Abstract

Clinical outcomes research is important to expand the body of evidence for safe and effective use of naturopathic modalities. This paper provides guidance for establishing a practice outcomes monitoring and evaluation system (POMES). General considerations are given for integrating specialized research ethics requirements into a naturopathic practice, and for creating a research plan for collecting data in the office setting. Practical issues such as data management and staffing are also discussed. The iterative process of designing a POMES for evaluating breast cancer outcomes in a naturo- pathic clinic is described. Outcomes monitoring in the naturo- pathic practice setting can lay the foundation for participation in collaborative studies to assess the efficacy of naturopathic medicine.

Introduction

In 1997, the Office of Alternative Medicine (OAM) and the National Cancer Institute (NCI) began promoting the concept of a practice outcomes monitoring and evaluation system (POMES), the purpose of which is to collect outcomes data on complementary and alternative medicine (CAM) treatments currently in use for cancer patients (1) . The Office of Cancer Complementary and Alternative Medicine of the National Cancer Institute has since adopted the promotion of this model (2) . The POMES can be utilized to improve the body of evidence for safe and efficacious use of CAM modalities that have not been evaluated by the standard pharmaceutical research model. Conventional medical treatments are assessed for toxicity levels, biologic activity, and adverse event occurrences before becoming available for commercial therapeutic use. In CAM, most therapies have been used in humans for some time, but most with only anecdotal evidence of their potential toxicities, actions, and clinical results.

As a means of reporting the results of treatment, outcomes research is a natural extension of the desire to follow the progress of one’s patients, and is important from scientific and professional standpoints to substantiate and disseminate best clinical practices. In the hierarchy of supporting evidence, expert opinion, case studies, single case-control studies, and systematic reviews of case-control studies provide weaker scientific evidence than do outcomes studies, cohort studies, and randomized controlled trials (3) . Most CAM therapeutics are taught and prescribed based on historical and expert opinions and case studies. Developing case-control studies and randomized controlled trials may provide practical and ethical challenges for the CAM provider, such as obtaining adequate funding, and patient/provider willingness to participate in a study with a non-CAM treatment or placebo arm.

Outcomes studies, on the other hand, can be integrated into the usual operation of the naturopathic medical clinic (4) . Many pieces needed for outcomes research are already collected as part of routine practice. Demographic data are often gathered from patients through an intake form mailed to the patient or given at the initial office visit. Diagnostic and prior treatment information is collected through the intake form, by physician interview with or without a standardized history form in chart notes, from previous medical records, and through laboratory reports. Follow-up information may be collected through survey mailings, phone interviews, or scheduled practitioner visits. Outcomes monitoring can be conducted on a number of common conditions or on treatment modalities.

The purpose of this paper is to provide general considerations in the development of a registry and practice outcomes monitoring evaluation system, and to provide an example of how this process was implemented in the development of a POMES research plan for breast cancer patients treated in a naturopathic medical clinic. Specific recommendations are made to facilitate the integration of outcomes research into naturopathic practice.

Process of Developing a Registry and POMES

The first step in creating a registry and POMES is defining a scientific question concerning the condition or treatment outcome to be studied. A registry is a collection of medical data on patients; in this case, those seen in a naturopathic medical clinic. This generally includes demographic, diagnostic, and treatment information. The registry can be used to characterize the patients who choose to visit ND practices, for what diagnoses, and which treatment modalities the ND provider selects for given conditions. Initiating a practice outcomes monitoring and evaluation system expands on the registry by documenting the clinical outcomes of these patients, such as survival or quality of life.

If the observational design of the POMES will yield an interpretable answer to the scientific question posed by the investigator and his/her team, then the next step is to create the research plan. The research plan will define eligibility criteria for the study, explicitly stating which patients in the practice will be approached to participate and how recruitment will take place. The plan also describes the method for collecting and managing the data consistently for each patient. It includes copies of all forms, interview scripts, and data tracking documents used in the study. It will also summarize measures taken for human subject protection, including procedures pertaining to any adverse events observed. Once drafted, the plan should be submitted to a source knowledgeable on research design and methodology, such as the scientific review committee at a naturopathic academic center, for feedback and recommendations to optimize the study’s ability to answer the scientific question.

To safeguard the rights of participants contributing data to the study, several protective procedures must be observed. The practitioner must acquire a project-specific formal agreement from each patient agreeing to participate in the registry and/or POMES, known as an informed consent. The consent required for medical research is different than that for medical treatments; participation and use of data for research purposes is a voluntary act separate from the decision to seek medical treatment. Sections that must be included in a research informed consent form are:

1. the purpose of the research and the patient’s role in the study,
2. benefits of participation, if any,
3. study procedures,
4. compensation, if any,
5. risks of participation,
6. confidentiality plan,
7. iteration of volunteerism and right to withdraw without effect on future care,
8. alternative treatments that are available,
9. where to direct questions concerning the study (5) .

Further requirements are also in place for vulnerable populations such as children, prisoners, pregnant women, and the mentally ill. The investigator explains the procedures, risks, and benefits of the study, and if the patient agrees to participate then he/she signs the consent form. Scientific journals may not publish findings from studies in which informed consent was not obtained (6) . For more information on the protection of human subjects requirements, see the Code of Federal Regulations at http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

The researcher must use additional language to address the privacy restrictions on personal health information use enacted by the Health Insurance Portability and Accountability Act (HIPAA). Any health information collected for research purposes is regulated by HIPAA; again, research require- ments are slightly different than those for medical service alone because of the added dimension of voluntary participation. HIPAA requirements can be addressed as part of the informed consent form or as a separate document. For more information, visit http://privacyruleandresearch.nih.gov/pr_02.asp.

Both the informed consent and the HIPAA documentation are reviewed by an Institutional Review Board (IRB; also known as a Human Subjects Committee or Board) for appropriate elements and design, and to ensure that patients are not inadvertently coerced into participation. Any academic research institution, including four of the naturopathic colleges, has an IRB(7) and many will review proposals from outside agents for a fee. Alternatively, independent Institutional Review Boards exist who will oversee and approve the human subjects requirements for investigators (see http://www.hhs.gov/ohrp/ for listings). Again, most journals require demonstration of IRB oversight, HIPAA compliance, and research protocol review before considering publication.

The Institutional Review Board may recommend that a Data and Safety Monitoring Board (DSMB) be created to independently monitor the study and ensure ongoing protection of participants. The DSMB consists of professionals in the field under study and experts in research methods, and may include a biostatistician or other data analysis specialist. The DSMB will periodically review the data collected by a study to assess whether any subject grouping experiences exceptional benefit or harm. The DSMB can make recommendations to alter the study protocol or to stop the study if subjects are found to be at risk, based on the data presented. For more information on the use of data and safety monitoring board, go to http://www.nihtraining.com/ohsrsite/irb/Attachments/51_DSMB.htm.

Consideration is warranted concerning the proper collection and use of data, including patient privacy assurance and the training of data entry assistants. It is important for a data specialist to monitor and “clean” the data of errors (examine data for mis-entry, missing information, etc.), and ultimately, to organize and analyze the data in a scientifically meaningful way. Ideally, the data specialist will be engaged from the planning stages of the study to assist in defining the experi- mental plan, the protocol, and safety monitoring to ensure that the data collected can be efficiently used to answer the scientific question.

Example of this Process for Breast Cancer Survival Outcomes Monitoring

Outcomes research is being pursued in the case of breast cancer, and recent published literature illustrates the importance of establishing outcomes monitoring in naturo- pathic care of breast cancer patients. A study examining the survival outcomes of breast cancer patients receiving treatment similar to those used by naturopathic physicians (8) reported no improvement in breast cancer specific survival or disease-free survival with mega-dose vitamins and minerals (9) . A study examining the use of alternative medicine in oncology patients found that users of alternative medicine had poorer survival outcomes during the 8-year follow-up, after adjustment for disease related negative prognostic factors (10) . What little data exist at this time suggests that the multi- modality style of treatment practiced by naturopathic physicians is ineffective or possibly detrimental in promoting longer survival in cancer patients. With at least some CAM therapies for breast cancer under question, the need for further research is clear.

Using the process described, a registry and POMES was designed to collect preliminary data on women treated naturo- pathically for breast cancer. A primary goal of this system is to characterize the women who seek naturopathic care for their breast cancer. A second goal is to acquire preliminary, descriptive data concerning their survival outcomes over five years. This study was designed for administration by a research staff in a private medical office, though it can be modified to be conducted by qualified and trained office staff. When a new patient calls to make an appointment, the scheduler will assess her chief complaint. Any woman reporting primary breast cancer as her chief complaint will be assessed for interest in participation in the registry and the practice outcomes monitoring and evaluation study. The informed consent and HIPAA forms will be sent along with the initial patient intake form prior to the first office visit. This will allow patients time to thoughtfully consider the study prior to their initial appointment. The practitioner will elicit and respond to any questions the patient may have concerning the study before requesting written consent.

Table 1: Data collection schema for Registry and POMES.

Study Milestone	Data Collected
At enrollment(Registry)	Demographic information
	Personal and emergency contact information
	Date of diagnosis
	Age at diagnosis
	Breast cancer type, location, tumor(s) size/grade/stage (at diagnosis and most recent)
	Estrogen receptor/progesterone receptor status
	Her-2/neu gene expression
	Regional/distant metastasis
	Name and contact information for treating oncologists