of post
- rule intentional exposure study  **18 completed study reports**  per ye ar requiring EPA & HSRB review

o 16 completed study

reports for which there was previ ous protocol review o 2 pre
- rule studies that measure or identify a toxic effect  **20 studies/year** requiring EPA ethics review, but not HSRB review (pre

- rule studies that do not measure or identify a toxic effect)