The Cancer Prevention and Research Institute of Texas (Institute) adopts the amendments to §§703.1 - 703.20, and new §703.21, concerning Grants for Cancer Research and Prevention. The amendments to §§703.3, 703.11, and 703.13 are adopted with changes to the proposed text as published in the November 15, 2013, issue of the Texas Register (38 TexReg 8074). The amendments to §§703.1, 703.2, 703.4 - 703.10, 703.12, 703.14 - 703.20 and new §720.21 are adopted without changes to the proposed text as published.

Reasoned Justification

The amendments and new section are adopted to clarify several existing rules, to reflect changes to the statute as amended by the passage of Senate Bill (SB) 149 (83rd Regular Session), for consistency with other chapters, and to provide additional guidance regarding the grant application review and award process and procedures, including the monitoring of grant award contracts. In addition, these amendments and new section are adopted pursuant to and in satisfaction of the provisions Texas Health and Safety Code, Chapter 102, and other relevant statutes.

Summary of Public Comments and Staff Recommendations

The Institute accepted public comments in writing and by fax through December 16, 2013. No comments were received regarding the amendments to the following rules: §§703.1, 703.2, 703.4, 703.7 - 703.9, 703.12, and 703.15 - 703.20. Comments were received from the University of Houston System ("UH"), the Texas Tech University System ("TTUS"), and the Crosetto Foundation to End Premature Cancer Deaths (Crosetto Foundation) regarding the proposal. The observations and suggested changes are provided in the following section-by-section summary of the comments received and the Institute's response. Changes were made to three sections, §§703.3(h), 703.11(b), and 703.13(a), based on the comments submitted and to correct a typographical error.

§703.3. Grant Applications.

UH and TTUS commented with regard to the proposed change to §703.3(h)(3) and suggest revisions. Generally, §703.3(h) refers to the required certification by the grant applicant that the applicant organization has not made and will not make a donation to the Institute or a supporting foundation. For purposes of the applicant's certification, subsection (h)(2) expressly includes the principal investigator, program director, or company representative, as well as the grant applicant's officers, directors, and senior members or key personnel listed on the application. In addition to those individuals, subsection (h)(3) requires the grant applicant's certification to account for any employee of the applicant organization, or a relative of the employee within the second degree of consanguinity or affinity, that makes a donation exceeding $500 to the Institute or a supporting foundation. UH and TTUS comments are limited to the inclusion of employees' relatives in the mandatory certification. UH points out that a principal investigator or project director may not have knowledge of donations that are made by relatives, particularly those that are related by a second degree connection. UH suggests restricting the certification to the primary investigator, project directors, and their immediate family members. TTUS comments that as a public institution of higher education, disclosing the identities of an employee's relatives is not required, nor is the information maintained as a condition of employment. Therefore, TTUS asserts that it is not feasible to require that an applicant certify at this level for purposes of §703.3(h)(3).

Response: The Institute agrees in part with the submitted comments and modifies §703.3(h)(3) retaining the majority of the proposed new language but changing the paragraph to exclude "a Relative of an employee" from the application of the rule. The Institute notes that although both UH and TTUS purport to address subsection (h)(3) specifically, their comments also encompass subsection (h)(2). The Institute amends subsection (h)(2) to delete the reference to "Relative of the following individuals" and replace it with "spouse or dependent child(ren) of the following individuals." The paragraph as amended appropriately balances the Institute's interest in ensuring that grants are not awarded to grant applicants that contribute to the Institute or a supporting foundation while recognizing the limits of the applicant organization's information with regard to the identity and charitable donations made by extended relatives of its employees.

Although TTUS does not recommend a specific rule change, it points out that requiring the grant applicant certification to be made at the time that the application is submitted may be problematic if donations are continuously accepted by the Institute. TTUS contends that the only time that an institution can make this certification is immediately following review of the list of donors provided by the Institute or any supporting foundation.

Response: The Institute's Chief Compliance Officer is statutorily charged with ensuring observance with the prohibition against donations. The Chief Compliance Officer is required to compare each grant application to a list of donors to the Institute or a supporting foundation before the application undergoes peer review and again before any grant is awarded to the applicant. The certification mandated by §703.3(h) assists the Institute in fulfilling the statutory directive. The Institute will facilitate the certification process by making a list of donors to the Institute or any supporting foundation publicly available. An amendment adopted for §702.7, Acceptance of Gifts and Donations by the Institute, requires that the Institute report information pertaining to gifts, grants, or other consideration provided to the Institute, an Institute employee, or an Institute committee member by posting the information on the Institute's website, including the donor's name, the date of the donation, and the amount of the donation.

In its comments regarding §703.3(b) and (e) in this rule, the Crosetto Foundation proposes that the Institute adopt standard evaluation criteria for all applications. The standard evaluation criteria require the applicant to demonstrate the objective capability to reduce cancer deaths and quantify the cost per each life saved compared to current costs. The Crosetto Foundation further suggests that applicants be required to quantify the expected percentage of cancer deaths and cost savings when the proposed project is tested on a sample population.

Response: The Institute declines to make the changes proposed by the Crosetto Foundation because the changes are too specific to provide general guidance. The Institute was established to create and expedite innovation in the area of cancer research leading to the medical or scientific breakthroughs in the prevention of cancer and cures for cancer; to attract, create, and expand research capabilities in the state to promote a substantial increase in cancer research and high quality jobs; and to develop and implement the Texas Cancer Plan. The potential areas for research and prevention projects included in the rule are broad in scope and may encompass areas addressed by Crosetto Foundation without the requested change to the rule. However, including the Crosetto Foundation's proposed changes may serve to unduly restrict the types of projects eligible for funding. It may be impossible to calculate with precision the Crosetto Foundation's criterion related to the expected reduction of cancer deaths for most, if not all, cancer research projects at the time applications are submitted. The Institute notes that the Crosetto Foundation's proposed requirement that applicants specifically quantify the reduction of cancer deaths and cost savings on a sample population appears to suggest that only those projects that are currently in clinical trials be eligible for funding. One of the Institute's statutory powers and objectives is to support research "in all stages in the process of finding the causes of all types of cancer in humans and developing cures, from laboratory research to clinical trials and including programs to address the problem of access to advanced cancer treatment." It is within the Institute's discretion to design grant programs to achieve these statutory objectives; the statute does not compel the Institute to restrict funding to a particular stage of research. The potential for scientific discoveries that will make a meaningful difference to cancer patients may occur at any stage in the research process. If the Institute limits funding at the outset to only those proposals that claim to demonstrate an immediate reduction in cancer deaths, early stage and developing research would suffer and potential treatment-altering innovations may be missed. The Institute notes that the rule as proposed does not prohibit the Institute from seeking the information suggested by the Crosetto Foundation or using the information as a specific criterion to evaluate the merit of the Grant Application.

§703.5. Scientific Research and Prevention Program Committees.

The Crosetto Foundation proposes two changes to subsection (c). The first change is to require each reviewer to provide scientific arguments and and/or references, calculations, demonstrations supporting his rejection of an applicant's project claim and/or the superiority in efficiency and potential of another project that the reviewer recommends for funding.

Response: The Institute declines to make this change because it describes a process that is inconsistent with the peer review process set forth in Chapter 703, particularly with regard to the Crosetto Foundation's recommended standard evaluation criteria. (See the Institute's response to the Crosetto Foundation's proposed standard evaluation criteria and other suggested revisions for §703.3.) The decision to recommend funding for an application is the purview of the scientific research and prevention program committee and is based on the sufficiency, scientific merit and, if applicable, the commercial prospects of the application. Requiring the reviewer to provide specific scientific counter-arguments for those projects not recommended for funding and comparisons to projects recommended for funding will significantly increase the time, expense, and resources necessary for the evaluation of grant applications.

The second change to subsection (c) suggested by the Crosetto Foundation is to include language that "Reviewers who had the vision of the benefit to the public from an innovation that proved reduction of cancer deaths and cost will be included in a list of expert reviewers in the field. Those who rejected funding for a project that later had success for the above goal (with CPRIT funding or funding from a different source) will be placed in a lower priority in the list of experts in the field." The Crosetto Foundation does not provide an explanation supporting this recommendation.

Response: The Institute declines to make this change. The Institute interprets the Crosetto Foundation's suggested revision to propose an eligibility criterion for Scientific Research and Prevention Program committee members that gives priority to a reviewer that previously approved grant funding for a project that proved to reduce cancer deaths and costs, while giving lesser priority to a potential reviewer that did not approve funding for a project that later was proven to reduce cancer deaths and costs. The change will not be made because the criterion creates an unreasonable burden on the agency and is too difficult to implement. It may be impossible for the Institute or a reviewer to determine whether a potential reviewer had the "vision of the benefit to the public" or the "proved reduction of cancer deaths and cost" for one or more previous grant or grants. Moreover, there may be reasons that are unrelated to a particular reviewer's evaluation of an application that the project was not funded by CPRIT or another grant-making entity, even if that project later proved to successfully achieve its aims.

The Crosetto Foundation suggests striking the phrase, "exceeding $5,000" from subsection (g). He does not provide an explanation for this recommendation.

Response: The Institute declines to make the suggested change. The $5,000 limit for compensation for professional services rendered to a grant recipient within one year of the grant award is de minimis and balances the Institute's interest in ensuring the integrity of its grant review process while not unreasonably restricting the reviewer's employment opportunities.

§703.6. Grants Review Process.

UH comments that in order to avoid a conflict of interest, "all applicants should disclose their collaborators, mentors, and postdoctoral fellows so that an unbiased scientific merit of the proposal can be obtained."

Response: The Institute declines to make this change because the issue is addressed by another rule, §702.11(d), which defines professional conflicts of interest requiring recusal from the grant review, discussion, and deliberation. Specifically, §702.11(d)(5) states that a professional conflict of interest exists if the individual subject to this rule is "a colleague, scientific mentor, or student of a senior member or key personnel of the research or prevention program team listed on the grant application, or is conducting or has conducted research or other significant professional activities with a senior member or key personnel of the research or prevention program team listed on the grant application within three years of the date of the review."

TTUS comments that the review of grant applications should take into account geographic considerations. TTUS acknowledges that the review of applications for prevention grants does incorporate geographic considerations, but contends that accounting for the "well documented geographic disparity in cancer research, care and prevention" would benefit West Texas "if reviewers were tasked with also looking at the geographic aspects of the grant." TTUS does not provide specific changes to the proposed rule text.

Response: The Institute declines to make a change to §703.6 because the suggested changes are already addressed in §703.7, Program Integration Committee Funding Recommendation. Section 703.7 reflects the statutory requirement that the Program Integration Committee give priority to proposals that, among other considerations, enhance research superiority at institutions of higher education in this state by creating new research superiority or attracting existing research superiority from institutions not located in this state. Another priority consideration the Program Integration Committee may consider in making its award recommendations is the ability of the grant project to fulfill the goals of the Texas Cancer Plan. TTUS acknowledges that the Texas Cancer Plan calls for addressing the disparities in available cancer research and care that occur in rural areas of Texas.

The Crosetto Foundation provides two comments for subsection (a)(1). First, the Crosetto Foundation proposes all applicants "should estimate and then provide a plan to measure the results on a sample population." He contends "that a difference or no difference in the mortality rate will quantify the success or failure of a proposed solution." The Crosetto Foundation supports this change by referring to a mandate "for a significant reduction in cancer deaths and cost per life saved compared to current cost." The Crosetto Foundation's second suggested change is to add "with the highest potential to reduce cancer deaths and cost per each life saved compared to the current cost" following the words "Cancer Prevention and Control projects."

Response: The Institute declines to make these changes because the changes describe a process that is inconsistent with the peer review process set forth in Chapter 703, particularly with regard to the Crosetto Foundation's recommended standard evaluation criteria. (See the Institute's response to the Crosetto Foundation's proposed standard evaluation criteria and suggested revisions for §703.3.) The proposed change limits the legislative purpose for the Institute and unduly restricts the types of projects eligible for funding by requiring a specific quantification of the reduction of cancer deaths. Pursuant to Health and Safety Code §102.002, the Institute was established to create and expedite innovation in the area of cancer research and to enhance the potential for a medical or scientific breakthrough in the prevention of cancer and cures for cancer; to attract, create or expand research capabilities of institutions of higher education and other public or private entities; and to develop and implement the Texas Cancer Plan. The potential for innovative scientific discoveries that will make a meaningful difference to cancer patients can occur at any stage in the research process. If the Institute limits funding at the outset to only those proposals that claim to demonstrate an immediate reduction in cancer death, early stage and developing research would suffer and potential treatment-altering innovations may be missed. Furthermore, it may be impossible to calculate this figure with precision for most, if not all, basic and translational cancer research projects at the time applications are submitted. The Institute notes that the rule as proposed does not prohibit the Institute from seeking the information suggested by the Crosetto Foundation or using the information as a specific criterion to evaluate the merit of the Grant Application.

The Crosetto Foundation proposes two changes to subsection (c)(3). The first change requires each reviewer to provide scientific arguments, calculations, reference data, and logical reasoning that comply with the Crosetto Foundation's proposed standard evaluation criteria for determining whether to approve or reject an application.

Response: The Institute declines to make this change because it describes a process that is inconsistent with the peer review process set forth in Chapter 703, particularly with regard to Crosetto Foundation's recommended standard evaluation criteria. (See the Institute's response to the proposed standard evaluation criteria and suggested revisions for §703.3.)

The Crosetto Foundation's second change to subsection (c)(4) proposes a post hoc evaluation of the reviewer. According the Crosetto Foundation's proposal, a reviewer will be judged as "an expert, knowledgeable person" based upon the successful experimental results on a sample population of a project approved by the reviewer and will be included on a list of "experts to reduce cancer deaths and cost." Conversely, the Crosetto Foundation recommends that "reviewers that could not recognize the scientific value and potential of a proposal that demonstrated benefits or who approved projects that demonstrated a failure will be removed from the list of experts in reducing cancer deaths and their arguments to reject or approve projects will be included in a list of pitfalls so that the same errors should not be repeated in the future of stopping or delaying the benefits from innovations."