Online First/Online Only
Articles/items published ahead of print or only online.
Friday, March 07, 2014
BY SARAH DIGIULIO
A new report from the American Cancer Society estimates that among U.S. children and adolescents (age 19 and younger), 15,780 new cases of cancer will be diagnosed this year and 1,980 deaths from cancer will occur.
The article, now available online ahead of print in CA: A Cancer Journal for Clinicians (DOI: 10.3322/caac.21219), and also disseminated as a Special Section of the Society’s “Cancer Facts & Figures 2014” (cancer.org/statistics), summarizes the most recent and comprehensive data on cancer incidence, mortality, and survival from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries.
“We’ve been frustrated with the aggregated numbers because they don’t tell the full picture of where we’re making progress and where we still have shortfalls,” Rebecca Kirch, the ACS’s Director of Quality of Life and Survivorship and Cancer Control and an editor of the report, explained in an interview.
“This report is intended as a roadmap to help prioritize where extra attention needs to be paid for cancers that haven’t seen progress. It is essential to help us plan out and prioritize the research agenda and the advocacy agenda—so that we can develop better clinical outcomes, both in terms of cure rates and quality of life measures.”
She noted that although ACS’s annual report always includes data on childhood and adolescent cancer survivors, this is the first report in approximately a decade to include incidence and mortality rates broken down by cancer subtype, as well as information about these survivors’ long-term and late effects from treatments.
“Progress in childhood cancer has been dramatic for some sites, but we cannot let that blind us from the fact that progress has been disappointingly slow for other sites, and that cancer remains the second leading cause of death in children,” Otis W. Brawley, MD, the ACS’s Chief Medical Officer, said in a news release. “There is much work to be done to improve outcomes, to reduce side effects, and, we hope, to understand more about the molecular events that lead to childhood cancer in order to come up with ways to prevent or detect it early.”
Key statistics and findings from the report are the following:
The annual incidence of cancer from birth to age 19 is 18.8 per 100,000 individuals;
Approximately one in 285 children will be diagnosed with cancer before age 20;
Today about one in 530 young adults between age 20 and 39 is a childhood cancer survivor;
The most common cancers in children 14 and younger are acute lymphocytic leukemia (26%), brain and central nervous system (CNS) cancers (21%), neuroblastoma (7%), and non-Hodgkin lymphoma (6%);
The most common cancers in children 15 to 19 are Hodgkin lymphoma (15%), thyroid carcinoma (11%), brain and CNS cancers (10%), and non-Hodgkin lymphoma (6%);
Non-Hispanic white (white) and Hispanic children have the highest incidence rates for childhood and adolescent cancers;
Although incidence rates are substantially lower for non-Hispanic black (African American) children and adolescents than for whites and Hispanics, death rates are similar due to lower survival rates in African Americans;
The overall incidence of pediatric cancer in the U.S. from 1975 to 2010 increased by an average of 0.6 percent per year, with incidence rates increasing specifically for four cancer types (acute lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin lymphoma, and testicular germ cell tumors);
Incidence rates decreased for Hodgkin lymphoma and remained stable for other cancers;
Overall five-year survival rates across all cancer sites increased from 63 percent between 1975 and 1979, to 83 percent between 2003 and 2009; and
Death rates for all childhood and adolescent cancers combined steadily declined from 1975 to 2010 by an average of 2.1 percent per year (resulting in an overall decline in mortality of more than 50%).
The report includes additional information on risk factors, symptoms, treatment, and long-term and late effects for the most common cancers types in children and adolescents by site. Data in the report also show that some cancers still do remain deadly, such as diffuse intrinsic pontine glioma—for which the median survival time after diagnosis is less than one year, Kirch added. “We have no available treatment—nothing we can do.”
Other challenges detailed in the report are that only a small proportion of childhood cancers have known or preventable causes; and early diagnosis of cancer in children is often difficult because of the similarity of symptoms to more common diseases in children. The clinical scene for children and adolescents with cancer looks very different than it does for adults—from diagnosis onward, Kirch said. “We don’t have a lot of information yet about what’s causing some of these cancers. And, we don’t have screening tools for the types of cancers that kids get like we do for adults.”
Another challenge: Even though advances in survival have been made for many types of cancers, many children treated for cancer still have high risks of long-term health issues associated with treatment (see OT’s coverage of unmet survivorship needs of childhood cancer survivors in the 9/25/13 issue).
In acute lymphocytic leukemia there has been progress in treatment and improvements in cure rates, but emerging literature shows that long-term side effects are still problematic for these patients, Kirch explained. “The toxicities of our treatment are a significant concern. We still need to make sure people’s lives, across the life course, are pain- and symptom-free to the extent that is possible.”
Remembering the 17%
Asked to comment about the report for this article, Leslie L. Robison, PhD, Chair of the Department of Epidemiology and Cancer Control and Associate Director for Cancer Prevention and Control at St. Jude Children’s Research Hospital, noted that the report highlights the improvements in survival rates for childhood and adolescent patients with cancer in the past four decades. “But, it is important to also focus on the work that remains to cure the other 17 percent of patients [the report notes the overall survival rate across all cancers for this patient population is 83%], and to understand the long-term consequences of treatment in the cured population who have 60 to 70 years of life ahead of them.”
LESLIE L. ROBISON, PHD
Another key take from the report, he added, is the need for prevention research: “This report emphasizes—after decades of research—how little we know about the causes of the cancers that occur in this young population.”
Thursday, March 06, 2014
BY KURT SAMSON
Two premalignant abnormalities on breast biopsies that for decades have been viewed as having very different behaviors appear to have the same long-term cancer potential and progression risk, according to new data from researchers at the Mayo Clinic.
It is generally believed that atypical ductal hyperplasia (ADH) is a direct precursor of breast cancer and therefore portends breast cancer in the same breast, while atypical lobular hyperplasia (ALH) has an equal risk of cancer in both breasts and may not be a direct precursor of breast cancer. In the study, however, published in Cancer Prevention Research (2014;7;211-217) and led by
Lynn C. Hartmann, MD, Professor of Oncology, cancer was twice as likely to occur in the breast having the biopsy, and this was true for both ADH and ALH.
Moreover, the findings run counter to current understanding that ALH primarily leads to lobular cancer. Instead, the researchers discovered that ALH was associated predominantly with later ductal cancers of the breast -- also similar to cancers after ADH.
Both types resulted in invasive ductal cancers, and 69 percent were of intermediate or high grade. Further, about 25 percent had spread to the lymph nodes. Although the numbers were not statistically significant, the study also found that more ductal cancer in situ occurred following ADH than after ALH – 25 percent versus 13 percent. In addition, women with ADH were more likely to have an ipsilateral breast cancer in the first five years after diagnosis than in later years.
The study included 698 women with biopsies showing atypical hyperplasia: 330 with ADH, 327 with ALH, and 32 with both types. Over an average follow-up of 12.5 years, 143 women developed breast cancer, but at the same rates regardless of the type of atypia. And in confirmation of the high-risk nature of atypia, 29 percent of these women developed breast cancer by 25 years of follow up.
“Our observations do not support present assumptions that ADH and ALH have substantively different behaviors,” Hartmann said. “Ours is the first report with sufficient numbers of both types of atypia and long-term follow-up that was able to examine the type of subsequent breast cancer, when these occurred, and in which breast.
“We showed that even though the two types of atypia look different histologically, they behave quite similarly in terms of later breast cancers in patients.”
Importantly, she added, many have believed that women who have both atypia and a positive family history of breast cancer have a risk that is substantially higher than that of someone with atypia without a family history.
“In our large study of women with atypia, we compared the later breast cancer risk of 257 women who had a family history and 372 without a family history, and saw no difference in their later risk. How can this be? In fact, one cause for the development of atypia is having a family history – so the risk associated with family history is already accounted for by the presence of the atypia itself.
Better Risk Assessment
More than one million women undergoing a breast biopsy in the United States each year have benign findings, and about 10 percent of these biopsies reveal atypical hyperplasia, a premalignant finding with a proliferation of abnormal cells, which have some but not all the features of a breast cancer.
“Most clinicians have viewed ADH as a direct precursor to breast cancer, arguing that it requires complete surgical excision, while others have maintained that ALH serves as an indicator of heightened and equal risk of breast cancer across both breasts,” Hartmann explained.
“Whether or not ALH on a core biopsy requires surgical excision remains a topic of research investigation. Moreover, some experts have argued that women with atypia develop ‘better risk’ breast cancers -- meaning low-grade cancers with a good prognosis.”
Improve Clinical Management
Findings from this study could improve clinical management of patients with breast tissue abnormalities, she said.
“Given the high-risk nature of atypia, with a risk of breast cancer of close to 30 percent at 25 years after biopsy, we recommend that such women be seen at a breast center for recommendations about surveillance and preventive therapy options.
“What we are providing is absolute risk data for a sizable cohort of women with atypia. The medical community has known for years that the relative risk of breast cancer for women with atypia is four times greater than for other women, but that does not translate into an actual number for an individual with abnormal biopsy findings. Hopefully our paper will raise awareness of the risk and encourage the most sophisticated surveillance, likely to include MRI screening, and the use of chemoprevention drugs such as tamoxifen.”
Many practitioners already encourage women with atypia to consider chemoprevention drugs, she added.
“I think that women are increasingly aware that these are options, but nevertheless, many women remain more concerned about the possible side effects associated with these agents. They also need good data about the breast cancer risks.”
She and her colleagues are now preparing a review article that may help to guide development of new guidelines reflecting their findings, she said.
Asked for his opinion for this article,
Stuart J. Schnitt, MD, Professor of Pathology at Harvard Medical School and Director of Anatomic Pathology at Beth Israel Deaconess Medical Center, said some of the observations in this study confirm data from previous reports but that there are also new data that add to what is understood about atypical hyperplasia.
In a 2007 study published in Cancer (2007;109:180-187), he and his colleagues (first author was Laura C. Collins, MD) analyzed the magnitude and laterality of breast cancer risk based on the histologic type of atypical hyperplasia among women in the Nurses’ Health Study. Like the Mayo group, they found that about 60 percent of subsequent cancers occurred in the ipsilateral breast. However, that study also suggested that the risk associated with ADH and ALH depended upon the menopausal status of the patient at the time of the benign breast biopsy, something that was not addressed in the Mayo study.
In addition, in a 2003 study in The Lancet (2003;361:125-129), researchers at Vanderbilt University, led by David L. Page, MD, looked at ALH as a unilateral predictor of breast cancer risk in 250 women in the Nashville Breast Cancer Studies cohort.
Schnitt noted that comparisons among these studies is somewhat difficult since the Nurses’ Health Study benign breast disease analysis was based on a nested case-control study whereas the Mayo and Vanderbilt studies are cohort studies. “Nonetheless, despite the methodologic differences in these three studies, there are many similarities in the findings regarding atypical hyperplasias,” he said.
“We now recognize that both ADH and ALH are associated with a substantially increased risk of breast cancer, that both lesions appear to represent direct cancer precursors as well as markers of increased risk. I think the similarities rather than the differences between ADH and ALH is one of the main take-home messages from the Mayo study. The time has come to find ways to better stratify risk and identify which women with atypical hyperplasia are at highest risk.”
And, although treatment and monitoring guidelines from the American Society of Clinical Oncology or the American Cancer Society would be helpful, the extant data are not sufficiently robust to permit consensus guideline recommendations, he said.
“Guidelines need to be evidence-based, and the available evidence from individual studies is based on very small numbers in some subgroups. Perhaps attempting to combine data from the Nurses’ Health Study, the Vanderbilt Study, and the Mayo Clinic study would be a worthwhile undertaking and provide more statistical power than any of these studies alone.”
Tuesday, March 04, 2014
The U.S. Food and Drug Administration has granted orphan drug designation to Pracinostat for the treatment of acute myeloid leukemia. The investigational drug is an oral histone deacetylase (HDAC) inhibitor, and has so far demonstrated evidence of single-agent activity in elderly AML patients in a Phase I dose-escalation trial.
The Orphan Drug designation—to encourage development of drugs in the diagnosis, prevention, or treatment of a medical condition affecting fewer than 200,000 people in the U.S.—grants a product market exclusivity for a seven-year period if the sponsor complies with certain FDA specifications, as well as tax credits and prescription drug user fee waivers. The designation does not, though, shorten the duration of the regulatory review and approval process.
About 18,860 new cases of AML are expected to be diagnosed this year, according to estimates from the American Cancer Society. The average age at diagnosis is 66.
Pracinostat has been tested in Phase I and II clinical trials in advanced hematologic disorders, as well as in solid tumors in both adult and pediatric patients—having been generally well tolerated in more than 200 patients, with manageable side effects, common to similar drugs. The drug is also currently being tested in Phase II trials in combination with Vidaza (azacitidine) for the treatment of newly diagnosed AML in elderly patients.
Pracinostat is marketed by MEI Pharma, Inc.
Tuesday, March 04, 2014
By Peggy Eastman
WASHINGTON -- As Congress debates physician payment reform legislation, speakers at a meeting here emphasized that whatever form this reform effort takes, it must be truly patient-centered to improve individualized care. Presenters at the meeting, co-hosted by the National Coalition for Cancer Survivorship (NCCS) and the American Enterprise Institute (AEI), cited the Institute of Medicine’s comprehensive 2013 report calling U.S. cancer care “a system in crisis,” and explored how new payment methods could address that crisis and enhance cancer care.
The SGR Repeal and Medicare Provider Payment Modernization Act of 2014 now before Congress is a reform initiative that has bipartisan, bicameral support. The legislative package would repeal the Medicare sustainable growth rate (SGR) formula that governs growth in Medicare spending and move Medicare away from a fee-for-service system. The SGR would be replaced with a merit-based incentive payment system for physicians who meet certain standards, and encourage health professionals to design and test alternative payment models.
“Is there a crisis? Yes, there is,” said Michael Kolodziej, MD, of Aetna, where he is National Medical Director for Oncology Solutions in the office of the chief medical officer. “Oncology care today is just not good enough; it’s got to be better. The SGR is the sword of Damocles hanging over every doctor who treats cancer patients.”
‘Major Payment Problems in Cancer’
“I think it’s safe to say there are major payment problems in cancer,” said Joshua M. Sharfstein, MD, Secretary of the Maryland Department of Health and Mental Hygiene, former principal deputy commissioner of the Food and Drug Administration, and former commissioner of health for the city of Baltimore. “The way chemotherapy is reimbursed does not make any sense. There are enormous gaps in prevention of cancer and many patients run out of treatment options. What makes this especially frustrating is that there so much scientific progress in cancer.”
NCCS CEO Shelley Fuld Nasso said that the organization supports current Medicare payment reforms, believing that the changes will lead to better patient cancer care planning, clinical coordination, and shared decision-making. “But we do need patients at the table when these discussions on reform take place” to ensure that payment reform models are indeed patient-centered,” she emphasized.
The NCCS, an active policy participant, has supported IOM initiatives to identify weaknesses in U.S. cancer and survivorship care, worked to secure Medicare coverage for the routine patient costs incurred in cancer clinical trials, and advocated provisions in the Affordable Care Act to ensure access to health care for cancer survivors.
“I think it really all comes down to the steps that all of us can take to improve care,” said Mark McClellan, MD, PhD, Senior Fellow and Director of the Health Care Innovation and Value Initiative at the Brookings Institution. “We’re seeing a lot of movement away from fee for service; fee for service just isn’t very well suited to the kind of personalized medicine cancer patients need,” added McClellan, a former administrator of the Centers for Medicare & Medicaid Services (CMS) and a former FDA commissioner.
New Level of Optimism
Also at the meeting, Rep. Tom Price, MD (R-GA), said he is optimistic that the current payment reform legislation will become law. “There’s been a level of cooperation that we haven’t seen in a long time,” said Price, an orthopedic surgeon. “I’m hopeful and mildly optimistic… When you have that kind of unanimity it’s important to embrace the opportunity.
“It’s absolutely vital to have physician leadership on this,” he added. “There are a lot of doctors who have gotten incredibly frustrated with the current system, and understandably so.” These physicians, he said, are saying “Thanks for the memories; I’m moving on.” Their loss to medicine when they do move on represents a “huge intellectual capital loss,” since these physicians are the ones with the most clinical experience and a high level of skill.
Oncology Medical Home
McClellan cited the oncology medical home as a promising new model of personalized cancer care. Agreeing was John Sprandio, MD, Chief of Medical Oncology and Hematology at Delaware County Memorial Hospital, Director of the Delaware County Regional Cancer Center, a member of the Fox Chase Network and the CMS Oncology Payment Reform Technical Expert Panel, and founder and managing partner of Oncology Management Services Inc.
“I really do believe that cancer care is in crisis, and it’s pretty late in the game,” said Sprandio, who has pioneered the oncology patient-centered medical home, a cancer care model that combines high-quality, evidence-based patient-centered care with new technology with the aim of creating efficiency, coordinating care, enhancing communication within the patient’s care team, and reducing unnecessary use of health resources.
He said that despite the crisis in cancer care identified by the IOM, he remains optimistic because of payment reform: “Now is the time to do it [payment reform], and do it quickly… to make sure patients are cared for adequately.”
Sprandio noted that the oncology patient-centered medical home (OPCMH) model standardizes the process of cancer care on a foundation of evidence-based guidelines and that “standardization of process acts as a patient safety net--these standards drive consistency.”
Asked in an interview if professional medical societies support the OPCMH concept, Sprandio said, “All the professional societies get it. The biggest barrier would be to get payers to embrace this process.”
Because it is a new concept of care, payers have taken a while to accept the OPCMH, he said, stressing that the model “is reproducible by any practice, and that changes can be made in process regardless of the infrastructure of the practice.”
Sprandio recommended that members of an oncology practice who want to adopt the OPCMH model start with the National Committee for Quality Assurance (NCQA); his oncology practice was the first specialty practice to be recognized by NCQA as a level III patient-centered medical home.
‘Larger and Larger Out-of-Pocket Costs’
He as well as others at the meeting called Medicare physician payment reform necessary for cancer patients in part because patients are being asked to shoulder larger and larger out-of-pocket costs for their drugs. “Patients are now making decisions not to be treated because of these costs; I can’t tell you how distressing it is,” Sprandio said.
Peter Ubel, MD, Professor of Marketing in the Fuqua School of Business and Professor of Public Policy in the Sanford School of Public Policy at Duke University, said, “It doesn’t take much before the cost to the patient is catastrophic.” He cited the case of a truck driver with metastatic colorectal cancer who could no longer afford his chemotherapy treatments – a case that is not unusual today.
Any alternative payment models should recognize that “cancer care is a team sport,” said John Cox, MD, a medical staff member of Methodist Hospitals of Dallas (where he is past president of the medical staff) and Editor-in-Chief of the Journal of Oncology Practice. “We’ve got to develop more of a team approach, and we need a reimbursement system that honors the team.”
Asked by OT if patient-centered alternative payment models could help to respect and carry out cancer patients’ wishes about end-of-life care, Cox said yes. “Process standardization is a way of ensuring that end-of-life discussions can occur. When a patient has metastatic cancer, there ought to be a clear discussion of the goals of care in the beginning. In our practice, that has been a challenge: just to have that conversation.”
Cox noted that it is difficult for many physicians to communicate to patients with advanced cancer that they are on a journey that ultimately will take their lives. This kind of communication “is a skill,” he said, adding, “I think we tend to underplay this at our meetings.”
Agreeing with Cox on the need for alternative payment models that include patient-centered discussions on end-of-life care was Lillian Schockney, RN, Administrative Director of the Johns Hopkins Breast Center, Director of the Johns Hopkins Cancer Survivorship programs, Editor-in-Chief of the Journal of Oncology Navigation and Survivorship, founder and program director of the Academy of Oncology Nurse Navigators, and a two-time breast cancer survivor. “It does not take away patients’ hope; they may transition to alternative hopes,” she said, such as planning to attend a wedding or living to see the birth of a grandchild.
Some patients with advanced cancer may be undergoing care not because they want it, but because a close family members wants them to have it, she noted. “We need to know our patients well beyond their pathology. We still tend to treat for treatment’s sake.”
As for whether physician payment reform will become a reality this year, Rep. Price said, “I wish I could tell you.” Added Kolodziej, “I think we can do it if we put our minds to it.” Asked by OT at the end of the meeting if they were pleased by the presentations and discussion, Nasso and NCCS Senior Health Policy Advisor Ellen Stovall both said yes. Noted Stovall, “There are a lot of things we need to follow up on, especially in the payment area.”
Sunday, March 02, 2014
BY PEGGY EASTMAN
WASHINGTON -- As cancer clinical trials have become larger and more complex and potentially sensitive patient genomic analyses more common, issues of protecting the privacy and rights of participants in those trials have become more challenging – issues that were explored at a scientific workshop here hosted by the National Cancer Policy Forum (NCPF) of the Institute of Medicine.
Federal regulations such as the Common Rule and the Health Insurance Portability and Accountability Act (HIPAA), which was recently modified, protect the privacy of individually identifiable health information. So do the rules of local institutional review boards (IRBs). But, in an era of massive computerized data collection and increased data sharing to advance scientific knowledge, thorny questions about privacy, rights, and informed consent have arisen. IOM workshop speakers examined many of those issues in detail, and the Institute expects to publish a written summary of their deliberations in about six months.
The current landscape for clinical trial investigators presents “a conundrum,” said NCPF member Richard L. Schilsky, MD, Chief Medical Officer of the American Society of Clinical Oncology and former Chairman of Cancer and Leukemia Group B. Patients’ clear right to privacy must be balanced against the vision of a continuous learning system in health care, embraced by both ASCO and the IOM, he noted, pointing out that “you can’t do much learning” if new information observed in clinical trials cannot be disclosed.
“IRBs are extremely conservative, by and large. IRBs should become advocates for responsible research -- not obstacles.” He added, “I’m of the opinion that we spend a lot of time protecting people from things they don’t want to be protected from.”
Another speaker, NCPF Vice Chair Patricia A. Ganz, MD, agreed on the need to balance patient protections with the need for a continuous learning environment in cancer clinical trials and cancer care: “Truly we do need a reset to improve the whole clinical research enterprise; I think we would want every patient potentially to be a research subject,” said Ganz, Distinguished University Professor at the Fielding School of Public Health and Director of Cancer Prevention & Control at UCLA’s Jonsson Comprehensive Cancer Center.
Ganz, who moderated a workshop session, chaired the IOM committee that last year published the sweeping 384-page “Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis” report (OT 10/10/13 issue).
Today, protections for cancer patients are becoming more complicated in part because the line between clinical research and care is often blurred, said Angela Bradbury, MD, Co-chair of the IOM workshop planning committee and Assistant Professor in the Division of Hematology-Oncology at the University of Pennsylvania. “Research and clinical care are often intertwined in oncology,” blurring heightened by electronic medical records, she said.
Several speakers described the general willingness of clinical trial participants who signed an initial consent form, especially those who are older, to have their data and/or biospecimens used in future research trials to find cures for cancer. “By the time you’re 90, you’ve gotten the diseases you’re going to get,” said Gail Jarvik, MD, PhD, holder of the Arno G. Motulsky Endowed Chair in Medicine and Head of the Division of Medical Genetics at the University of Washington School of Medicine. “The older people just want the problem fixed.”
All the speakers agreed on the need for strong patient privacy protections regardless of subjects’ desire to participate in trials, especially in an era of high-profile massive security data breeches. “The sickest people tend to be the most vulnerable… there has to be something in place to protect the most vulnerable,” said Alice Leiter, Policy Counsel for the Center for Democracy & Technology’s Health Privacy Project.
While data security breeches have not plagued clinical trial research, in today’s era of electronic communication and storage, no database is entirely secure, warned Bradley Malin, PhD, Vice Chair for Research and Associate Professor of Biomedical Informatics at Vanderbilt University School of Medicine. “Given enough effort, you can break into any system… I don’t care what people tell you.”
He noted that HIPAA regulations specifically require that collected health information cannot be used to identify an individual, and discussed BioVu, a privacy-protection research repository developed at Vanderbilt of DNA extracted from discarded blood collected during routine clinical testing and linked to de-identified electronic medical records. The goal is to provide a resource to Vanderbilt investigators for studies of genotype-phenotype associations.
In developing BioVu, there were a lot of challenges, he said, pointing out that de-identification of patient information is especially difficult when it is taken from physicians’ notes. But, he noted, in “scrubbing” trial participant data, such facts as race and age can be obscured, and geographical areas can be “coarsened.” For example, such terms as “North America” and “Eastern Europe” can be used instead of specific place names.
The clinical trials consent form remains a mainstay of patient protection. Mary McCabe, RN, MA, Director of the Cancer Survivorship Program at Memorial Sloan-Kettering Cancer Center and a previous NCI staff member, described how in 1997, the NCI launched an initiative to improve the consent form for clinical trials. Patient advocacy groups wanted change, and even IRB groups were questioning the length and complexity of the documents.
Although the NCI initiative did produce an updated informed-consent template in February 2013 for use in clinical research trials, there is still room for improvement, speakers said. While the new template is more patient-centered, “the document remains too long and overwhelming, and the reading level is still too high,” said Laura Cleveland, Co-Chair of the Patient Advocate Committee of CALGB/Alliance.
While agreeing that a consent form is just one component of patient protection, speakers discussed in detail how to improve the consent form as part of the overall process of enrolling a clinical trial subject. Virtually all speakers agreed with Cleveland that consent forms are still too long, too complicated, too full of medical jargon, and written on too high a reading level – points that she showed vividly in her presentation.
Federal statutes mandate that IRBs ensure that informed-consent standards be written in language lay people can understand, noted Michael Paasche-Orlow, MD, MA, MPH, Associate Professor of Medicine at Boston University School of Medicine. But, he said, the average reading level in the United States is grade eight or nine – “and there is a huge relationship between educational attainment and literacy. So if you don’t check, you don’t know what the person understands when reading a consent form.”
Paasche-Orlow, who is studying interactive computerized models to improve comprehension of consent forms, recommended that clinical trial investigators “require confirmation of comprehension as an entry criterion” into a study. They can ask potential trial participants, for example, questions such as: “Tell me the goal of this research and what will happen to you if you participate.”
‘Opportunity for Professional Development’
There is a lack now of trained professional adult educators who could explain consent forms to potential clinical trial participants. “This is an opportunity for professional development,” he said. “We need a model training program for informed consent,” which, he predicted, “could shift the culture of research recruitment for the better.”
“There’s not an easy fix here,” said Jeffrey Botkin, MD, MPH, Professor of Pediatrics at the University of Utah, where he is also Adjunct Professor of Human Genetics, Chief of the Division of Medical Ethics and Humanities, and Associate Vice President for Research Integrity. Botkin, Chair of the U.S. Department of Health and Human Services (DHHS) Secretary’s Advisory Committee on Human Research Protections (SACHRP), said he believes new regulations or guidance from DHHS are necessary to improve informed consent and make participant forms less daunting and more understandable: “We’re trying to give IRBs a little more flexibility in consent forms. My hope is to encourage a SACHRP formal initiative in this domain. IRBs take guidance very seriously… I don’t think anyone is going to change on their own unless there’s broad systemic change.”
Deborah Collyar, founder of Patient Advocates in Research, agreed: “We’ve been talking about these issues since I got involved in research 20 years ago. “Now it’s time for action.”