A study conducted by the American Society of Clinical Oncology (ASCO) finds that different interpretations of the U.S. Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule can result in significant delays or abandonment of important clinical cancer research projects. The study also outlines measures that research sites can undertake to resolve these differences and speed the pace of research. The study results were published online today by the Journal of Clinical Oncology in an ASCO special article, “The Impact of the Privacy Rule on Cancer Research: Variations in Attitudes and Application of Regulatory Standards”.

The ASCO study examined differences in application of the HIPAA Privacy Rule between clinical researchers and compliance officers, who ensure that the site is complying with all regulatory requirements. While the interviews demonstrated that both research and compliance officials agree that patient’s cancer diagnoses should receive a high level of privacy protection, their interpretations of HIPAA compliance standards differed in some areas - both between interviewees at the same sites and from one site to another. Differing interpretations of the rule were seen most clearly in defining “future research use” of protected health information in tumor sample (biospecimen) and data repositories and the authorization waiver standards for disclosure.

Biospecimens have traditionally been widely used in cancer research. HIPAA instituted additional regulations regarding the use of these specimens with its implementation in of the Privacy Rule in 2003. However, in the years since its implementation, ASCO members have faced situations where the rule has slowed or even blocked certain types of studies that would benefit people with cancer and cancer survivors.

“ASCO is fully committed to protecting the privacy of people with cancer who participate in the clinical research process. However, we are concerned that a lack of clarity on the use and application of HIPAA privacy rules is causing unnecessary delays in important research,” said Richard L. Schilsky, MD, immediate ASCO Past-President and one of the study’s co-authors. “Biospecimen-based research is critical for advancing our efforts to develop personalized cancer care. To maximize our potential in cancer research, it is crucial that researchers and compliance officers are on the same page when it comes to the HIPAA Privacy Rule.”

ASCO’s Cancer Research Committee designed the qualitative research project using a team of three interviewers who spoke with 27 individuals (13 clinical researchers and 14 compliance officials) from 13 research sites. They were asked to describe how their sites would comply with the Privacy Rule in three hypothetical research studies. The scenarios focused on studies of cancer survivors, familial cancer syndromes and creation and use of data biospecimen repositories.

In the conclusion, ASCO proposes several strategies to resolve differing interpretations of HIPAA, including ongoing institutional training programs to improve communication among researchers and compliance officials on HIPAA-related issues and developments. ASCO also recommends developing case-study based federal guidance documents and cancer-specific model practices documents to guide creation of data repositories, disclosure and use of data from these repositories, and the design of survivorship and genetics studies.

In addition to the recommendations of the study, ASCO is also pursuing changes to HIPAA to allow for use of biospecimens in future cancer research. The Department of Health and Human Services Office for Civil Rights (which administers HIPAA) will be making modifications to the Privacy Rule as a result of provisions of the American Recovery and Reinvestment Act of 2009. ASCO sent a letter to the Office of Civil Rights encouraging the agency to use this as an opportunity to clarify the “future research use provisions.”

“In my experience, patients and families generally want to participate in research because they realize the potential benefits for them and future cancer patients. It is very frustrating that inefficient and ineffective policies get in the way of a genuine willingness to be involved,” said Michael Link, MD, immediate past chair of ASCO’s Cancer Research Committee.

This project was limited by the three design issues that may affect the ability to generalize the findings. The issues are: (1) the limited number of sites; (2) the fact that the compliance officials at each institution may have slightly different perspectives on compliance; and (3) convenience sampling of sites conducting cancer research studies. Despite these limitations, data from the interviews revealed consistent themes.

Source
American Society of Clinical Oncology

Expression of a single gene programs an immune system helper T cell that fuels rapid growth and diversification of antibodies in a cellular structure implicated in autoimmune diseases and development of B cell lymphoma, scientists at The University of Texas M. D. Anderson Cancer Center reported today in Science Express, the advance online publication of the journal Science.

The gene is Bcl6, which the team found plays the crucial role in differentiating a naïve T cell into a T follicular helper cell (Tfh).

“Tfh cells were first noticed in structures called germinal centers found in the lymphoid system - in lymph nodes and the spleen,” said senior author Chen Dong, Ph.D., professor in M. D. Anderson’s Department of Immunology. Germinal centers are powerful machines that churn out lots of antibodies.

In the adaptive immune system, B cells present an antigen - a distinctive piece of an invading bacterium or virus - to T cells. The bound antigen converts a naïve T cell to a helper T cell that secretes cytokines which help the B cells expand and produce a large volume of antibodies to destroy an intruder.

Tfh cells are concentrated with B cells in germinal centers, where they play a helper T cell’s traditional role in B cell proliferation and antibody development.

“In germinal centers, the B cells not only proliferate but they also undergo hypermutation in their immunoglobulin genes so they can produce a diverse class of antibodies,” Dong said. “These mutations also allow production of antibodies with stronger affinity for their target antigens.”

There are pitfalls to this process. Tfh cells and germinal centers have been implicated in antibody-mediated autoimmune diseases such as lupus and rheumatoid arthritis, Dong noted. In these diseases, the germinal centers are likely producing the wrong type of antibody at great volume.

Genetic hypermutation among B cells in germinal centers creates a hotbed of genomic instability, which gives rise to some types of B cell lymphoma, Dong said.

The scientists set out to understand the role of Bcl6, which is short for B-cell lymphoma 6, a transcription factor previously shown to be selectively expressed in Tfh cells.

Last year, Dong and his colleagues reported in the journal Immunity that cytokines IL-6 and IL-21 drive the differentiation of Tfh cells. However, how these cytokines work had been unclear. In the current study, the team reported that that IL-6 and IL-21 induce expression of Bcl6 in the absence of transforming growth factor beta (TGFß) to drive T cell differentiation into Tfh. “Not only is Bcl6 a transcription factor expressed by Tfh cells, it also has a major function in generating these cells,” Dong said.

When TGFß is present with IL-6 and IL-21, T cells differentiate into pro-inflammatory Th17 helper cells.

Another set of experiments showed that Bcl6 expression inhibits a T cell from differentiating into Th17, Th1 or Th2 cells, three other lines of helper cell

Finally, when the Bcl6 gene was knocked out in a mouse model, Tfh was nowhere to be found. “Bcl6 is absolutely required for Tfh generation and it’s also important because it blocks other pathways that would lead the T cell into other helper cell types,” Dong said.

Solving the molecular programming of Tfh establishes it as the fifth distinct lineage of helper T cell.

Dong and colleagues will continue to characterize Tfh and its relationship to other T helper cells. Dong is co-discoverer of the Th17 cell, which he and colleagues identified as the third T helper cell lineage when conventional wisdom held that there were only two such lines. They also showed that Th17 secretes interleukin-17, which is implicated in both inflammatory and autoimmune diseases.

ACCESS PHARMACEUTICALS, INC. (OTC Bulletin Board: ACCP), announced that its European partner, SpePharm, is collecting data from a post approval study of MuGard in head and neck cancer patients undergoing radiation treatment in the UK showing prevention of oral mucositis. In a multi-center study expected to enroll a total of 280 patients, patients are provided with seven weeks of MuGard therapy, and begin using MuGard one week prior to radiation treatment and then throughout the subsequent six weeks of planned therapy. The first 140 patients being treated in this assessment study have been enrolled and treated, and as of the time of the update, none of these patients have experienced any oral mucositis.

“The initial feedback from SpePharm on their experience in the UK, with the first 140 patients in the assessment study, exceeds our most positive expectations,” stated Jeffrey B. Davis, Access’ President & CEO. “Normally, roughly 100% of patients undergoing radiation treatment for head and neck cancer experience some level of oral mucositis. This condition varies from a low level of discomfort and pain, up to Grades 3 and 4 which are debilitating to the point of patients discontinuing therapy. To see a result where all or substantially all of the patients using MuGard, and using it prophylactically, are not getting oral mucositis is extremely important with respect to treatment regimens. We believe the final data set will show that MuGard should be used prophylactically with all radiation or chemotherapy regimens that have the potential to lead to oral mucositis, greatly expanding the target market.”

MuGard is a novel, ready-to-use mucoadhesive oral wound rinse for the management of oral mucositis, a debilitating side effect of many anticancer treatments. Up to 40% of all patients receiving chemotherapy and/or radiotherapy develop moderate to severe mucositis, and almost all patients receiving radiotherapy for head and neck cancer and those undergoing stem cell transplantation develop mucositis. Updated clinical practice guidelines for the prevention and treatment of mucositis recommend the use of a preventive oral care regimen as part of routine supportive care along with a therapeutic oral care regimen if mucositis develops. The market for the treatment of oral mucositis, used prophylactically for patients undergoing chemotherapy and radiation therapy, is estimated to be in excess of $5 billion world-wide.

MuGard forms a protective coating over the oral mucosa when swirled gently around the mouth. In a comparison of cancer patients receiving standard mucositis care with those patients receiving MuGard, the incidence and severity of mucositis was significantly lower in the MuGard treated group using a validated scale for the assessment of oral mucositis.

About Access:

Access Pharmaceuticals, Inc. is an emerging biopharmaceutical company that develops and commercializes propriety products for the treatment and supportive care of cancer patients. Access’ products include ProLindac(TM), currently in Phase 2 clinical testing of patients with ovarian cancer, and MuGard(TM) for the management of patients with mucositis. The company also has other advanced drug delivery technologies including Cobalamin(TM)-mediated targeted delivery and oral drug delivery, its proprietary nanopolymer delivery technology based on the natural vitamin B12 uptake mechanism; Angiolix(R), a humanized monoclonal antibody which acts as an anti-angiogenesis factor and is targeted to breast cancer; and Thiarabine, a new generation nucleoside analog which has demonstrated both pre-clinical and clinical activity in certain cancers.

This press release contains certain statements that are forward-looking within the meaning of Section 27a of the Securities Act of 1933, as amended, and that involve risks and uncertainties. These statements include those relating to: clinical trial plans and timelines and clinical results for ProLindac and product candidates acquired in the MacroChem transaction, our ability to execute licensing agreements in the future, Access’ plans to continue and initiate clinical trials, the value of its products in the market (including MuGard and the size of the overall market for mucositis products), its ability to achieve clinical and commercial success and its ability to successfully develop marketed products. These statements are subject to numerous risks, including but not limited Access’ need to obtain additional financing in order to continue the clinical trial and operations and to the risks detailed in Access’ Annual Reports on Form 10-K and other reports filed by Access with the Securities and Exchange Commission.

Source: Access Pharmaceuticals, Inc