Challenges from the academic environment

Academic medicine is currently at a profoundly low ebb. Reduced reimbursement, increased workloads, decreased resident help, limited donations, and tight NIH budgets have resulted in a significant squeeze on financial and personnel support for academic medicine. Only those clinician scientists who have great passion and tenacity will survive in these trying times. Unless the NIH substantially increases its support for clinical scientists to conduct research and clinical trials, this negative...

Cancer Trials Support Unit Ctsu

In an attempt to improve the rate of accrual to phase 3 trials, and to leverage advances in technology and communications, NCI created the Cancer Trials Support Unit. Its primary goals are to centralize regulatory support for Cooperative Group trials, previously maintained separately by the eight adult Cooperative Groups, and to establish a national network of physicians who can participate in NCI sponsored phase 3 adult cancer treatment trials, without regard for their individual Group...

Introduction

The Cooperative Group Program of the National Cancer Institute (NCI) was founded in 1955 when several pioneering cancer researchers approached the United States Congress for increased financial support for the study of chemotherapy for cancer. In response to this request, 5 million was appropriated to the NCI to establish the Chemotherapy National Service Center.1 By the late 1950s, the program included seventeen NCI-funded groups that were engaged in the study of new agents from the NCI's drug...

Q How do I search for these alternatives

A Electronic database searches are often the first step. In the eyes of government regulators and many IACUCs, they are seen as crucial. The federal government's Animal Welfare Information Center maintain a staff and a website that are helpful in learning how to conduct literature searches targeted to finding information about animal alternatives. They also produce bibliographies on common topics. The search must be narrowed down, using keywords such as alternatives, in vitro, blood collection...

Financial Conflicts Of Interest

A professor learns of a novel prevention strategy for a lethal disease. He conducts a clinical trial that is 100 successful and now wants to charge a fee to use the information and prevent the disease's effects on the rest of his city's population. While this may sound like a dilemma causing angst between administration and faculty at a modern medical school, this actually took place in 1799 at Harvard when one of its three professors, Benjamin Waterhouse, became familiar with Jenner's strategy...

Oversee the conduct of audits

Additional responsibilities of the CTMB relate to overseeing the conduct of on-site audits and reviewing compliance with federal guidelines. Specific roles of the CTMB include 1. The CTMB staff reviews the scheduling of all audits. In order for CTMB to assess compliance with the required frequency of audits, all cooperative groups must maintain a comprehensive and updated tabulation of its member institutions. Such a roster must include the following details 1) dates on which the institution...

Identify local community norms

In communities with a significant 'special population' (African American, Hispanic, Native American), patient advocates can be particularly helpful in helping to identify community norms and function as an intermediary with the community. For instance, in many Native American traditions, important information is communicated not through a newspaper or other media, but through word of mouth and through story telling by a trusted community 'elder.' An important source for credible information in...

Legal Basis for IND Process

Clinical investigations are conducted under Investigational New Drug (IND) applications and are described at 21 CFR 312. The IND regulations provide a mechanism to support the safe use of unlicensed investigational products (drugs and biologicals) in human clinical investigations and provide a mechanism to allow interstate shipment of products not approved for marketing The authority citation for 21 CFR part 312 is cited in 312.1- Scope, which states that the authority is derived from the...

Q What principles guide Institutional Animal Care and Use Committee deliberations

IACUCs have responsibility for oversight of the use of animals in experiments, as well as for their procurement, housing, health and veterinary care. IACUCs focus on efforts to minimize any potential pain or distress that research projects might cause the animals. This includes assuring that animals used for research are healthy, that efforts are made to reduce their numbers to the minimum required for sound scientific data, that anesthetics and analgesics are used when appropriate and that...

Q What is your study design

A Portions of melanoma obtained either from biopsies or from operative specimens will be processed and prepared as single cells to be frozen in liquid nitrogen. Patients will be randomized to receive vaccine or a placebo. Patients will be followed for development of metastases. In addition, periodic blood samples will be taken to look for evidence of immunity. Genetic analysis of the tumors will be carried out to see if markers can identify patients who are likely to respond to the vaccination...

Cancer Treatment

In 2001, the Children's Oncology Group was formed by the merger of the four major pediatric clinical trials groups based in North America the Children's Cancer Group, the Pediatric Oncology Group, the National Wilms' Tumor Study Group, and the Intergroup Rhabdomysosarcoma Study Group. The collective achievements of these groups over the past four decades have lead to effective treatments for childhood cancers that have significantly improved the cure rates for childhood malignancies, including...

Q Must I consider alternatives How do I do that

A You must consider alternatives to procedures that may cause more than minor or momentary pain or distress to the animals. Start by considering which procedures those might be. In this project, for the initial polyclonal immunization, you will need to inject adjuvants, and they can cause painful inflammation. You will need to collect blood samples in the mice. You will need to euthanize them and collect their spleens. Later, once you've generated a hybridoma that produces the monoclonal...

Q How can animal distress be recognized and treated

Not all animal distress or illness involves pain nonetheless, it is still a serious animal welfare concern that must be addressed. Russell and Burch identified a typology of inhumanity (i.e., pain and distress) in the animal laboratory, noting that some distress is inherent to some experiments (direct inhumanity), and some is extrinsic (contingent inhumanity).3 As a general rule, any induction of disease should be considered a possible source of pain and or distress. In cancer studies, this...

Q What is your subject selection

A There are a number of important issues to be addressed with respect to subject selection. First, is the group of subjects selected to the research appropriate Is that population available to the investigators. Second, you must address how the number of patients was determined. It is very important to enlist the help of a statistician to do a careful and thoughtful power analysis. These analyses are always subject to some speculation. For example, it is often difficult to determine what the...

NBCCFs Clinical Trials Initiative

NBCCF's Clinical Trials Initiative incorporates the belief that advocate involvement is imperative to changing clinical trials. Therefore, the Initiative's strategies are based on the rich potential of connecting the power and perspective of trained advocacy with the expertise of science and health care. To put the Initiative into action, the Coalition developed programs to equip advocates with the information needed to participate fully in all aspects of the clinical trial process. Advocates...

Challenges

The major challenge facing the Cooperative Groups involves improving efficiency and productivity of the cancer clinical trials system - given limited resources - while preserving and enhancing its strengths and the quality of its work. There is an urgent need to enhance the timeliness of clinical trial accrual to accelerate drug and device development and expand access to new therapies. The existing regulatory structures for the oversight of clinical research are complex and often of uncertain...

Develop a patient to patient letter

This suggestion, similar to a flyer or brochure, is much more personal. First developed by breast cancer Patient Advocates at UCSF as a general information piece about clinical trials, this deceptively simple mechanism of sharing information has proved extremely successful. Such a document is available through the ACOSOG Education Committee. It capitalizes on the high level of trust that patients have of information endorsed by other patients (demonstrated by the Harris Interactive Survey). The...

Medical and community outreach

A Patient Advocate might be willing to attend local medical meetings (e.g., nurses, oncologists, surgeons) to 'exhibit' or make available information to health professionals about particular clinical trials. A patient advocate can make sure that information about the study is available in cancer patient education resource rooms or areas. A Patient Advocate might speak to 'target' community groups about clinical trials in general, e.g., retirement communities, or other groups with a heavy...

Institutional challenges

The current healthcare environment is such that reimbursement for a medical service is at its lowest in the last ten years. Therefore, it is incumbent upon hospital administrators to make sure they are in the black with respect to the operation of the medical center. For academic institutions with medical schools, the operations of the medical school and medical practices must be in the black as well. Over the past 10-15 years, medical practice has evolved significantly from relatively simple...

Symptom Control Quality of Life Survivorship

Cooperative group trials have also addressed complex questions regarding symptom control and quality of life in patients receiving therapy or palliative care. Quality of life scores have been used to determine if control of symptoms - pain, fatigue, nausea, anorexia and cachexia, chemotherapy-related anemia, depression, hot flashes - translates to an improvement in quality of life. For example, contrary to anecdotal reports and some small studies, results of a North Central Cancer Treatment...

Q What other animaluse regulations does the FDA impose

The FDA's oversight of animal use focuses on assuring the quality of the data generated in animal studies. FDA regulations include standards for animal identification, for avoiding accidental exposure to test substances, and assurance that food, water, bedding and pest control materials do not compromise the study in any way. Animals should be free of health problems that could complicate a study, and potentially infected animals must be isolated, if necessary, to control contagion. Data...

C Legal issues

In the practice of medicine, any deviation from established standards of care or negligence may be brought up by patients in the form of litigation. Such cases will be processed through the legal malpractice system. Medical malpractice law is a specialty within the legal system. Therefore, when a patient decides to sue, he or she will be represented by a plaintiff malpractice lawyer and the notification to the physician will be made. Upon receipt of such notification, a defense malpractice...

Function Sophisticated

The scope of advocate involvement beyond disease and administrative committees depends on the cooperative group. In some groups, patient advocates participate in scientific direction committees and data safety monitoring committees in addition to disease committees. In others, the patient advocate committee chair is a member of the Executive Committee and participates in prioritization of protocols and group policy decisions. In CALGB and ECOG, groups with a longer advocate history, advocates...

Cancer Clinical Trials Proactive Strategies

CANCER CLINICAL TRIALS PROACTIVE STRATEGIES Steven T. Rosen, M.D., Series Editor Sugarbaker, P. (ed) Peritoneal Carcinomatosis Principles of Management. 1995. ISBN 0-7923-3727-1. Dickson, R.B., Lippman, M.E. (eds) Mammary Tumor Cell Cycle, Differentiation and Metastasis. 1995. ISBN 0-7923-3905-3. Freireich, E.J, Kantarjian, H. (eds) Molecular Genetics and Therapy of Leukemia. 1995. ISBN 0-7923-3912-6. Cabanillas, F., Rodriguez, M.A. (eds) Advances in Lymphoma Research. 1996. ISBN 0-7923-3929-0....

Identify barriers to accrual in community

Sometimes when clinical trials are activated and opened with little input from Patient Advocates during their development, barriers become apparent after the fact. For instance at a (non-ACOSOG) trial in Chicago, one of the criteria was that future care be transferred to the trial site which was located in the midst of a heavily trafficked, congested area of the city. Patient Advocates could have anticipated the reticence of suburbanites to visit this area on a regular basis and could have...

Public Policy

Another way in which advocates influence clinical trials is by impacting legislation that plays a role in breast cancer research. In order to conduct these lobbying efforts, NBCCF - which is classified as a 501(c)(3) educational non-profit - relies on its sister organization, the National Breast Cancer Coalition (NBCC) - which is classified as a 501(c)(4) - its lobbying arm. The work of advocates under the umbrella of NBCC focuses on legislative priorities that will increase funding for breast...

Description Of The

The Food and Drug Administration (FDA) is a Federal agency in the Department of Health and Human Services with scientific, regulatory and public health responsibilities. The FDA mission statement notes that the FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, the nation's food supply, cosmetics, and products that emit radiation The FDA is also responsible for advancing the...

Preface

According to the American Cancer Society, about 1 million persons in the United States will be diagnosed with solid cancer every year. About 50 of them will be potentially cured by surgery. The other half of the population may develop metastatic cancer. To date, there is no systemic treatment available to cure metastatic cancer. Therefore, cancer clinical trials are critical to evaluate reliable treatment modalities against metastatic cancer. Likewise, adjuvant trials are needed to prevent high...

The Cocs Role As A Facilitator Of Quality Improvement Activities

Critical to the BA functions provided by the College to CoC-approved cancer programs is the ability to receive a limited data set that defines cancer care practices at each local facility. Analysis of these data sets becomes the basis for the feedback the College provides the programs about quality cancer care practices and how each facility compares to similar facilities at the aggregate level. The August 2002 final regulations permitted use of a limited data set for research, public health,...

Supplemental Marketing Claims

The guidance on new cancer treatment uses for marketed products builds on the principles of the clinical evidence of effectiveness guidance, and describes several scenarios of the type and quantity of the clinical evidence that may be adequate to support approval for additional use claims. All are based on the determination that the product is safe and effective in at least one cancer indication. A single adequate and well controlled multicenter study with appropriate endpoints demonstrating...

Q What special welfare concerns does production of genetically modified rodents entail

The creation of new strains of transgenic rodents raises concern for the manipulations of the animals (including surgery of both the males and females), the need to monitor new phenotypes for adverse outcomes, animal identification methods, and biosafety issues. Rodent surgery requires that the PI address the same issues raised by frog surgery, including aseptic technique, safe and effective anesthesia, and effective post-operative care, including use of post-operative analgesics. Laparotomy...

References

Uneasy Alliance Clinical Investigators and the Pharmaceutical Industry. N. Eng. J. Med., 2000 342 1539-1544. Available online at 2. Campbell, E., Koski, G., Zinner, D., and Blumenthal, D. Managing the Triple Helix in the Life Sciences. Issues in Science and Technology, Winter, 2005 1 32-39. National Academies Press, Washington, DC. Available online at http www. issues, org 21.2 campbell .html. 3. Christian, M., Goldberg, J., Killen, J., Abrams, J., McCabe, M., Mauer, J., and...

The Impact Of Quality Assurance Audit Programs On Site Conduct Of Clinical Trials

The educational benefits of an audit program are multifold. The audit experience emphasizes to the investigators the need for meticulous trial conduct and record-keeping. Through audits, the investigators become familiar with the standards of documentation as well as with the regulatory requirements of human subject research. Additionally, most cooperative groups allow investigators to participate as audit team members and actually conduct on-site audits. This peer-review process gives...

Accelerated Approval

The accelerated approval program was initiated in the 1990s as a mechanism to allow promising products intended to treat serious or life threatening diseases that provide meaningful therapeutic benefit to patients over existing treatments (21CFR 601.40) . Meaningful therapeutic benefit means treating patients whose disease has not responded to available therapy or patients who do not tolerate or the response is an improvement over available therapy. The phrase available therapy should be...

Field Of Dreams

No one would be surprised that a sweeping proposal for a national research system engenders great skepticism. Many will likely argue that such a system would be too expensive, that it would be too complicated, that it would be insensitive to local considerations important to the ethical review and conduct of the research, among a host of other objections. However, it is generally easier to give into skepticism that to venture forth into new territory-real progress is unlikely to occur until...

Individual challenges

The major motivating force for the PI to conduct clinical trials is twofold. First, he or she may be morally compelled to develop a better treatment to alleviate the suffering patient. Second, he or she may be motivated to be the first to find a solution for a difficult clinical problem or a cure for an incurable disease, such as cancer. Although the second motivation is important, the overriding reason for designing and conducting a trial should be to alleviate human suffering. In clinical...

Informed Consent

Another logical role for advocates is to make sure informed consent explanations are at an appropriate literacy level, reflect cultural sensitivities and are written in 'plain language' as much as possible. Advocates also review the protocol to ensure that the template consent form cooperative groups use includes all aspects of the protocol, with special note of issues important to patients. These may include what costs the patient will be responsible for, how many visits will be necessary,...

Communication of audit assessments

The initial communication of audit assessments takes place during the exit interview at the conclusion of the on-site audit. This is typically conducted by the audit team with enrolling investigators, research staff, and possibly the research regulatory personnel from the institution. As preliminary findings are discussed, the exit interview serves as a forum for face-to-face discussion, information exchange and education. A preliminary report of audit findings must be completed by the...

General Ethical And Legal Principles

The physician investigator conducting cancer clinical trials must be cognizant of the ethical and legal principles that form the basis for the regulatory environment described above. The general ethical principles applied in research involving human participants identified in The Belmont Report13 are summarized by Dr. Robert J. Levine in his important work entitled Ethics and Regulation of Clinical Research.14 These ethical principles include respect for persons, beneficence and justice. The...

Independent Projects

Advocate initiated, patient focused research projects have become part of the cooperative group picture as patient advocates have become more integrated. Among these are a pilot project in CALGB sending recently enrolled participants a letter thanking them for enrolling in a clinical trial, ECOG advocates' development of early trial closure notification guide lines (adopted by the Coalition which recommends these to its Cooperative Group membership), a pilot project on patient notification of...

Charging for Investigational Products

The IND regulations, in 21 CFR 312.7, address the issue of charging for investigational products. Although commercialization and marketing are prohibited, a sponsor may charge for an investigational product, with the charges limited to cost recovery for manufacture, research, development and handling of the product. Charging for ancillary services and the cost of care routinely provided for treatment of the underlying disease or condition are not regulated by the FDA. Two cases for charging are...

What Impact Will Hipaa Have On The Cocs Role

HIPAA standards apply only to health care providers who transmit any health information electronically, health plans, and health care clearing houses, i.e., 'covered entities' (HHA OCR, Feb. Mar. 2003). Hospitals, i.e., 'covered entities' could maintain their relationship with the CoC as long as a Business Associate agreement that met federally mandated requisites existed between the covered entity and the business associate (45 CFR Section 160.103). By definition a Business Associate (BA) is...

Q How can animal pain be recognized

The United States government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training state that unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain and distress in other animals.4 This is often the starting point in deciding whether animals are likely to be in pain related to an experimental protocol or not. Beyond this critical anthropomorphism, diagnosing...

Obligations For The Pi

In general, clinicians are well trained to practice their medical specialties. When they join the staff of an accredited hospital, they are given the bylaws of the hospital so that they understand what is expected of them. However, when a clinician steps into the world of clinical research as the PI of a research study, he or she assumes responsibilities that are new and at times foreign. The first and foremost step that a PI must take is to observe an urgent clinical problem and develop a...

History

Grace Monaco was the first patient advocate to work with a pediatric cancer group in 80s. Martha Romans was the first GOG advocate in the early 90s, followed by Mary Lou Smith and Mike Katz with ECOG, and Deborah Collyar with CALGB in the mid 90s. Pat Halpin-Murphy began working with NSABP and Wayland Eppard with NCCTG in the late 90s. ACOSOG (Barbara Parker) and ACRIN (Barbara LeStage) are the most recent cooperative groups to create patient advocate committees. Currently eight of the nine*...

Special Protocol Assessments

A program based in the 1997 FDA Modernization Act (Public Law 105-115 Section 119) established a mechanism for reaching agreement between the FDA and a sponsor on the design of a protocol intended to support marketing approval. Three classes of protocols have been designated as qualifying for special protocol assessment Clinical protocols intended to form the primary basis of an efficacy claim The outcome of a Special Protocol Assessment is a binding agreement between the FDA and the sponsor...

Selection of the onsite audit team

The audit team should be composed of staff who are familiar with the federal requirements of the audit process, the conduct and regulations of clinical trials, and the protocols being audited. The CTMB guidelines specify that at least one member of the audit team should have sufficient medical background as to verify patient eligibility, assess protocol compliance and review medical interventions. It is also important to recall that members of the CTMB or any other federal agency may choose to...

The Audit Process And How To Ensure A Successful Audit

Nancy You, MD M Lisa Jacobs, MD 2A Elizabeth Martinez, LPN, BS 4 David M. Ota, MD 3 4 ' Department of Surgery, Mayo Clinic, Rochester, MN 2 Deparment of Surgery, John Hopkins University, Baltimore, MD 3Department of Surgery, Duke University Medical Center, Durham, NC 4 American College of Surgeons Oncology Group, Durham, NC, USA Supported by the Ruth L. Kirschstein National Research Service Awards Training Grant T32CA101695 and the American College of Surgeons Oncology Group Grant...

Towards The Future

CTEP's commitment to the development of new drugs and better multi-modality treatments is evidenced by a solid track record of past accomplishments (Figure 14) and by novel approaches that address new challenges. The ability to combine multiple targeted agents early in their development, the inclusion of correlative science endpoints in the majority of phase 2 and 3 trials, and the integration of functional imaging approaches in early trials exemplify some of these innovations. In the phase 3...

Q Must I consider alternatives

You must explain to your IACUC why you require surgical collection of early-stage oocytes rather than harvesting later-stage oocytes that the female has passed (possibly in response to hormone injections). You must justify the numbers of frogs you will use. Because the frogs themselves are not units of statistical comparison in this project, numbers are justified based on the need for oocyte membranes, how many you can get from a single surgery, and how many surgeries you will...

Q How do you compare your protocol to standard treatment

A Most studies are designed to compare a new treatment to what is considered to be standard treatment. Often this an elusive term. Is a relatively ineffective treatment that is commonly used the proper comparison group to a novel treatment or is the proper comparator no treatment This is more relevant question when an effective regimen is accepted by the medical community. In this section of the application, the IRB will be expecting you to explain why it is acceptable to allow subjects to...

Why Clinical Trials

The grassroots advocates who make up NBCCF recognize that clinical trials provide the most effective venue to determine how to prevent, treat, and cure breast cancer. We often hear the statistic that less than three percent of adult cancer patients in the United States currently participate in clinical trials. Many trials either take too long, or are not long enough. Some never accrue a sufficient number of patients to adequately inform - or even begin - the trial. NBCCF asked the question What...

High Standards for Clinical Trials

When NBCCF chooses to participate in a clinical trial, they bring the power and the trust of a nationwide grassroots advocacy network. Therefore, before engaging in a collaboration, NBCCF evaluates every clinical trial according to rigorous principles. To enter into a partnership with NBCCF, the study must Be designed to answer an important, novel question relevant to breast cancer Be a well-designed clinical trial that is scientifically rigorous, employing appropriate and meaningful outcomes...

Function Basic

Although advocate roles and titles differ slightly from one cooperative group to another depending on the structure and specific needs of the group, their function is comparable from group to group. In all the cooperative groups patient advocates sit on and participate in disease committee activities, including discussion and comment on ideas and concepts presented to a committee, protocol development, conference calls, reviewing informed consent documents and committee decision making...

Q What advice is there for getting a protocol approved by the Institutional Animal Care and Use Committee in a timely

It should be obvious that completely answering all of the questions on the IACUC's application form is prerequisite to timely review and approval of an animal-use protocol. Given the IACUC's wide-ranging oversight of animal use, animal housing, personnel qualifications, veterinary care and (human) occupational health, an investigator may need to address a range of questions satisfactorily to obtain approval. The key to an acceptable and well-written animal protocol is for the scientist to...

Conclusion

In the war against cancer, industry must be a part of the coalition of the willing, and that poses an enormous set of challenges (Bodenheimer, 2000). Most specifically, the industry must be willing to invest in the shared infrastructure rather than to expect the public, through taxpayer dollars, to bear the full cost of a system that provides enormous benefits to the industry and its shareholders. In part, industry support must come in the form of monies paid into a joint public-private trust...

Partner with local patient networks

Sharing information about a clinical trial in your community with local patient networks is a good way to get the news out to your target population. This can be a member of your study team speaking to groups that have regular meetings, providing flyers or brochures for them to distribute, (*requires advance IRB approval) writing an article for their newsletter, informing 'hotline' volunteers (if they have one) about the study, or posting information about the study on the group's website (if...

Research Integrity And Scientific Misconduct

There is no subject that makes academicians more uncomfortable than scientific misconduct. This is not surprising. Just the allegation of a misdeed can seriously and adversely affect the career of a scientist, whether laboratory-based or clinical. A finding of misconduct can end any further opportunities for advancement, funding or even employment. Thus, there may be nothing more serious for an administrator than developing a system for handling such allegations in a fair, but confidential...

Accrual

An initial rationale for including advocates in the cooperative group system was help with increasing accrual to trials. Groups hoped that advocates would publicize open trials within the patient community. ACRIN advocates are doing exactly that placing significant emphasis on communicating to and through patient groups to inform patients about imaging clinical trials. Many patient advocate committees have links with patient support and advocacy groups through Internet communication,...

Create an information flyer or brochure

You may want to develop a flyer or brochure about a particular study that fits your local community. For instance, a story telling format would be an effective approach to Native Americans and a brochure in this format might increase chances of successful recruitment. Any materials developed at the local institution would require IRB approval before it can be disseminated, although materials developed independently by an advocate group does not. The education committee of ACOSOG also can - and...

Collgial challenges

Throughout the planning and conduct of a cancer clinical trial, the PI is involved with many different committees, organizations, and personnel (Figure 3). He or she is the leader of the team within the institution. The team may consist of co-investigators, nursing staff, cancer registrars, secretarial staff, residents, students, and volunteers. The PI represents the team when dealing with different institutions outside his or her own institution. These agencies are further discussed in...

Annual Reports

An IND sponsor must file within 60 days of the anniversary date that an IND went into effect an annual report to the FDA summarizing progress to date. The contents of an IND annual report to the FDA are outlined in 21CFR Subpart B Section 312.33 and include the following 7 components Individual study information- a brief summary of each study completed and those in progress including demographic information Summary information on all studies, both clinical and non-clinical, including integrated...

Later Phase Clinical Trials

Controlled, randomized phase 3 trials represent the gold standard in oncology and are required by the FDA for final approval of most new anticancer agents. To accomplish such trials, CTEP has sponsored a Cooperative Group program for the past 50 years that performs phase 3 trials utilizing new medical, surgical and radiation therapies, either alone or in combination. Multi-modality and specialty Groups (Figure 10) provide a unique, highly qualified, standing apparatus that permits the rapid...

Organization Of The

The FDA is organized into Centers based on the various regulated products. The FDA Centers are Center for Biologies Evaluation and Research (CBER) Center for Drug Evaluation and Research (CDER) Center for Devices and Radiologic Health (CDRH) Center for Food Safety and Nutrition (CFSAN) Center for Veterinary Medicine (CVM) National Center for Toxicologic Research (NCTR) Each product type has applicable laws and regulations. Overall FDA Operations and Policy are coordinated in the Office of the...

Challenges Facing The Approvals Program

The Commission on Cancer (CoC) Approvals Program serves as the nationally recognized body to approve cancer programs nationwide. Expectations for approval are described in the manual CoC Cancer Program Standards 2004. These standards define what is expected relative to each cancer program's prevention, early diagnosis, pretreatment evaluation, staging, optimal treatment, rehabilitation, surveillance for recurrent disease, support services, and end-of-life care. Among the requirements are cancer...

IND Filing

A sponsor must assume responsibility for the investigations and may be an individual or an organization. If the sponsor is an organization, there must be a designated point of contact within the organization. If an individual both initiates and conducts an investigation (21 CFR 312.3), the individual has the dual role of being a Sponsor-Investigator. This requires that the individual be attune to responsibilities designated to both sponsors and investigators (21 CFR...

Q How can animal pain be managed

The first step in animal pain management is prevention. To the extent possible, researchers should avoid procedures that could cause pain. After that, most acutely painful procedures should be performed under anesthesia, with appropriate post-procedural analgesia. Treatment of animal pain by pharmacologic means is similar to human pain treatment. Multimodal analgesia involves using medications of several different classes. For example, a surgery may include pretreatment with ketamine, local...

Support Systems For Regulatory Compliance

The task of navigating through this regulatory maze can be daunting to any physician investigator considering whether or not to initiate or participate in a cancer clinical trial. The issues confronting the physician investigator will vary depending on the type of cancer clinical trial involved. Those that arise as part of the complex and well-established cooperative group structure nurtured by the National Cancer Institute (NCI) of the U.S. National Institutes of Health (NIH) will be...

Q What do you have to submit to your IRB

A Most IRB's will require submission of a brief application in addition to the full protocol. In this application, you need to convey top the IRB the purpose of the research. Most IRB's distribute the main application to all the members, but only distribute the complete protocol to one or two members who serve as the primary reviewers. A clue to how they handle applications is how many copies are requested. Often the requirement will be for a large number of copies of the IRB application, but...

The Privacy Rule Hipaa As It Relates To Clinical Research

Falletta, MD Duke University Health System, Durham, NC, USA The U.S. Congress passed the Health Insurance Portability and Accountability Act (HIPAA) in 1996 to protect a worker's health insurance coverage as the worker changes employment, to reduce fraud, and to establish national standards for electronic healthcare transactions. Also reflected in HIPAA is a concern for the privacy of a person and the confidentiality of his her health information. The increase...

Acknowledgements

The development of a portion of the program described in this chapter was supported by grants S07 RR18240-01 and -02 from the National Institutes of Health. We would like to acknowledge the continuous and continuing support of the administration of The University of Texas M.D. Anderson Cancer Center (Presidents Drs. John Mendelsohn and Charles A. LeMaistre, Chief Academic Officers Drs. Margaret L. Kripke and Andrew von Eschenbach, and Vice President for Patient Care Dr. David Hohn) without...

Advocate To Explain Study Process Not Medical Information

As 'navigators,' Patient Advocates are sometimes seen as more approachable by patients, and are perceived as having more time to spend with the patient. Patients know the advocates have 'walked in their shoes' which is probably responsible for the high degree of trust they have in clinical trial information that comes from fellow patient groups. As collaborators with the clinical research team, navigators might provide information about the informed consent process, explain concepts like...

Assessments of audit findings

After all relevant information is reviewed the audit team makes an overall assessment of the research performance at the audited institution. Each of the three components (IRB informed consent, pharmacy and patient case review) is independently assessed and assigned a rating of Acceptable, Acceptable needing follow-up or Unacceptable. Standardized criteria for each rating are defined by the CTMB for use by all cooperative groups. Table 1. Rating criteria for IRB Informed consent and for Patient...

Background

The patient advocate collaboration with clinical researchers is unique in several ways and brings unique challenges for both advocate and clinician. A patient advocate usually enters this collaboration untrained in the language and concepts of clinical research. Historically the patient relationship with clinicians has been 'unequal,' the patient deferential to the clinician. Finally, s he might be dealing with advanced or metastatic disease - and sometimes dies. These factors influence how...

Basic ethical principles

The Belmont Report, issued in 1979, described fundamental ethical principles that should guide research involving human subjects. The Commission was charged specifically with providing guidance on (1) the boundaries between clinical practice and research (2) assessing risk and benefits as part of the process of reviewing human subject research (3) fair selection of subjects and (4) informed consent for research. Researchers and clinicians often have difficulty defining what constitutes research...

Components of an onsite audit

The objectives of an audit are to verify the study data submitted to the cooperative groups, and to verify compliance with the protocol as well as the regulatory requirements. Accordingly, the key components of an audit include 1. Assess compliance with research regulations by reviewing the Institutional Review Board (IRB) documentations and the informed consents of each protocol 2. verify accountability of investigational agents by reviewing pharmacy operations and records 3. evaluate protocol...

Conclusion And Recommendations

In conclusion, physician investigators who elect to participate in cancer clinical trials must be vigilant in their monitoring of the ever-changing regulatory compliance environment. It is important that they avail themselves and their staff of all opportunities for education, training and professional development in the courses focused on the ethical and responsible conduct of research involving human participants. Particular attention should be directed to the unique ethical and legal issues...

Conclusions

The CoC is able to continue serving the CoC-Approved Cancer Programs following enactment of a business associate agreement between each of the programs and the ACoS. Those worrisome unintended consequences, potentially threatening the value of a rich resource available to cancer patients, providers, and families, did not occur. The changes in the regulations, published in August 2002, were welcome relief to the CoC. Both the Approvals Program and the National Cancer Data Base (NCDB) were no...

CTSU Accrual Summary May 31 2005

1,000 900 800 700 600 500 400 300 200 100 NCI's cancer therapy evaluation program a commitment to treatment trials 49 Figure 13. CTSU Protocol History as of May 31, 2005 Cumulative number of protocols that have been active on the CTSU menu Cumulative number of protocols that have been active on the CTSU menu Figure 14. CTEP-sponsored Group trials contributing to FDA-approved pending primary or secondary indications for new agents Fludarabine phosphate (SWOG) Pentostatin (CALGB, SWOG) Paclitaxel...

Education

NBCCF's integrated strategy includes educational programs that inform advocates about all aspects of clinical trials. These programs help advocates understand all phases of the clinical trial process and enable them to prioritize and decide which clinical trials warrant their participation and or support. Educational materials also teach advocates how trials are designed and how to critically analyze trial data. NBCCF's clinical trial education programs address a comprehensive range of topics...

Establish federal requirements and guidelines for auditing programs

The primary responsibility of the CTMB is to establish federal guidelines for the monitoring of clinical trials, including those for quality assurance audits specifically. According to the CTMB, an audit program accomplishes the following objectives 1. to verify the study data relevant to the primary endpoints of the clinical trial through independent verification against source documents 2. to verify investigator compliance with the protocol and 3. to verify investigator and site compliance...

Export And Import Of Investigational Products

The regulation of exporting investigational products is determined by United States Federal laws and regulations and laws and regulations of the country or jurisdiction that is receiving the product. U.S. requirements for exporting an investigational product, as noted in the Code of Federal Regulations Title 21 Section 312.110, are the investigational product has an active IND each person receiving the product is an investigator named in the IND prior authorization from the FDA for use in a...

Fast Track

The Food and Drug Administration Modernization Act of 1997 (Public Law 105-115 Section 112) described a program intended to structure interactions between a sponsor and the FDA for INDs that meet certain criteria. The designation is granted for the combination of a product and a potential claim that would address a serious aspect of a serious or life threatening disease or condition that represents an unmet medical need. A request for Fast Track designation may be submitted at the time of the...

Followup and expected responses from institutions

After the submission of the final audit report to the CTMB, the institution is expected to submit a written response. This plan of action must address each specific area of major deficiency and non-compliance, covering each and every component rated as Acceptable Needing Follow-up or Unacceptable. Prior to submission, the proposed plan is typically communicated with the cooperative group within a few days for review. A finalized plan of action must be filed with the CTMB within 45 days after...

Historical Background

Research studies that involved serious ethical lapses have led to federal regulations and professional guidelines regarding the ethical conduct of research with human participants. During World War II, Nazi experiments intentionally inflicted serious harms on prisoners who gave no consent. In response to these atrocities, the Declaration of Helsinki of 1964 required consent from research subjects and established the need to balance the risks and benefits of the study.1 In 1972, news reports...

History Of Clinical Research

In 1966 Henry Beecher published a landmark article identifying at least 22 studies recently published in the medical literature that suggested serious ethical problems in the treatment of human subjects2 Beecher's, as well as other scientists' and journalists' revelations about the risks of research that emerged during the 1960s and early 1970s led to increasing calls for government regulation of research. In 1974 Congress passed the National Research Act. Title II of the Act created the...

Information Systems

Without the work capabilities gained through the use of modern computers, none of the functions described above could have been operational ized. Even the culture of an institution is altered when research teams have at their disposal, access to information about clinical research, the CFR, and IRB and institutional policies. What was once deemed impossible to track, now is readily at hand. That includes data and it also includes oversight of regulatory compliance. It is amazing how much better...

Institutional preparation for an onsite audit

The best preparation for an audit is performed prospectively. As protocols are activated and patients are enrolled, records should be meticulously kept, tracked and stored. Participating physician investigators should periodically review the performance of the research team, identify any problems and correct them internally.3'6 Prior to the scheduled audit, during the weeks after the institution is notified of the protocols and the patient cases to be audited, the institution should ensure that...

Invite advocates for discussion

The single most effective way to publicize a study is to create a partnership with patient advocates that will facilitate any of the other suggestions below. Partnering with Patient Advocates will pay dividends over time. They typically have extensive contacts with patient groups, they are highly motivated to 'make a difference' for other patients, and frequently have good ideas for improving procedures that are important to patients. Getting to know the local advocates 'up front' will enable...

Justice

The principle of justice requires that the researcher consider whether the risks and benefits of his or her proposed research are equitably distributed. True justice or fairness does not mean purely equal treatment. In medicine, public health and research there are well-accepted criteria for treating different individuals differently (e.g., only those with cancer ought to be considered candidates for chemotherapy, or only pregnant women need prenatal care), however it can often be difficult to...

Ongoing Trials

NBCCF has partnered on a number of clinical trials since initiating the collaborative model in 1996. In each case, they ensure that the most strategic and necessary questions are asked, and that trials include enough participants - with an equitable representation of the diverse patient population - to explore these questions effectively. And, to maintain a strident level of objectivity, NBCCF does not accept compensation from industry for any of its work on clinical trials. These trials...

Partnering With Patient Advocates At Your Local Institution

When thinking about launching a clinical trial in your community, consider creating partnerships with local Patient Advocates. Such partnerships can be advantageous for all concerned. As partners in clinical research, patient advocates can be a conduit for the flow of information between the medical community and the patient community. Consider this in a 2001 Harris Interactive Survey, 87 of patients said that they would very much or somewhat trust information about a trial which came from...

Q How will the experiment be monitored and ended

A The IRB will expect that there is independent oversight of the experiment. For minimal risk studies such as blood drawing only, minimal supervision is needed. For studies that represent higher risk often a Data Safety Monitoring Board (DSMB) is needed. It is imperative that you detail the stopping rules for the IRB. Stopping rules must cover most contingencies. It is unethical to continue the experiment when 1) there is no longer any possibility that there can be a positive result 2) the...

Q What alternatives are there for animal cancer studies

Following Russell and Burch's Principles of Humane Experimental Technique3, investigators consider three types of alternatives 1) Replacement alternatives refers to replacing vertebrate animals entirely, with cell or organ culture systems, microbiological models, invertebrate animals (such as Drosophila fruit flies), or computer models. Examples include production of monoclonal antibodies in tissue culture rather than in mouse ascites fluid, or using cell membrane extracts (liposomes) to...

Q What is your scientific rationale

A The IRB is primarily interested in deciding whether or not it is ethical to subject humans to the research you are proposing. The application must convince them that you are asking a valid question and that the experiment proposed has a reasonable likelihood of answering the question. You should not have to convince them that you are doing Nobel laureate work. In my opinion, it also not their function to decide what kind of research is carried out at your institution. The hospital or...

Q What regulations require Institutional Animal Care and Use Committees Are there exceptions

In the United States, two main bodies of regulation require IACUCs. The Animal Welfare Act (7 U.S.C. 2131 - 59 Title 9 Code of Federal Regulations) requires committee reviews for research using the animal species that law covers (currently, all mammals except laboratory-bred mice and rats), regardless of the source of funding for the research. Likewise, the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals requires committee review for projects at all...

Q What special review does vertebrate animal surgery require

A Regardless of the species, aseptic technique is required.14 (p. 62) Though oocyte collection is a major surgery (in that it penetrates a major body cavity), it may be performed on the laboratory bench in a clean area. Sterile instruments, proper skin disinfection, and use of sterile surgical gloves are the standard of care. The IACUC must review the qualifications and training of individuals who will perform surgery and anesthesia on a case-by-case basis. Specific degrees or certifications...

Scheduling of the onsite audit

The CTMB requires that the date of the scheduled audit be entered into the CTMB Audit Information System (AIS) at least six to ten weeks prior to the audit date. Therefore, institutions that are due for audits in the upcoming months are identified from the group membership roster several months ahead. The cooperative group audit team staff then contacts the responsible physician leader or main research staff at the institution to schedule a date for the audit. The date of the anticipated audit...

Scientific misconduct

Fraud or misconduct is difficult to define. According to the Policy on Responsible Conduct of Research (RCR) from the Office of Research Integrity, scientific misconduct encompasses the following elements 1) a significant departure from accepted practices of the relevant research community 2) the misconduct is committed intentionally, knowingly, or recklessly and 3) the allegation is proven by a preponderance of evidence.1 The reported frequency of scientific misconduct has been low. In 1993,...

Scope Of Interactions Between The Fda And Sponsors

An overview of the product development process along a time line is shown in Figure 1. The upper part of the time line notes the responsibilities of the product sponsor and the lower part of the time line notes the opportunities for interaction with and the responsibilities of the FDA that occur in parallel. Hash marks represent regulatory landmarks. The time line is hypothetical and follows a product through a 3 stage product development program with a marketing authorization granted and a...