Home Visits Improve Willingness to Participate in Alzheimer's Clinical Trials

A Variety of New Methods May Improve Drug Discovery and Clinical Studies in


Jun 10, 2007, 01:00 ET from Alzheimer's Association

    WASHINGTON, June 10 /PRNewswire-USNewswire/ -- Alzheimer's clinical
 trials that include home visits could result in shorter recruitment periods
 and increased patient retention rates, and may save considerable time and
 expense, according to research reported today at the 2nd Alzheimer's
 Association International Conference on Prevention of Dementia in
 Washington, DC.
     Clinical trials are essential to testing the safety and benefit of
 promising new treatments for Alzheimer's and other diseases. Slow
 recruitment and loss of participants during the trial slows the progress of
 developing new treatments. It also increases the costs of research.
     Clinical trials for Alzheimer's face special challenges. They recruit
 not just the person with the disease but also at least one other person
 close to them, commonly called a caregiver, who has to accompany them on
 study visits. The patients often have functional and behavioral problems
 that make it difficult to get them ready for a study visit. The caregivers
 often have their own health problems and job demands that present
 challenges to study participation. In some cases, caregivers face the added
 burden of making a decision regarding treatment that may expose their loved
 one to risk.
     "Other than lack of sufficient funding, recruiting and retaining
 clinical study volunteers is now the single greatest impediment to
 developing better treatment and prevention strategies for Alzheimer's,"
 said William Thies, PhD, vice president for Medical and Scientific
 Relations at the Alzheimer's Association. The Alzheimer's Association
 recently implemented a Clinical Studies Initiative to elevate awareness and
 support of Alzheimer's clinical research among physicians and the public.
     With the expected rapid escalation in the number of people with
 Alzheimer's in the near future, and the accompanying financial, societal
 and personal catastrophes, scientists in government, academia and industry
 are working to improve drug discovery and the clinical trials that are used
 to test drug therapies. This includes improving the earliest stage of drug
 discovery on the "front end" so that development is more efficient and the
 compounds are more likely to be effective, plus understanding better and
 improving the recruitment and retention of participants into Alzheimer's
 clinical studies.
     Home Visits Improve Willingness to Participate in Alzheimer's Clinical
     Jason Karlawish, PhD, associate professor of medicine and associate
 director of the PENN Memory Center, and his colleagues at the University of
 Pennsylvania recently completed a study addressing the challenges of
 recruiting and retaining study participants for Alzheimer's clinical
 trials. They tested whether redesigned clinical trials might improve
 caregivers' willingness to participate in Alzheimer's trials by analyzing
 the value of four possible alterations in the study.
     The researchers interviewed 108 caregivers of community dwelling
 persons with Alzheimer's who were followed at the PENN Memory Center. The
 caregivers were asked questions about their willingness to participate in
 hypothetical studies which differed according to four variables: location
 of study visits, method of transportation to study visits, chance of
 receiving a drug or placebo, and level of risk of the study drug.
 Participants were asked to rank their willingness to participate in each
 varying study on a seven-point scale.
     The scientists found that 17 percent of participants were willing to
 participate in a high risk Alzheimer's disease redesigned clinical trial
 with no amenities. When home visits were added, the willingness to
 participate increased to 27 percent. Low risk, home visits, and a higher
 chance of the active treatment increased the willingness to participate to
 60 percent. The additional willingness generated by reducing travel
 inconvenience offset negative study features, such as taking a high-risk
 drug. Home visits also made caregivers of sicker patients more willing to
 participate in studies.
     "Altering studies to include home visits could result in shorter
 recruitment periods and increased patient retention rates," Karlawish said.
 "The amount of time we save through these alterations could offset the
 added costs of the home visits, and, in fact, we may save considerable time
 and expense if the participants don't have to come in to the clinic so
     Improving Drug Discovery at the Earliest Stages
     Over the past three decades, a problem has emerged in new drug
 discovery and development in which an increasing investment in research by
 industry and government is not proportionally reflected in successful new
 therapies. As such, a potential crisis is emerging, especially for diseases
 such as Alzheimer's, which is projected to reach epidemic proportions in
 the near future.
     The United States Food and Drug Administration (FDA) and National
 Institutes of Health (NIH) have made requests that academia and industry
 address the emerging crisis across multiple diseases by exploring
 strategies to improve efficiency and innovation in the drug discovery and
 development process.
     D.M. Watterson, Ph.D., Co-Director of the Center for Drug Discovery and
 Chemical Biology, John G. Searle Endowed Chair in Molecular Biology and
 Biochemistry, and Professor of Molecular Pharmacology and Biological
 Chemistry in the Feinberg School of Medicine at Northwestern University in
 Chicago, and colleagues from the Center for Drug Discovery and Chemical
 Biology (CDDCB) in Chicago, IL, met with their colleagues in industry and
 at government agencies to identify how they could respond to the need for a
 more effective process. Together, they developed "smart chemistry"
 integrated with "smart biology" approaches to drug discovery that have a
 potential for making the process more efficient, facilitate innovation, and
 identify novel compounds that might alter disease progression.
     The "smart chemistry" approach uses the information found in chemical
 and pharmacological databases to identify common strengths of molecules,
 defined by their physical properties, that turn out to be good drugs. The
 chemists mine these databases and propose testable hypotheses about what
 common themes among the physical properties of small molecules with
 different structures make them more drug-like. The identification of common
 themes aids in the design of new molecules.
     "The 'smart chemistry' approach to discovery allows a better fit
 between biology and chemistry at both the virtual molecule design phase and
 in the assembly line phase of synthetic production and testing," Watterson
 said. "This makes possible a more rapid and less costly response to
 biomedical needs as well as the generation of new molecules that are
 candidate compounds for development into new drugs."
     According to Watterson, the emphasis is on synthesizing compounds that
 have a higher probability to be stable, non-toxic, and cause fewer adverse
 effects. Minozac, a compound designed and synthesized in the Watterson
 laboratory, is an example of a novel compound developed using the
 integration of "smart chemistry" with "smart biology." Minozac limits
 excessive production of brain proinflammatory cytokines, which are small
 proteins that can cause tissue injury, and improves neurologic outcomes in
 animal models of diseases such as Alzheimer's, traumatic brain injury (TBI)
 and epilepsy. Minozac has been licensed to industry for clinical
     Collaborative studies with Linda Van Eldik, PhD, co-director of CDDCB
 and a Professor of Cell and Molecular Biology at the Feinberg School of
 Medicine, are exploring animal models of Alzheimer's and other brain
 disorders that have brain inflammation as a key contributor to disease
 progression. The ultimate goal is to develop a series of novel molecules
 which would be effective against a variety of disorders where brain
 inflammation and proinflammatory cytokine overproduction are involved.
     Patients With Greater Comprehension of Their Situation Are Willing To
 Accept More Risk
     As clinical trials move forward with promising new treatments for
 Alzheimer's, stakeholder perspectives can inform decisions about what risks
 are acceptable for what kinds of treatment benefits. Pharmaceutical
 companies, clinicians and the FDA need to understand patients' and family
 members' willingness to accept risky treatments for Alzheimer's. This
 information will provide important guidance on what drugs are appropriate
 for Alzheimer's treatment.
     "Several of the potential treatments being tested may present more than
 minimal risks to patients," Karlawish said. "For example, researchers had
 to stop one of the early studies of the anti-amyloid vaccination because
 subjects developed encephalitis, a dangerous inflammation of the brain."
     Karlawish and colleagues studied the willingness of persons with
 Alzheimer's to take risk to treat their disease. The study involved
 interviews with 34 community dwelling persons with very mild to moderate
 Alzheimer's who were followed at the PENN Memory Center and their
 caregivers. Patients were asked whether they would want to take medications
 which would delay the progression of Alzheimer's by one year, under varying
 levels of risk. The risks discussed were similar to those for drugs
 currently being researched for the treatment of the disease, and ranged
 from a 30 percent chance of pain to a 10 percent chance of death.
 Caregivers were asked similar questions on behalf of their relative.
     The researchers found that patients with more insight into the
 symptoms, diagnosis, and prognosis of their cognitive impairment were
 generally more risk tolerant. Risk-takers were also more likely to be
 judged competent to make a treatment decision and more capable of thinking
 through risks, benefits and purpose of an Alzheimer's medicine.
     "From the patient perspective, the willingness to take a risky
 Alzheimer's treatment is more driven by their awareness of their illness
 and their capacity to understand, appreciate, and reason through a
 treatment's purpose, benefits and risks to themselves, and not so much on
 the severity of their Alzheimer's disease," Karlawish said.
     Older Adults More Familiar With Alzheimer's Are More Willing To Accept
 Treatment Risks
     While the tremendous burden of Alzheimer's on people with the disease,
 families and society is acknowledged, there is little quantitative evidence
 of the level of risk individuals are willing to accept for treatment
 benefits. At the Alzheimer's Association Prevention Conference, Reed
 Johnson, PhD, Senior Fellow and Principal Economist at RTI Health
 Solutions, and colleagues reported results from a study on how much risk
 American older adults are willing to take in exchange for a disease
 modifying treatment for Alzheimer's.
     For the study, a nationally representative panel of 2,146 U.S. adults
 60 years of age and older (avg. 70 years) completed an Internet-based
 questionnaire. Respondents chose between pairs of hypothetical treatment
 alternatives, including different, 7-year, Alzheimer's-progression profiles
 and first year risk of death/permanent severe disability due to stroke or
 encephalopathy. The maximum acceptable risk (MAR) respondents were willing
 to accept in exchange for treatment benefits was calculated for various
 clinical benefit levels. Results were stratified based on respondent
 characteristics and familiarity with Alzheimer's.
     The scientists found that respondents were willing to accept a 46.8
 percent increase in the chance of death or disability in exchange for the
 benefit of preventing Alzheimer's disease progression beyond the mild
 state. Individual characteristics that had statistically higher MARs were
     versus older respondents, more educated versus less educated, and
 respondents familiar with Alzheimer's versus less familiar.
     "We found that older Americans are so concerned about the serious
 consequences of Alzheimer's that they are willing to trade a higher risk of
 other disabling illness or death in order to have access to a treatment
 that could delay the progressive and lethal consequences of Alzheimer's,"
 Johnson said. "This survey is the first to our knowledge that is able to
 quantify this fear of Alzheimer's in a manner that could be useful to
 health authorities as they plan for the increase in Alzheimer's brought on
 by the aging of our population."
     About the Alzheimer's Association Prevention Conference
     The Alzheimer's Association International Conference on Prevention of
 Dementia is the world's only multidisciplinary forum to convene
 professionals from the fields of bench research, drug discovery, medicine,
 care and public policy. More than 1,000 dementia experts from around the
 world will gather to present and discuss the latest detection, treatment
 and prevention research, and address how together we can prevent
 Alzheimer's from becoming a global health crisis. The 2007 Alzheimer's
 Association Prevention Conference will be held June 9-12 at the Marriott
 Wardman Park Hotel in Washington, DC.
     About the Alzheimer's Association
     The Alzheimer's Association is the leading voluntary health
 organization in Alzheimer's research, care and support. Our mission is to
 eliminate Alzheimer's disease through the advancement of research, provide
 and enhance care and support for all affected, and reduce the risk of
 dementia through the promotion of brain health. Our vision is a world
 without Alzheimer's. For more information, visit http://www.alz.org.
     -- Jason Karlawish -- Home Visits May Improve Recruitment In AD
 Clinical Trials. (Funders: Marion S. Ware Alzheimer Program)
     -- D. M. Watterson -- Improving The CNS Drug Discovery Process: Case
 Study With An Integrative Approach Yielding Novel Potential Disease
 Modifying Therapies. (Funders: National Institutes of Health, Alzheimer's
 Drug Discovery Foundation)
     -- Jason Karlawish -- How Much Risk Is An Alzheimer's Disease Patient
 Willing To Take To Treat Their Alzheimer's Disease? (Funders: Marion S.
 Ware Alzheimer Program, Paul Beeson Faculty Scholars Award)
     -- F. Reed Johnson -- The Effect of Individual Characterictics on
 Benefit- Risk Trade-Offs for Modifying the Progression of Alzheimer's
 Disease. (Funder: Elan Pharmaceuticals, RTI International Senior

SOURCE Alzheimer's Association