| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
You are here > Biopharmaceutical Glossary Homepage/Search > Drug discovery & development: Clinical trials Clinical
trials glossary & taxonomy
Applications Map Informatics map Technologies
map Biology map
Finding guide to terms in these glossaries Site
Map Ethics adaptive
clinical trials:
A process for improving the efficiency of clinical
trials based on interim analyses of clinical data, potentially leading to
reductions in overall sample size, shorter project duration, improved quality of
results, and reduced costs. Tufts Center for the Study of Drug Development,
Glossary of terms, 2007 http://csdd.tufts.edu/InfoServices/Glossary.asp The pharma industry is
gradually coming to realize that the classically structured clinical trial does
not offer enough flexibility to make use of continuously emerging knowledge that
is generated as the trial progresses. Unacceptable levels of attrition in the
clinical stage of development are driving profound changes in the architecture,
design, and analysis of clinical trials. The majority of respondents to our
survey said that reduction in patient numbers, less exposure to study drug, and
drops in overall trial duration were key points in favor of adaptive designs;
however, a majority also had specific concerns with adaptive
trials―concerns that involved methodological, logistical, and regulatory
uncertainties: Herman Mucke, Adaptive
Clinical Trials: Innovations in clinical trial design, management and analysis, Insight Pharma Reports, 2007 Adaptive Clinical trials
webcast Jerald Schindler, VP Biostatistics and Research Decision Sciences Late
Stage Clinical Statistics, Merck Research Laboratories, 2007 http://www.bio-itworld.com/webcasts/lsw/schindler.aspx Tools such as toxicogenomic
assays can provide important information about a drug's effectiveness and
safety. An adaptive trial would generate and incorporate such information to
help guide the more effective use of medicines. In an adaptive trial, for
example, patient outcomes could be used as they became available to adjust the
allocation of future patients or some other aspect of the study design. Adaptive
Clinical Trials Are Steppingstone toward Personalized Medicine,
PharmaWeek, July 10, 2006 http://www.healthtech.com/news/strategic_briefings/2007/When%20Smaller%20is%20Better.asphttp://www.pharmaweek.com/Regulatory_And_Legal/Adaptive%20Clinical.asp See
related pivotal clinical trials. attrition: Unacceptable levels of attrition in the clinical
stage of development are driving profound changes in the architecture, design,
and analysis of clinical trials. The majority of respondents to our survey said
that reduction in patient numbers, less exposure to study drug, and drops in
overall trial duration were key points in favor of adaptive designs; however, a
majority also had specific concerns with adaptive trials―concerns that
involved methodological, logistical, and regulatory uncertainties: Herman Mucke,
Adaptive
Clinical Trials: Innovations in clinical trial design, management and analysis, Insight Pharma Reports, 2007 Bayesian
clinical trials: In recent years, there has been an explosion in
predictive technologies to help researchers select only the most promising
candidates for clinical development. The need for such tools is driven by the
disastrous economic consequences of late-stage failures, which account for over
60% of all drug terminations. Insight Pharma Reports, Bayesian
Forecasting of Phase III Outcomes: The Next Wave in Predictive Tools, 2007
CDISC
Clinical Data Interchange Standards Consortium: An
open, multidisciplinary, non- profit organization committed to the development
of industry standards to support the electronic acquisition, exchange,
submission and archiving of clinical trials data and metadata for medical and
biopharmaceutical product development. http://www.cdisc.org/
Clinical Data Interchange
Standards Consortium: http://www.cdisc.org/ clinical development: The phase of drug development in which
investigational new drugs (INDs) are tested on humans under the control of
clinicians. Clinical development is necessary to obtain approval to market new
drugs. http://www.biotechshares.com/glossary.htm clinical
forecasting: It is clear that late-stage clinical failures
account for a large proportion of the expenses. This can be as a result of both
the large out-of-pocket investments in Phase III clinical trials and because
unsuccessful trials tie up capital resources during their conduct, and
potentially also for the time spent during any attempted recovery following
regulatory rejection. So, there is an interest in strategies that could halt, as
early as possible, the development of drugs that eventually fail. Clinical
forecasting in drug development, Asher D. Schachter and Marco F. Ramoni,
Nature Reviews Drug Discovery 6, 107-108 (February 2007) |
doi:10.1038/nrd2246 http://www.nature.com/nrd/journal/v6/n2/full/nrd2246.html Narrower term: Bayesian
clinical forecasting, Bayesian clinical trials clinical genomics -
clinical trials impact: Clinical genomics is the
application of large-scale, high-throughput genomics technologies in clinical
settings, such as clinical trials or primary care of patients. Clinical genomics
promises to allow a molecular understanding of disease and drug response, with
benefits in all areas of medicine. Contributing to the growth of genomics, in
2005 the FDA issued guidelines for applications of genomics in drug development,
with the stated hope that genomics will improve the safety and effectiveness of
medicines. Given this mandate, clinical genomics applications appear to have
crossed a threshold with the recent approval of several clinical genomics
products. Insight Pharma Reports, Impact of Genomics on Clinical Trials,
2006 http://www.insightpharmareports.com/reports/2006/61_Clinical_Genomics/overview.asp
clinical informatics: Integration of clinical workflow and business
strategies of any healthcare organization will spell success for the providers
of the future. Efficient exchange of data and information is essential for this
merger, and information technology is the tool with which to accomplish the
consolidation. Clinical Informatics is the practice evolving from this need in
healthcare. HIMSS Clinical informatics http://www.himss.org/ASP/topics_clinicalInformatics.asp The American Medical Informatics Association (AMIA) will attempt to elevate applied clinical
informatics to the level of medical subspecialty with the help of a $300,000
grant from the Robert
Wood Johnson Foundation (RWJF). .... AMIA sees
applied clinical informatics as not being essentially different for doctors as
it is for pharmacy or nursing or any other health profession,” Detmer says.
AMIA to Develop Clinical Informatics as Certifiable Specialty, Neil Versel,
Digital Healthcare and Productivity, May 2007 http://www.health-itworld.com/newsitems/hitw/amia-clinical-informatics The
application of informatics approaches to the clinical- evaluation phase of drug
development. These approaches can include clinical- trial simulations to improve
trial design and patient selection, as well as electronic capturing and storing
of clinical data and protocols. The goal is to reduce expenses and time to
market. Clinical Project Management October
6-7, 2010 • Philadelphia, PA Program
| Register | Download Brochure clinical trial data model: Phase Forward Submits XML-based Clinical Trial Data
Model to Worldwide Standards Organizations, 1999 http://www.oasis-open.org/cover/phaseCDISC19990621.html clinical trial simulation: A relatively new effort to devise in silico
simulations of human physiology and genetic variation to help identify which
compounds will eventually fail in the drug development process. Related
term: Genetic
manipulation & disruption
systems biology clinical trials: The current clinical evaluation process is fraught
with inefficiencies, resulting in numerous compound failures and exploding
development costs. Until recently, the industry has reacted to the clinical
evaluation problem essentially by "streamlining" the existing
processes and by introducing information technology in a cautious and
evolutionary fashion. While the FDA’s Critical Path Initiative of 2004 showed
that the agency is willing to take the lead in working with representatives from
industry and academia towards a remedy, this report suggests that a more radical
solution is needed. Insight Pharma Reports, Clinical Trial in 2015: A new
paradigm for clinical development, 2006 http://www.insightpharmareports.com/reports/2005/59_Clinical_Trials/overview.asp
The NIH
defines a clinical trial as a prospective biomedical or behavioral research
study of human subjects that is designed to answer specific questions about
biomedical or behavioral interventions (drugs, treatments, devices, or new ways
of using known drugs, treatments, or devices). Clinical trials are used to
determine whether new biomedical or behavioral interventions are safe,
efficacious, and effective. Behavioral human subjects research involving an
intervention to modify behavior (diet, physical activity, cognitive therapy,
etc.) fits this definition of a clinical trial. Human subjects research to
develop or evaluate clinical laboratory tests (e.g. imaging or molecular
diagnostic tests) might be considered to be a clinical trial if the test will be
used for medical decision making for the subject or the test itself imposes more
than minimal risk for subjects. Biomedical clinical trials of experimental drug,
treatment, device or behavioral intervention may proceed through four phases: See
also Phase I, Phase II, Phase III, Phase IV, Phase
Zero CenterWatch http://www.centerwatch.com/
A listing of more than 41,000 industry- and government- sponsored clinical
trials as well as new drug therapies recently approved by the FDA. Related
terms: CRO Clinical Research Organization, clinical informatics, comparative
data mining, FDA drug approvals, Phase I, Phase II, Phase III, Phase IV/
postmarketing surveillance, preclinical, predictive data mining Clinical Trial Design Task Force: The Clinical Trial Design Task Force (CTD-TF) of the National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations about aspects of phase II trial design that are the subject of frequent debate, such as endpoints (response versus progression-free survival), randomization (single-arm designs versus randomization), inclusion of biomarkers, biomarker-based patient enrichment strategies, and statistical design (e.g., two-stage designs versus multiple-group adaptive designs). Although these recommendations in general encourage the use of progression-free survival as the primary endpoint, randomization, inclusion of biomarkers, and incorporation of newer designs, we acknowledge that objective response as an endpoint and single-arm designs remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on characteristic specific to the situation. The Design of Phase II Clinical Trials Testing Cancer Therapeutics: Consensus Recommendations from the Clinica l Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee. Seymour L, et. al, Clin Cancer Res. 2010 Mar 9. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/20215557 clinical trials Asia: The globalization of R&D into emerging regions,
especially India, China and Southeast Asia continues. Growing R&D spending
in these regions has been driven by many factors including the attractiveness of
commercial markets there, more favorable economics including lower relative
costs for greater speed, access to highly skilled professional labor and a large
pool of treatment-naive patients. Pharmaceutical and biotechnology companies are
seeing rapid growth in the volume of their clinical trial activity in India,
China and Southeast Asia. At the same time these regions present unique
challenges that must be anticipated and managed. Clinical Trials Asia Strategies for
Planning, Placing and Implementing Clinical Trials in India, China and Southeast
Asia, March 2008,
San Francisco CA Google = about 1,840,000
July 31, 2007 See also global drug
development: Business glossary clinical trials- ethics: Ethics glossary clinical trials - Europe: A vast new opportunity for clinical trials has
emerged in Europe as a result of the collapse of the Soviet Union and events
during the last decade of the 20th century. The result is the emergence of
dozens of sovereign countries and gone is the political dividing line between
East and West Europe. Now these countries join the countries of Western Europe
as well as the CIS to offer a spectrum of clinical trial options. Among these
are: Treatment-naďve populations, Ease of patient recruiting, Superb trial
administration, Lower costs, Applicable EMEA standards or equivalents. Insight
Pharma Reports, Conducting
Clinical Trials in Europe: An insider's analysis,
2008 clinical trials - imaging: Molecular
imaging glossary comparative data mining: Algorithms &
data management glossary
Useful for clinical trial meta-analyses CONSORT Consolidated Standards of Reporting Trials, http://www.consort-statement.org/ CRO: An organization that conducts all or some of the clinical research involved in the drug or product development process on behalf of pharmaceutical research companies. An overview of drug development, Barnett/Parexel, 2000 http://www.barnettinternational.com/EducationalServices_Publication.aspx?p=6464&id=97141 Contract Research Organization or Clinical Research
Organization. Clinical trials are increasingly being run by outsourcing
to these groups. developmental site
agreements: Companies work with hospitals to develop
instrumentation and clinical research applications. drug development Latin
America: drug discovery pipeline: Drug discovery
& development glossary drug safety: Drug safety & pharmacovigilance
explanatory trials: Explanatory trials generally measure efficacy—the
benefit a treatment produces under ideal conditions, often using
carefully defined subjects in a research clinic. Martin Roland, David J
Torgerson, Understanding controlled trials: What are pragmatic trials? BMJ 316:
285 24 January, 1998 http://www.bmj.com/cgi/content/full/316/7127/285 Compare pragmatic trials
Large Streamlined Studies
LSS: management trials: Management questions are less focused on a
treatment's biologic activity; instead, they concern a treatment's effect on
patient outcomes in common practice. Thus, a management trial compares
treatment policies or strategies that can be widely applied, enrolling patients
as diverse as those likely to use the strategy. Intrusion on the standard of
care is small, and clinicians have as much discretion over patient management
and study drug discontinuation or re-initiation as they would in common
practice. Endpoints are clinical and easily ascertained, e.g., mortality or
serious disease, and data collection is minimal. Primary analyses are intent-
to- treat, with other analyses performed sparingly. MAPS: A Proposal for More
Clinically Relevant Research in AIDS, Carlton Hogan et. al, Univ. of Minnesota http://www.biostat.umn.edu/~carlton/MAPS.html meta-analyses,
meta-analysis: Research
glossary patient: People with a specific disease or condition,
particularly those being treated by a health professional.
Compare subject patient recruitment: Patient recruitment and retention are critical to drug development programs. Patient recruitment, if not adequately planned for, can extend your development timeline by a number of years. Retention of patients throughout the life of a clinical trial is essential in order have complete data sets for your analysis and subsequent filings.
The same trial treatment
options available at the University of Maryland are available at four affiliated
community hospitals where university-employed clinical research associates
(CRAs) have been placed, says [Mohan] Suntha, [MD].. Over the past several
years, 25 percent of participants in radiation oncology trials – or roughly 50
patients a year – have enrolled in their own communities rather than at the
university’s main campus in downtown Baltimore. “We’ve integrated
telemedicine technology with our commitment to clinical trial access,” says
Suntha. Telemedicine links provide a means for university-based investigators to
communicate with patients while they’re in a study. They also allow CRAs to
seamlessly transmit data mined at community- based sites. Patient
Recruitment: A Growing Role for Telemedicine? Deborah Borfitz, eCliniqua, Oct 1,
2007 http://www.bio-itworld.com/archive/eclinica/index_10012007.htm Patient Reported Outcomes
Consortium: The Critical Path Institute
(C-Path), in cooperation with the U.S. Food and Drug Administration (FDA) and
the medical products industry, has formed the Patient-Reported Outcomes
Consortium for the purpose of developing, evaluating, and qualifying PRO
instruments with the FDA for use in clinical trials designed to evaluate the
safety and effectiveness of medical products. http://www.c-path.org/PRO.cfm Phase
I: The main aim of this phase is to determine drug
safety. At this stage, drugs are tested in a small group of healthy volunteers
to determine the drug’s activity. Phase II: These trials are aimed at identifying the optimal
dose to be used in Phase III trials and, ideally, they identify drugs that will
not make it through the next phase of testing. Typically, Phase II trials are
double-blinded and have placebo controls. phase II clinical trials design: The optimal design of phase II studies continues to be the subject of vigorous debate, especially studies of newer molecularly targeted agents. The observations that many new therapeutics "fail" in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials, further emphasize the critical importance of robust and efficient phase II design. The Design of Phase II Clinical Trials Testing Cancer Therapeutics: Consensus Recommendations from the Clinica l Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee. Seymour L, et. al, Clin Cancer Res. 2010 Mar 9. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/20215557 phase II risk reduction:
See Chemistry glossary backup compounds Phase III: These studies, which take several years, can
involve thousands of patients at multiple trial centers. They are aimed at
definitively determining the drug’s effectiveness and its side- effect
profiles. These studies are also typically double- blinded and placebo-
controlled. Phase
IIIb: Subjects entered on a phase III trial may want to
stay on the drug after the study is completed and closed and while the data is
being readied for presentation. A Phase IIIB study allows
"compassionate" use of the drug during this interim time. [Human
Subjects Manual, Medical Issues, 10.2 Drugs and Biologics, Stanford Univ., 2001
http://humansubjects.stanford.edu/manual/chapters/ch10_2b_med.html Phase IV/ postmarketing surveillance: At this stage, after a drug has been launched, pharmaceutical companies may conduct further studies of its performance, often examining long- term safety. See also Regulatory Affairs Phase Zero, also known as microdosing pivotal clinical trials: The intermediate-sized clinical trials supported
through this RFA are a pivotal decision point in the NCI chemoprevention drug
development program. The consensus view of a Working Group from the NCI and the
FDA acknowledges that "the interim analysis of a validated surrogate
endpoint of cancer incidence may facilitate the timely and cost-effective
marketing of efficacious drugs (Kelloff et al., Cancer Epidemiol. Biomark. Prev.
4: 1-10, 1995)." Thus, the efficacy and safety data from these studies
potentially supports FDA marketing approval (NDA applications) for
chemoprevention indications, and certainly facilitates decisions regarding the
most appropriate recommendations for subsequent large, community-based efficacy
studies. Pivotal clinical trials for chemoprevention clinical development
National Cancer Institute, NIH RFA: CA-98-001 1997 http://grants.nih.gov/grants/guide/rfa-files/rfa-ca-98-001.html Related
term: adaptive clinical trials placebo non- responders: Non- responders on placebo] define a group that
would never improve their condition unless given the drug. They may be a group
that, if we could identify them, could be used to reduce clinical trial size.
Using this group in a proof- of -concept, it may be possible to test a drug even
without a comparative placebo and determine whether it is likely to be active.
Related
terms: disease resistant individuals, lure of initial value, placebo responders placebo responders: Most people think of the placebo response as a true
response. But much of it is actually regression to the mean. Clinical
trial subjects with more extreme symptoms are often selected because it is
desirable to see a dramatic effect upon treatment with the drug. Related terms: disease resistant individuals, lure of initial value, placebo non- responders pragmatic trials: Pragmatic trials measure effectiveness—the benefit the treatment
produces in routine clinical practice Martin Roland, David J Torgerson,
Understanding controlled trials: What are pragmatic trials? BMJ 316: 285 24
January, 1998 http://www.bmj.com/cgi/content/full/316/7127/285 Compare explanatory trials randomized clinical trials
RCTs: A study in which the
participants are assigned by chance to separate groups that compare different
treatments; neither the researchers nor the participants can choose which group.
Using chance to assign people to groups means that the groups will be similar
and that the treatments they receive can be compared objectively. At the time of
the trial, it is not known which treatment is best. It is the patient's choice
to be in a randomized trial. National Cancer Institute Dictionary of
Cancer Terms http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=45858 randomized controlled clinical trials: Are the gold standard for determining the efficacy of therapeutic interventions. However, medical practice has not evolved around the concept of randomized trials, but around the idea of careful observations, (anecdotal) case studies and the evaluation of retrospective data. Interventions discovered by these means and taken forward into clinical practice became standard practice as they continued to be superior when compared with prior or alternative types of treatment. Back to the future: why randomized controlled trials cannot be the answer to pharmacogenomics and personalized medicine, Frueh FW. Pharmacogenomics. 2009 Jul;10(7):1077-81 http://www.ncbi.nlm.nih.gov/pubmed/19604080 registries: See under Large
Streamlined Studies risk ratio: The ratio of risk in the treated group (EER) to the
risk in the control group (CER). This is used in randomised trials and cohort
studies and is calculated as EER/CER. [Glossary of EBM [Evidence Based
Medicine] Terms, Centre for Evidence Based Medicine, Mt. Sinai Hospital, 2000] http://www.cebm.utoronto.ca/glossary/ Single Controlled Trial
SCT: Since 1998, the FDA has allowed drug developers to
use what is known as the single controlled trial (SCT) to support their drug
approval applications. The SCT provision allows applicants to prove the
effectiveness of new drugs by submitting data from only one controlled clinical
study instead of multiple studies. SMO Site Management
Organization: Why a SMO is not a CRO or is it? Stan Woollen, FDA
2001 http://www.fda.gov/oc/gcp/slideshows/smo2001/smo.ppt stratification- clinical
trials: The FDA has been cautious
in forwarding any policy on genotyping and clinical trial stratification,
while at the same time trying to engage the industry in discussions on the
subject. subject: People being studied as part of clinical trials or
other investigation, including those serving as controls. Compare
patient.
women's health -
statistical modeling: Molecular
Medicine glossary Bibliography Bibliography
|
Contact
| Privacy Statement |
Alphabetical
Glossary List | Tips & glossary
FAQs | Site Map
