january 2017 a centerwatch publication volume 24, issue 01 … · 2017. 1. 3. · acquisitions,...
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Collecting genetic and biomarker data adding to site administrative burdenBy Karyn Korieth
As the analysis of genetic data is fast be-coming a significant part of clinical research programs, both to enroll study
participants and understand how drugs work, investigative sites are increasingly asked to collect genetic samples and conduct genetic screenings for clinical trials.
Research sponsors want investigators to col-lect genetic material that either can be analyzed as part of the study or stored for future test-ing. Depending on the relevance of the genetic analysis to the clinical development program, the genetic sample collection may be a core requirement for study participation or an op-tional component of the study.
“We are seeing more industry-funded re-search that wants to do genetic testing to make sure that they are on the right pathway in their drug development and in targeting
populations,” said Megan Bailey, manager of the Office of Research Compliance, CHOC Children’s Research Institute at the California-based Children’s Hospital of Orange County (CHOC). “We’ve also seen an uptick in the number of protocols that look at genetic test-ing along with tissue banking because of not knowing what tests may come in the future and wanting to prepare for those.”
While the increasing use of genetic bio-marker data can enhance medical knowledge, lead to more efficient drug development and
ultimately deliver more beneficial therapies, the approach also has implications for the ef-ficiency of the study conduct process.
Interviews with investigators and site staff members suggest that the informed consent process takes longer for studies that include a genetic component, for example, since inves-tigators need to ensure study participants un-derstand what will happen with their genetic information and answer questions about how the data will be protected. Some sponsors re-
Personalized medicine impacting study conduct
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Online patient recruitment: Still nascent after all these years
January 2017 A CenterWatch Publication Volume 24, Issue 01
see Patient recruitment on page 12
Industry is ready for a revolution,but kinks still existBy Suz Redfearn
T he world of online patient recruit-ment has undergone an evolution since it arrived during the heady
dot-com craze of the 1990s—but has that caused a revolution, one that has trans-formed the space?
Most say no, not yet. But it may be on its way to doing so.
It all began when the internet surged in the late 1990s: a slew of companies—largely private equity and venture-backed—formed to leverage the reach of the Internet to im-prove patient recruitment effectiveness.
During the dot-com craze, market entry and access to capital were easy, and numer-ous companies entered, including Acurian, America’s Doctor, Clinicure.com, Drkoop.com, EmergingMed and Veritas Medicine to name
but a few. Many of these companies did not survive when the dot-com bubble burst. Others had to modify their business models dramati-cally in order to survive and to remain viable.
Awareness and enrollment
What happened? What went wrong?For one, the early business model for
online recruiting companies didn’t work, explained Ken Getz, director of sponsored
see Personalized medicine on page 8
Changing pipeline composition
Source: Pharmaprojects; Evaluate Pharma
2015201020052000
29
21
45
20
11% 20% 29%
34%
Total new NDA/BLA approvalsPercent of total approvals for rare and specialty diseases
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An evolving regulatory landscape requires a specialized IRB.
Combining clinical expertise and deep regulatory knowledge with an insider’s understanding of the challenges facing cancer research centers, so investigators and their IRBs can focus on furthering cutting-edge research.
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In this issue4-6 In Review
Regulatory Update
Month in Review
7 Action Items
Saving studies with reader and assessor training By Joseph Pierro
Eliminating the swivel chair clinical investigator By Henry Levy
15-18 Pipeline News
FDA Actions
Study Lead Opportunities
New Drugs in the Pipeline
19 The Pulse on Global Trials
Coming in FebruaryPhysician engagementThe convergence of healthcare and clinical research
EHR/EMRSite processes around source data collection
January2017
Dear Readers,Happy New Year!The past few years, we’ve seen the industry evolve and move in different directions with mergers,
acquisitions, partnerships, technology, standardization initiatives and much more. I personally believe that in 2017, the industry will continue to evolve in response to these and other changes. CenterWatch will be here to keep you up-to-date on the latest news and trends.
The year is shaping up to be an exciting one for CenterWatch. The program agenda is being developed for the 2nd Annual Clinical Trials Collaboration conference scheduled for April 3-4, 2017, at the Renaissance Boston Waterfront hotel. The day-and-a-half program focuses on strategic collaborations and partnerships implemented to further success in the clinical trials enterprise. Please save the date and register for this dynamic and engaging event by emailing [email protected].
CenterWatch and ACRP’s partnership, established in 2014, continues to grow. In addition to ACRP members obtaining access to our products and services to assist in their day-to-day business operations, CenterWatch will support ACRP with virtual career fairs through our vast distribution channels, offering industry professionals potential new career opportunities.
In this issue, the lead story analyzes how genetic data is quickly becoming a significant part of clinical research programs in terms of patient enrollment and how investigative sites are being asked to collect genetic samples and conduct genetic screenings. The article also delves into the potential implications around genetic data collection. The second feature revisits the online patient recruitment environment and its evolution since the 1990s—the surge of the Internet. The article profiles a variety of different companies and their models in reaching patients for clinical trial participation.
Special Announcements:1. Clinical Trials Data Library: The team is working diligently on the new version of the Clinical
Trials Data Library with a target launch date of February. Further details will be shared with our readers during the month.
2. Benchmark & Survey Reports: New reports filled with data and insights are now available, including: Technology Solutions; Site Financial & Operating Performance; Clinical Development KPIs; and Risk Assessment & Risk-based Management Practices. Visit http://store.centerwatch.com/c-53-benchmark-reports.aspx for further details.
3. Profile Pages: Use online exposure to generate business leads and showcase business expertise, products and services. Online marketing profiles are customizable to any business operation, including investigate sites, site networks, academic medical centers and niche service providers. Contact [email protected] to learn more.
4. Advertising Packages: Plan your 2017 advertising campaigns with CenterWatch. Contact [email protected] to develop an advertising package to meet your 2017 business needs, whether it’s building company brand awareness, promoting a new product/service, webinar or white paper, open job opportunities, job career fairs or other business initiatives.
As we forge ahead in 2017, CenterWatch is poised for an exciting year of providing news, insights, trends and data on the clinical trials industry, including the results of our bi-annual Global Investigative Site Relationship survey and collaborative partnerships.
Warm regards,
Joan A. ChambersChief Operating Officer
The CenterWatch MonthlyISSN 1556-3367
Editorial & Production Assoc. Stephanie HillIntegrated Marketing Mgr. Susan SaloméDrug Intelligence Tracy LawtonProduction Renee Breau
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Send address changes to: CenterWatch Customer Service10 Winthrop Square, Fifth Floor, Boston, MA 02110CenterWatch Main and Editorial Offices:Tel: (617) 948-5100 Fax: (617) 948-5101Email: [email protected] January 2017 | The CenterWatch Monthly 3
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FDA Publishes Several Draft Guidance Documents
The FDA published several draft guidance documents. Although the dates for submit-ting comments will have passed before this is-sue is distributed, interested parties should still consider submitting comments on these draft documents with the indicated Docket Number included in the comments.
ICH E17 General Principles for Planning and Design of Multi-Regional Clinical Trials
In the September 9, 2016, Federal Register, the FDA announced the availability of a draft guidance for the industry titled “E17 General Principles for Planning and Design of Multi-Regional Clinical Trials.” The draft guidance was prepared under the auspices of the Inter-national Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The draft guidance describes general principles for planning and designing multi-regional clinical trials (MRCT). MRCT conducted according to the guidance will in-vestigate treatment effects in overall popula-tions with multiple ethnic factors (intrinsic and extrinsic factors as described in the ICH guid-ance titled “E5 Ethnic Factors in the Accept-ability of Foreign Clinical Data”) and evalu-ate the consistency of treatment effects across populations. The draft guidance is intended to increase the acceptability of data from MRCT as the primary source of evidence supporting marketing approval in global regulatory sub-missions and to thereby facilitate more efficient drug development and earlier access to medi-cines. One of the goals of harmonization is to identify and then reduce differences in techni-cal requirements for drug development among regulatory agencies. The ICH was organized to provide an opportunity for harmonization ini-tiatives to be developed with input from both regulatory and industry representatives.
The draft guidance provides guidance on general principles for planning and designing MRCT. Drug development has been global-ized, and MRCT for regulatory submission have widely been conducted in the ICH regions and beyond. Regulatory agencies are currently facing some challenges in evaluating data from MRCT for drug approval, and the ICH is devel-oping this harmonized international guidance to promote the appropriate conduct of MRCT and to focus especially on scientific issues in planning and designing MRCT. This new guidance will complement the E5 guidance on MRCT and facilitate MRCT data acceptance by multiple regulatory agencies. Interested parties may submit electronic or written com-ments as instructed above. Identify comments with Docket No. FDA-2016-D-2567.
Software as a Medical Device: Clinical Evaluation
In the October 14, 2016, Federal Register, the FDA announced the availability of a draft guidance titled “Software as a Medical Device (SaMD): Clinical Evaluation.” The draft guid-ance was prepared under the auspices of the International Medical Device Regulators Fo-rum (IMDRF), formerly the Global Harmoni-zation Task Force. The draft guidance pertains to the conduct of clinical evaluation of SaMD and focuses on the general principles of clinical evaluation, which includes establishing the sci-entific validity, clinical performance and ana-lytical validity for a SaMD. The draft guidance is intended to provide globally harmonized principles of when and what type of clinical evaluation is appropriate based on the risk of the SaMD.
IMDRF seeks to advance international har-monization or convergence of medical device regulation. It was organized to provide an op-portunity for global harmonization initiatives to be developed with input from both regula-tory and industry representatives. In Septem-ber 2016, the IMDRF Management Committee
Regulatory UpdateInReview
4 The CenterWatch Monthly | January 2017
CenterWatch Publications and ServicesClinical Trials Data Library A valuable online resource providing access to comprehensive charts and tables on the life sciences and clinical research industry.
CWWeekly A digital newsletter that reports on breaking news in the clinical trials industry distributed every Monday morning. Annual subscriptions are $249.
CenterWatch News OnlineA free, virtual newsletter that covers news, developments, drug and professional updates of the clinical research enterprise as it unfolds.
Research PractitionerA bimonthly publication providing educational articles and practical insights and tools for study conduct professionals. Subscribers can earn up to 18 ANCC contact hours each year. Annual subscriptions start at $143.
JobWatchA Web-based service featuring clinical research jobs, career resources and a searchable résumé database.
Drugs in Clinical Trials DatabaseA searchable database of 4,800+ detailed profiles of new drugs in development. Custom drug intelligence reports covering a variety of medical conditions can be prepared.
Clinical Trials Listing Service™An international listing service of actively enrolling clinical trials to support sponsors, CROs and sites in their patient enrollment initiatives.
Profile Pages Online marketing profile of your company’s expertise and services within the clinical trials industry.
Market Research Analytics ServicesData-driven and analytic market research services offered to assist orga-nizations in gaining competitive insights into market trends and their business.
Training Guides/SOPs/Reports l Benchmark Data Reports lCompilation Reportsl Protecting Study Volunteers in
Research, 4th Ed.l The CRA’s Guide to Monitoring
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Clinical Research l SOPs for Clinical Research Sitesl SOPs for Sponsors/ Medical Devices
ContactSales: (617) 948-5100, or [email protected]
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InReview
endorsed the draft guidance titled “Software as a Medical Device (SaMD): Clinical Evalu-ation” and agreed that the guidance should be made available for public comment. Com-ments about this draft will be considered by the FDA and the IMDRF SaMD WG. The FDA welcomes comments on all aspects of the draft guidance as well as eight particular issues of interest that are detailed in this notice. The draft guidance and the IMDRF comment page are available at http://www.imdrf.org/consulta-tions/consultations.asp#current. Identify com-ments with Docket No. FDA-2016-D-2483.
NIH Rule on Clinical Trials Registration and Results Information Submission
On September 21, 2016, the NIH of the feder-al Department of Health and Human Services (DHHS) issued this final rule (regulation/s). It details the requirements for submitting reg-istration and summary results information, including adverse event information, for speci-fied clinical trials to ClinicalTrials.gov, the clin-ical trial registry and results data bank oper-ated by the NIH’s National Library of Medicine (NLM). This rule provides for the expanded registry and results data bank specified in the FDA Amendments Act of 2007 (FDAAA) to help patients find trials for which they might be eligible, enhance the design of clinical trials and prevent duplication of unsuccessful or unsafe trials, improve the evidence base that informs clinical care, increase the efficiency of drug and device development processes, improve clinical research practice and build public trust in clini-cal research.
The requirements apply to the responsible party for certain clinical trials of drug products and medical device products that are regulated by the FDA and for pediatric post-market sur-veillance of a medical device product that is or-dered by the FDA. The final rule clarifies and expands requirements for the submission of clinical trial registration and results informa-tion to the ClinicalTrials.gov database. It imple-
January 2017 | The CenterWatch Monthly 5
Month in ReviewTop CWWeekly headlines from the past month:
l VA’s year in review shows firm ground gained for partnership expansions
l CRF Health expands in Romania
l IDEA Pharma, Mass Innovation Labs partner to reshape the development paradigm
l Evolving priorities in behavioral and social science research
l Parker Institute’s IRB Reliance Agreement signals a new phase in the trend toward consolidation
l Nonprofit, pharma, AMC partnership break ground on PSC research
l DrugDev acquires SecureConsent
l New specialty IRB targets social science research
Recent Pulse column topics:
l The Pulse on Patient Recruitment: Social listening or patient panels?
l The Pulse on Study Conduct: Experience and compromise make all the difference
l The Pulse on Site Success: Engaging the underrepresented patient population
l The Pulse on Global Trials: Movember—Bringing men’s health to the forefront
Executives interviewed for the Three Questions column:
l Irina Petrova, M.D., director of Clinical Operations, OCT
l Dr. Stella Blackburn, vice president and global head of risk management for real-world evidence solutions, QuintilesIMS
For more information about any of the above articles, please refer to Volume 20, Issues Issues 43-49. To subscribe to CWWeekly, visit http://store.centerwatch.com, or contact [email protected].
see Regulatory Update on page 6
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6 The CenterWatch Monthly | January 2017
InReview
ments provisions of the Public Health Service Act as amended by the FDAAA, which was in-tended to improve public access to information about certain clinical trials of FDA-regulated products. Those responsible for specified clini-cal trials of these FDA-regulated products have been required to submit registration informa-tion to ClinicalTrials.gov since December 26, 2007, summary results information for clinical trials of approved products as of September 27, 2008, and certain adverse events information since September 27, 2009.
This final rule does not impose require-ments on the design or conduct of clinical tri-als or on the data that must be collected dur-ing clinical trials. Instead it specifies how data that were collected and analyzed in accordance with a clinical trial’s protocol are submitted to
ClinicalTrials.gov. No patient-specific data are required to be submitted by this rule or by the law this rule is intended to implement. There were 901 comments received on the proposed rule after it was issued, which are presented as summaries in this notice. These regulations are effective on January 18, 2017.
NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information
On September 21, 2016, the NIH issued this policy to promote broad and responsible dis-semination of information from NIH-funded clinical trials through ClinicalTrials.gov. The policy establishes the expectation that all in-vestigators conducting clinical trials funded in whole or in part by the NIH will ensure that these trials are registered at ClinicalTrials.gov, and that trial results information is submitted
to ClinicalTrials.gov. The policy is complemen-tary to regulatory reporting requirements in 42 CFR 11.
This policy was first released as a draft on November 19, 2014. There were about 240 pub-lic comments on the draft policy from stake-holders such as researchers, academic/ research institutions, medical practitioners, patients, patient/disease advocacy groups, scientific/pro-fessional societies, device manufacturers, trade associations, not-for-profit non-governmental organizations, and the general public. Interest-ed readers are directed at the Overview of Pub-lic Comments (and a summary of responses from the NIH to those comments), provided in this notice. This policy will take effect January 18, 2017.
The Regulatory Update is excerpted from Research Practitioner, Volume 17, Number 6, November/December 2016.
Regulatory Updatecontinued from page 5
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January 2017 | The CenterWatch Monthly 7
There is a heavy burden on investi-gators and research nurses when
executing clinical trials and clinical care. In addition to the normal com-plexities of patient recruitment and care, investigative sites are stuck in the middle of multiple data entry systems. They move back and forth between electronic data capture (EDC) and electronic medical record (EMR) ap-plications to make sure information is recorded accurately and in the right place—a situation commonly known as “swivel chair interoperability.”
This process is unnecessarily com-plicated, leads to human error and ultimately puts trials and patient safety at risk. We’ve reached the point where technology can help eliminate
this burden. But which technology—the EMR or EDC application?
Potentially, it’s neither. We can make the leap to a seamless, electron-ic clinical research model with a tech-nology bridge that meets a physician’s needs for both trials and clinical care. Imagine a software application that is intelligent enough to know what data is needed for a trial versus a diagno-sis. Capture the data once, let the ap-plication figure out which system—the EMR or EDC—requires it, and simplify data entry for the physician.
We’re not far away. Common data standards are making healthcare and pharmaceutical systems work to-gether and a technology bridge pos-sible. Data will be easily shared and
useable between the many EDC and EMR systems that exist globally.
The potential benefits could be far reaching. Human data entry errors would be reduced. No more captur-ing information on Post-it Notes. And data would ultimately be in all the right places, without an added burden on clinical researchers and caregivers.
Now’s the time to move to an investigator-friendly approach. Re-move the incremental complexity of data entry and keep physicians fo-cused on taking care of patients and executing clinical research in a safe and effective manner.
Let’s eliminate the swivel chair in-vestigator. If the technology bridge is there, why wouldn’t we?
A lthough many CROs offer out-standing research capabilities,
not every assessor or overreader receives sufficient instruction to reduce variability and error. To avoid multimillion-dollar misfor-tunes, sponsors should prioritize assessor and overreader education to improve data quality.
1. Site evaluators or assessors must receive protocol training to reduce variability amongst data collection personnel. This should highlight: study endpoints, enrollment criteria and demo-graphic requirements; patient preparation to be completed before acquiring data points; equipment operation procedures for consistent data collection
and entry; the laboratory’s data acquisition standards, including patient-specific lead placement at each time point and expla-nations of protocol-required imaging sequences; and query resolution processes.
2. Overreading physicians must receive training prior to subject assessment to minimize inter- and intra-reader variability. Training should include: re-views of protocol design, pri-mary and secondary endpoints, time points and assessment criteria; an intracalibration session reviewing reading techniques, discussing scor-ing definitions and practicing reading case examples using
central laboratory systems; an intercalibration session com-paring findings to one another and to diagnostic standards; individual review sessions to certify performance before reading study cases; periodic reviews to test for variability and recalibrate; and adjudica-tion procedures—some studies use multiple overreaders with an adjudicator.
Well-trained readers and as-sessors are essential to reducing clinical trials’ data variability. With the ever-increasing costs, complexity and number of clinical trials, sponsors must rigorously train CRO personnel to maximize drug approval chances.
Henry Levy, chief strategy officer at Veeva, has nearly 25 years of experience transforming the way the biopharmaceutical industry improves patient health. He leads Veeva Systems’ market strategy and strategic relationships with customers and partners in multiple areas, including clinical. Levy also represents Veeva in various industry collaborations. Previously, he ran client development and commercial services at PPD, one of the world’s largest CROs, and was head of Accenture’s global life sciences R&D practice.
Saving studies with reader and assessor trainingBy Joseph Pierro
Eliminating the swivel chair clinical investigatorBy Henry Levy
Joseph Pierro is chief medical officer of Biomedical Systems, a premier global provider of centralized diagnostic services. He has served in global senior-level positions within the pharmaceutical industry and as a medical reviewer at the FDA Center for Drug Evaluation and Research. His thorough understanding of regulatory submission requirements and outstanding track record of success with regulatory approvals and responses to regulatory authorities make him an asset to Biomedical Systems’ Scientific Affairs team.
ActionItemsJoin the community of Action Item writers today! Email [email protected].
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8 The CenterWatch Monthly | January 2017
quire a separate consent form for the genetic component of the study. For clinical trials that target enrollment of patients with rare genetic biomarkers, sites may also be required to screen a larger number of patients to find qualified study participants.
When genetic information isn’t needed to make enrollment decisions for a clinical trial, there can be questions about whether the ge-netic analysis adds unnecessary procedures for investigative sites and contributes to the grow-ing complexity of clinical trial protocols. Yet investigators interviewed by CenterWatch view genetic screening and the collection of genetic materials not as a burden, but as an essential part of clinical research going forward.
“Any time there is anything extra in a clini-cal trial, it takes more time,” said Ryan Wel-ter, M.D., Ph.D., CEO and medical director of Massachusetts-based Regeneris Medical, which specializes in biological studies and re-generative medicine research. “But I wouldn’t necessarily call it a burden. Genetic infor-mation is incredibly important in terms of screening and understanding disease process-es. It is invaluable in making clinical, research and biologic decisions.”
Increase in protocols that request genetic material
Recent R&D trends show the use of bio-marker and genetic data accelerating in the development of drugs for many disease areas.
Analysis from the Personalized Medicine Coalition (PMC) showed that 28% of novel new drugs approved at the FDA in 2015 were clas-sified as personalized medicines, an increase from 21% in 2014. The Tufts Center for the Study of Drug Development (CSDD) found in 2015 that 42% of all drugs in development relied on biomarker data. In addition, a recent study published in Nature Genetics estimated the proportion of drugs developed with direct genetic support increased significantly across
the drug development pipeline, from 2% at the preclinical stage to 8% among approved drugs, and that selecting genetically supported targets could double the success rate for drugs in clini-cal development.
Sponsor companies use genetic biomarkers to evaluate patient response, which allows them to terminate ineffective drug candidates earlier in the development process, and to optimize clinical trial designs and outcomes by identify-ing which patient populations are most likely to respond to a drug therapy. Researchers also use genetic data to understand the mechanisms of both treatment response and disease process, which can help identify future targets for drug development.
“We are moving to an era where we use molecular analysis of patient samples either to
enroll people in trials or understand how drugs work or don’t work,” said Ross Levine, M.D., a physician-scientist at the Memorial Sloan Ket-tering Cancer Center in New York. “Molecular profiling, whether it’s based on the ideas of pre-cision-medicine initiatives or other ideas that have come out of our national research efforts, is the future and is becoming a part of routine care.”
Investigative sites interviewed for this story report that at least half of their active clinical trials request collection of genetic material, al-though it’s not a requirement for participation in all studies.
The genetic information is typically collect-ed from samples taken for other non-genetic study procedures. In some cases, there may be an extra tube of blood drawn during a screen-
IndustryNews
Personalized medicine continued from page 1
Personalized Medicine Coalition’s list of 13 personalized medicines approved in 2015
Drug name Disease condition Decision to treat affected by:
1. Alecensa (alectinib) non-small cell lung cancer
ALK biomarker
2. Tagrisso (osimertinib) non-small cell lung cancer
EGFR biomarker
3. Cotellic (cobimetinib) advanced melanoma BRAF biomarker
4. Nucala (mepolizumab) asthma eosinophil level
5. Aristada (aripiprazole lauroxil)
schizophrenia CYP2D6 biomarker
6. Lonsurf (trifluridine and tipiracil)
advanced colorectal cancer
VEGF, RAS and EGFR bio-marker
7. Repatha (evolocumab) high cholesterol familial hypercholesterolemia
8. Daklinza (daclatasvir) chronic hepatitis C infection
genotype 3 biomarker
9. Praluent (alirocumab) high cholesterol familial hypercholesterolemia
10. Rexulti (brexpiprazole) schizophrenia CYP2D6 biomarker
11. Orkambi (lumacaftor and ivacaftor)
cystic fibrosis F508del/CFTR biomarker
12. Cholbam (cholic acid) bile acid synthesis disorders
various single enzyme defect biomarkers
13. Ibrance (palbociclib) advanced breast cancer
ER and HER2 biomarker
Source: Personalized Medicine Coalition analysis, 2015 and 2014
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January 2017 | The CenterWatch Monthly 9
ing visit or an additional frozen tissue plate prepared during a biopsy, but investigators say these procedures generally don’t increase the workload for staff members.
“We are typically sent one lab kit and all of the collection tubes needed for the specific visit are contained in the kit. If there is a genetic marker that we are drawing for, it’s in the kit. There are no extra steps for us,” said Gabrielle Lewis, director of Clinical Research at Rege-neris Medical.
Most blood samples for genetic analysis can be sent to the lab for processing the same day and don’t prescribe specific handling require-ments. Yet some sponsors ask investigative sites to hold on to samples until they reach a certain volume before shipping if there are price benefits in batching the samples. In those cases, a freezer may be needed and the site must ensure the sample is still viable when shipped. Studies looking for specific enzyme levels associated with a disease state may also require that sites have capabilities to store and process genetic samples. In addition, study protocols increasingly require sites to provide and regularly maintain ultra-low temperature freezers, which have the capability to safely store DNA and other genetic material, as a prerequisite for study participation.
“We have to be savvy at the site on how to store samples properly and have the needed equipment,” said Lesia D. McBride, director of the Community Clinical Research Center (CCRC) at the Indiana-based Community Hospital of Anderson and Madison County. “We’ve always had the -70°C freezers, but now there is a discussion about -85°C freezers com-ing into play. Sites should make sure they have the right equipment for storage and that they have the right personnel trained to ship those samples so they are not destroyed or compro-mised during shipping. Sites are more chal-lenged because of the equipment we need to purchase and maintain. They are not cheap pieces of equipment.”
Although investigators report that study requirements for the collection of genetic ma-terial have had minimal impact on staff work-
loads so far, as sponsor demand for genetic data collection continues to grow, investigative sites may need to evaluate whether additional re-sources will be needed in the future.
“We see genetic data collection as very much an extension of our mission, vision and values at CHOC Children’s. We do not consider it a burden,” said Brent Dethlefs, executive direc-tor of CHOC Children’s Research Institute, which conducts both basic science and clinical research. The hospital’s Hyundai Cancer Ge-nomics Program also began a molecular pro-filing study in 2011 that has compiled genomic data from some 400 cancer patients. “But there is no doubt that this presents a resource chal-lenge. It’s important to pay attention to our infrastructure and look forward, as the field continues to progress, to ensure we are ahead of the curve. We don’t want to catch our chief executives by surprise when suddenly we need more space or more human resources to bring to bear on this.”
Additional time required for informed consent
When a clinical trial includes a genetic com-ponent, the investigator or site staff members typically need to spend more time with poten-tial participants during the informed consent process to answer questions and ensure study participants understand what will happen with their genetic information, the scope of any in-tended future research use and the intended duration of sample storage.
“There are time constraints on making sure
that we have explained everything to the sub-ject well enough,” said CCRC’s McBride.
Informed consent for the collection of genet-ic samples may be obtained either in the main informed consent form or a separate docu-ment, depending on the approach required by the research sponsor.
Investigative research sites at academic med-ical centers or hospitals that develop their own clinical trial protocols and informed consent forms have needed to revise their processes and documents to incorporate new national medi-cal society and industry recommendations about disclosing genetic results to participants and to ensure the consent process addresses ethical review board concerns. The Industry Pharmacogenomics Working Group (I-PWG), an informal association of 20 companies in-volved in pharmacogenomics research, for example, has developed guidelines that recom-mend consent for future use of samples should patients withdraw their consent and request destruction of their samples.
“Participants should be given control over their material, deciding for what it will be used and how broadly it will be distributed,” said Sharon Terry, president and CEO of the Genet-ic Alliance, a nonprofit health advocacy orga-nization that includes a network of more than 1,200 disease-specific advocacy groups. “There is usually pushback on this because research-ers are not using network-age technologies to recruit and stay engaged with people. Instead of recruitment and consent, this should be thought of as ongoing engagement.”
Development compound reliance on biomarker dataPercent of total compounds in R&D that are collecting biomarker data
Source: Tufts CSDD, 2015 <csdd.tufts.edu>
58%
42%
23%
Late clinical (phase IIb-IV)Early clinical (phase I-IIa)Preclinical
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Confidentiality and proper data protection are among the chief concerns expressed by po-tential participants. Some patients worry that individual genetic data could be used against them by an insurance company or employer. Investigators interviewed for this story, how-ever, stated that genetic data doesn’t inherently present greater privacy risks than any other data collected in a clinical trial.
“Your DNA is highly confidential and you want to preserve that information. But all healthcare data is incredibly confidential. Our informed consent process should be the same for all privileged healthcare information, no matter what. Our systems are already set up to safeguard this information, whether you are giving a sexual history, a psychological history or just a basic medication history. All protected health information pieces require the same amount of vigilance,” said Regeneris Medical’s Welter.
Site staff also must answer patient questions about whether they will have access to the re-sults of genetic tests and, when appropriate, provide genetic counseling for patients or have study participants follow up with a medical ge-neticist to discuss research findings.
“While some studies do share the results of the study-specific genetic tests with subjects, not all do. Also, some studies collect samples for future testing, which typically are not shared with the patient since any identifying infor-
mation about the patient is removed from the sample once it is sent to a genetic repository,” said Marshall L. Nash, M.D., a principal inves-tigator at the Georgia-based NeuroStudies.net, a clinical research site that focuses primarily on finding treatments for Alzheimer’s disease.
Investigators report that study participants generally don’t object to collection of their ge-netic material, even when it’s an optional com-ponent of a research study, once their questions about privacy protections have been answered. A study published earlier this year by the Royal Marsden NHS Foundation Trust in the U.K. found that 78% of cancer patients surveyed said they would donate their tissue for genetic research. Other studies published in medical journals also report generally favorable public attitudes about participation in genetic testing.
“We underestimate patients’ willingness and their incredible motivation to be part of something bigger than themselves,” said Sloan Kettering’s Levine. “Particularly in cancers where people feel their disease is rare and not studied enough, I am always impressed and humbled by patients’ excitement to be part of trials. When people come to Sloan Kettering, they don’t say, ‘I don’t want you to poke and prod the DNA of my tumor.’ They say, ‘Are you going to do everything you can to figure out what’s in it?’”
Increased patient recruitment challenges
When genetic studies are added to a clini-
cal research program as an optional sub-study for participants, investigators find they don’t affect patient recruitment since the efforts fo-cus on finding volunteers for the overall study, not the genetic component. Yet investigative sites often find it more difficult to recruit for clinical trials that target patients with a spe-cific genetic variant, and site staff might be required to screen a larger number of people to find study participants that could qualify. Some companies offer free genetic testing kits to help investigators identify potential study participants with the specific genetic bio-marker criteria required. Other sponsors pay for the additional screenings that are needed, but sometimes screening costs are shared be-tween sites, CROs and sponsors.
For rare disease protocols that require en-rollment of patients with specific genomic alterations, which are notoriously difficult to recruit given the small patient populations, investigators typically work with patient advo-cacy groups or use social media to advertise the research study and find the right participants.
“If you have a rare disease for which you have a genetic test, those patients usually find you. If you have a rare disease that may not have a genetic marker, they may still find you,” said Douglas Lee, M.D., a pulmonolo-gist who practices at Wilmington Health and serves as a principal investigator with PMG Research of Wilmington in North Carolina. “I have people fly from Ohio, South Carolina or Georgia to be in a study because there may only be a few places around that are involved in a research study.”
The use of electronic medical records and patient databases have also become increas-ingly important tools for recruiting patients for protocols with a genetic component. At the Research Institute of Deaconess Clinic in Evansville, Indiana, for example, researchers used a two-prong approach for identifying a subpopulation of myocardial infarction (MI) patients with a specific genetic biomarker, which the sponsor estimated that one-in-five MI patients would have. Staff first monitored the daily hospital census for patients with a
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10 The CenterWatch Monthly | January 2017
Methods sponsors are using to prove clinical utilityPercent of total
Source: Tufts CSDD, 2015; n=24 sponsor companies <csdd.tufts.edu>
71%
50%
25%
4%Nothing new at this time
Engage healthcare providers as consultants
Partner with payers
Conduct specially designed clinical trials
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recent MI event and identified potentially eligible patients before they were discharged. At the same time, electronic medical records were used to create a post-MI patient pool based on the inclusion/exclusion criteria of the protocol.
“Patients were contacted and phone-screened for eligibility and interest. Targeted patients were then scheduled for screening appointments and genetic testing was done at the screening visit to determine eligibility,” said Gregory A. Folz, administrative director of the Research Institute of Deaconess Clinic.
New partnerships emerging
New collaborations have be-gun to emerge that address the unique challenges associated with conducting clinical trials that include genetic screening and analysis. Consortiums are being developed around vari-ous rare disease types to fa-cilitate study enrollment and data sharing. Partnerships be-tween industry and research communities have also been formed to advance targeted therapies.
In one instance, the Leukemia & Lym-phoma Society (LLS) recently launched a precision-medicine clinical trial for acute myeloid leukemia (AML) patients with an unprecedented collaboration between re-searchers, academic medical centers, bio-pharmaceutical companies, the FDA and multiple support groups. While a typical clinical trial only studies one drug or one combination of drugs, the Beat AML Mas-ter Trial, which will be managed by INC Research, began with four different treat-ments that will each be tested in one of sev-eral arms of the trial based on a particular genetic mutation.
Newly diagnosed AML patients will have their genomic data analyzed within seven days and be assigned a specific treat-ment arm of the trial based on the screen-
ing results. Since the study involves genetic analysis in an acute disease and most AML patients are rushed into standard treatment immediately upon diagnosis, the trial de-sign needed to ensure that both the bone marrow biopsy and the screening analysis could be completed within a week.
“That created aspects that are unique to this trial,” said Levine, one of the lead in-vestigators who worked closely with LLS to plan and design the master protocol for the trial. “We are screening AML patients over 60 years old who have a relatively small number of standard criteria. But because we are breaking those AML patients into dif-ferent subsets, we wanted to have enough
patients for each subset to test the specific question. No single center can do that alone. We are hopeful that this will pave the way for other trials like this where we do genetic analysis and use that to decide about thera-peutic questions and test therapeutic ideas.”
Through the collaboration, participants hope to show that the various stakehold-ers have the desire to work together and the ability to get targeted treatments to newly diagnosed patients in a narrow time frame, which could open other opportunities mov-ing forward.
“When you look at an acute disease like acute myeloid leukemia and a newly diag-nosed patient walks in the door, you need a more or less instant decision to get going with an appropriate therapy,” said Nicholas Kenny, Ph.D., executive vice president and general manager for oncology at INC Re-
search. “That puts pressure on the logistics to get the NGS [next generation sequencing] testing across this panel done very quickly so we can make an informed decision about which therapy is appropriate for the patient. If this will work for Beat AML, it becomes precedent-setting for what is achievable in other tumor types.”
Looking ahead
The rapid move toward personalized medicine and an increase in clinical re-search programs that include genetic analysis has the potential to accelerate changes already under way in the global
investigative site market. The site landscape will continue to consolidate and clinical research will move increas-ingly toward larger hospitals, healthcare systems and site networks as sponsors and CROs want to place clinical trials in settings that have access to large patient popu-lations and electronic health records that can help iden-
tify specific subpopulations for genetic re-search.
“If you have a big network, you can find more of those rare diseases than you can if you are a small practice,” said PMG Re-search of Wilmington’s Lee. “If you are a small family doctor, you may have many pa-tients that meet the eligibility requirements, but you don’t know because you don’t have the ability to find them, whereas I have a bigger patient database and can find them by searching my electronic medical record.”
Yet INC Research’s Kenny said the clini-cal research enterprise must find ways to keep smaller sites involved in clinical trials that include genetic analysis. Approaches could include simplifying testing require-ments, for example, and reducing the administrative burden of conducting a
January 2017 | The CenterWatch Monthly 11
“Genetic information is incredibly important in terms of screening and
understanding disease processes. It is invaluable in making clinical, research
and biologic decisions.” —Ryan Welter, CEO and medical director, Regeneris Medical
see Personalized medicine on page 12
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clinical trial. In addition, a “portfolio ap-proach” that offered sites multiple study opportunities within a tumor type or mo-lecular-defined marker also could encour-age wider investigator participation.
“If we let precision medicine drive trials just into bigger centers, then we’ve failed. That helps nobody. The physicians are not getting the experience with the drug and the patients aren’t benefiting,” he said. “If we can’t get that right, then we have failed in our mission to broaden out what I would consider to be patient-centric trials.”
Karyn Korieth has been covering the clinical trials industry for CenterWatch since 2003. Her 30-year journalism career includes work in local news, the healthcare indus-try and national magazines. Karyn holds a Master of Science degree from the Columbia University Graduate School of Journalism. Email [email protected].
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12 The CenterWatch Monthly | January 2017
research programs at Tufts Center for the Study of Drug Development (CSDD), chairman of the Center for Information and Study on Clinical Research Participa-tion (CISCRP). Getz is also the founder of CenterWatch, which was, in the mid-1990s, the first website to publish active industry-funded clinical trials categorized by dis-ease for patients to identify opportunities to participate.
“The first generation Internet recruit-ment companies weren’t positioned prop-erly,” said Getz. “They only promoted clinical trials paying for patients and the payment model was predicated on an en-rolled patient—with no upfront fee re-quired,” he explained. “A lot of sponsor companies liked the low-risk approach, but the Internet companies could not deliver
sufficient enrollment performance to cover shareholder and investor requirements.”
That’s because looking for patients on the Internet—either by intercepting them in diseased-based communities or run-ning ads in the places they visit—resulted in “filling the top of the funnel with inter-ested parties, but then not many of them sifted down to the bottom of the funnel to actual recruitment,” said Hugo Ste-phenson, executive chairman of DrugDev, founder of iGuard, later named Medi-Guard, an online recruitment tool that was bought by Quintiles. Stephenson has now also returned to being a principal investi-gator in Australia.
“Years ago, the perception was that the true answer lay in simply getting the mes-sage to patients that trials were out there, and the belief was that most people would consider being in a clinical trial if they’d only heard of them,” said Stephenson. “The
Holy Grail was thought to be awareness, but that didn’t turn out to be the case.”
Instead, it was much more complicated than that. If a patient or their caregiver is highly motivated—envision a cancer pa-tient with no other options or the parent of an autistic child where there is unmet need—yes, they will move mountains to enter a trial once they learn about it. But the rest of the population? Not so much, said Stephenson. And even less so if the trial is inconvenient or not particularly pa-tient-friendly, which is even more common these days as trials have gotten more com-plicated. Also, the patients who are willing to be in a trial may not be the ones a study is actually looking for.
And the early online companies may have been good at aggregating useful in-formation on trials in one or two therapeu-tic areas and matching potential patients against inclusion/exclusion criteria, but were unable to come up with algorithms for doing that across all trials in all areas.
All of this, said Getz, squashed the early dream of easy online recruiting.
Better data crunching
The dream, however, is still alive; it just looks a bit different in an online world de-fined by social media and sophisticated as-sessment of individual behavior.
Enter Antidote. Launched in 2010 as Tri-alReach, Antidote is in the process of build-ing a meta search engine for clinical trials with a free side for patients and a pay side
Internet access by adults as a proportion of time spent online per dayPercent of total time
Source: KPCB
2009
3
77%
Computer Mobile device
2011
3.7
2013
4.9
2015
5.6
23%
70%
30%53%
47%
57%
43%
Total hours/day online
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for sponsors and CROs. The model is not new, but this time the company believes it has more firepower; Antidote’s co-founder and CEO is Pablo Graiver, previously VP of business development in Europe at the travel meta search engine Kayak. And this time, the effort has 83 people sitting in a room perpetually trying to restructure vo-luminous inclusion/exclusion criteria for every clinical trial out there in an effort to make it easily searchable.
“No one had before tackled the fundamen-tal problem at scale for all disease areas, and that’s important now as medicine is getting more refined,” said Sarah Kerruish, Antidote’s chief strategy and growth officer areas. “Re-structured protocols are matchable protocols.”
Antidote partners with health portals including Healthline, Everyday Health and CenterWatch, as well as patient networks like WEGO Health and CureClick and dis-ease groups communities like JDRF. Anti-dote also said it’s working with the World Health Organization, and “half of the top 20 pharmaceutical companies.”
Others—Clairiness, Inspire, Patients-LikeMe, Health Unlocked and Quintiles’ digital effort—are using a similar model with some success. Regardless, these com-panies have one central problem that will keep them from revolutionizing the field, said David Kronfeld, senior director of corporate development at Medidata Solu-tions.
“The fundamental flaw with online pa-tient recruiting is that it depends on pa-tients to explore treatment alternatives beyond the recommendations of their physicians,” he said. “True, patients are increasingly taking an active role in their care so it seems plausible to engage patients online where they seek information. How-ever, this is unlikely to scale.”
EHR a game changer?
Kronfeld and others who closely watch the space say the real future of web-en-
abled recruiting lies in the mining of elec-tronic health records (EHR).
Enter, EPatientFinder: This two-year-old, venture-backed Texas company’s model in-volves partnering with EHR companies to pinpoint patient data and enroll protocol-eligible patients. The concept involves “geo-precise heat maps” of specific regions show-ing exactly where the patients are, exactly who their doctor is and then “harnessing the power of the trusted physician-patient relationship in a consult setting.”
“There are tens of thousands of clinical trials running at any given moment—it’s impossible for a primary care physician to keep up with them,” said Tom Dorsett, founder, president and CEO of ePatient-
Finder. “We educate them on trial oppor-tunities, then help them identify specific patients. Patients say they like getting a call from their trusted physician who has sought out a trial opportunity for their chronic condition.”
Does it work? ePatientFinder claims it does. According to their numbers, of the patients contacted, 85% say they’re inter-ested in the trial, and of the referrals sent to trial sites, 78% are accepted into the trial.
Still, it’s very early days for this EMR-mining concept, which is a complicated one.
Dave Comen, chief strategy and mar-keting officer at ERT, formerly SVP head of
Worldwide internet penetration ratesPercentage of total population with internet access (estimated global population 2016: 7.2 billion)
Source: Internet World Statistics, 2016
North America
86%
54%
29%
62%
Europe LatinAmerica
MiddleEast
AsiaPacic
Africa
74%
48%
Profiles of select online recruiting companies
Inspire Health Unlocked
Antidote(formerly TrialReach)
ePatient Finder
Year founded 2005 2009 2010 2013
Capital raised N/A $6.7 million (est)
$17.9 million $11.4 million
Investors Tenfore Holdings
Individual investors
Amadeus Capital Partners; Octopus Ventures; Smedvig Capital
Parsons and Whittemore
Monthly patient traffic
1 million visitors
3.5 million visitors
N/A N/A
Source: CenterWatch, 2016 *based on company reports and interviews
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health engagement and communications, chief marketing and communications offi-cer at Quintiles (Digital), said, “EMR min-ing is very nascent at this point. There’s an accessibility issue; the data you get out isn’t necessarily the data that you’re requesting. And the other issue with this approach is competition: Does the physician really want to refer his or her patient away and into a trial? Sometimes not. You’d like to hope that wouldn’t be the case, but in many times, it is.”
Then there is the issue of privacy, said Alan S. Louie, research director of life sci-ence R&D strategy and technology at IDC Health Insights. “The fundamental thing that has held back the use of EHR is access to a sufficient pool of patients while main-taining HIPAA compliance,” he said.
Nevertheless, much of the online re-cruiting world is headed in the same direc-tion as ePatientFinder, exploring ways to fruitfully drill into EMR to find patients, then ask physicians to refer patients into trials. That includes Antidote, which said it will launch just such an effort this year.
360 Approach needed
Other thinkers in this space say a true revolution will take a far more widespread approach than that. Many point to com-panies like Acurion and BBK, recruitment companies that tailor their approach to each trial, using some high touch compo-nents for some, and more automated ap-proaches for others, acknowledging that no drag-and-drop solution could ever work in the world of patient recruitment.
But still others say we now have the vari-ous tools to revolutionize patient recruit-ment—with online efforts being a large part of that—but that the key lies in fitting them all together just so in the perfect eco-system, and that has yet to happen.
“Much like a puzzle, all the pieces are there, but the solution is only apparent when they are assembled correctly,” Medidata’s Kronfeld said. “Doing so will likely require devel-opment of an ecosys-tem of data, analytics, technology, services and provider organiza-tions, at a minimum. There is still a long road ahead, but we can see the pavers be-ing laid. What is less clear is how to inte-grate these data-driven insights into the work-flows of physicians in a low-friction way. There is some innovation on this front as well, but none that is large scale yet.”
As time has gone on, people have realized there isn’t one single answer that will solve the patient recruit-ment problem. “It will have to be many things that need to be put in place to get a 360 view of the patient,” he said.
And woe be to those efforts that under-mine the role of the physician and the in-dividual patient’s community of care, said Getz.
“It’s clear that recruiting efforts have to be undertaken in concert with the patient’s physician and community of care,” he said. “That relationship is absolutely essential. Anything that moves away from these re-lationships and fails to integrate runs the risk of not adequately reaching or keeping the patient.”
Getz said he’s already seeing some early signs that the industry understands that, including the marrying of investigative sites with large health systems. In doing so,
study staff can more easily move back and forth between the two environments.
“The integration of patient recruitment and retention into the continuum of care is very early stage, but there are numerous signs that the clinical research enterprise must go in this direction to remain viable,” said Getz.
Suz Redfearn is an award-winning jour-nalist and former senior staff writer for ClinPage.com. Her articles have ap-peared in numerous publications, includ-ing the Atlantic.com, the Washington Post, Slate, Salon, Politico, Men’s Health, MedPage Today and Physicians Practice. Suz holds a degree in print journalism from Loyola University in New Orleans and has been a medical writer since 1990, focusing on clinical research since 2007. Email [email protected].
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14 The CenterWatch Monthly | January 2017
Patient preferred and actual sources for information about clinical trials
Percent of total
Source: CISCRP 2015; n=12,009
51%23%
44%23%
21%30%
11%20%
19%22%
33%17%
17%21%
14%15%
16%12%
Preferred sources Actual sources
Physician
6%11%
Study sta�
Governmentonline registry
Pharmacist
Online/socialmedia
TV, newpapers
Info in doctors’o�ce
Pharma companywebsites
Family and friends
Nurse
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January 2017 | The CenterWatch Monthly 15
PipelineNews
FDA Actions
Company name Drug name Indication FDA action
Arsanis ASN100 Staphylococcus aureus pneumonia Fast Track designation granted
Neovacs IFNa Kinoid lupus Fast Track designation granted
Oragenics AG013 oral mucositis Fast Track designation granted
Theravance Biopharma velusetrag (TD-5108) symptoms associated with idiopathic and diabetic gastroparesis
Fast Track designation granted
AbbVie risankizumab pediatric Crohn's disease Orphan Drug designation granted
Biostage Cellspan Esophageal Implant esophageal implant Orphan Drug designation granted
Genexine GX-H9 growth hormone deficiency Orphan Drug designation granted
MonoSol Rx Diazepam Buccal Soluble Film (Diazepam BSF)
acute repetitive seizures Orphan Drug designation granted
PhaseRx PRX-OTC ornithine transcarbamylase deficiency Orphan Drug designation granted
Reviva Pharmaceuticals RP5063 pulmonary arterial hypertension Orphan Drug designation granted
Viking Therapeutics VK0214 X-linked adrenoleukodystrophy Orphan Drug designation granted
Seattle Genetics ADCETRIS (brentuximab vedotin)
CD30-expressing mycosis fungoides and primary cutaneous anaplastic large cell lymphoma
Breakthrough therapy designation granted
Agilis Biotherapeutics AGIL-AADC Aromatic L-Amino Acid Decarboxylase deficiency Rare Pediatric Disease designation granted
Vtesse VTS-270 Niemann-Pick type C1 disease Rare Pediatric Disease designation granted
EMD Serono, Pfizer avelumab metastatic Merkel cell carcinoma sBLA accepted for priority review
Merck (MSD) Keytruda (pembrolizumab) advanced microsatellite instability-high cancer sBLA accepted for priority review
Novartis PKC412 (midostaurin) acute myeloid leukemia Priority Review granted
Boehringer Ingelheim Jardiance (empagliflozin) reduce risk of cardiovascular death related to type 2 diabetes and established cardiovascular disease
Approved
Bristol-Myers Squibb Opdivo (nivolumab) recurrent or metastatic squamous cell carcinoma of the head and neck
Approved
Endoceutics Intrarosa (prasterone) moderate to severe pain during sexual intercourse (dyspareunia) related to vulvar and vaginal atrophy due to menopause
Approved
Genentech Avastin (bevacizumab) platinum-sensitive recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer
Approved
Genmab Darzalex (daratumumab) multiple myeloma Approved
Gilead Sciences Vemlidy (tenofovir alafenamide, TAF)
chronic hepatitis B virus infection with compensated liver disease
Approved
GlaxoSmithKline FluLaval Quadrivalent influenza vaccine Expanded indication approved
Lannett memantine hydrochloride moderate to severe dementia Approved
Medtronic Solitaire stent retriever device acute ischemic strokes Expanded indication approved
Novo Nordisk Xultophy glycemic control related to type 2 diabetes Approved
Sanofi Soliqua type 2 diabetes Approved
The following is a sampling of FDA regulatory actions taken during the previous month, compiled from CenterWatch and third-party sources including the FDA and company press releases. For more information on FDA approvals, visit www.centerwatch.com/drug-information/fda-approvals/.For custom drug intelligence reports, email [email protected].
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16 The CenterWatch Monthly | January 2017
PipelineNews
Study Lead OpportunitiesCenterWatch analyzes data in its drug intelligence database to provide advance notice of clinical trials expected to enter the next phase of clinical development soon. Contact information is provided for follow up. Sponsors/CROs: To list an upcoming trial here, contact Stephanie Hill, (617) 948-5170, [email protected]; or to initiate a search to identify sites for an upcoming or currently active trial, email [email protected] or submit online at centerwatch.com/clinical-trials/trialwatch/. Sites: To be matched to sponsor/CRO requests, submit a brief online profile at centerwatch.com/news-resources/trialwatch/. For patient enrollment support on these studies, email [email protected]. For site feasibility surveys, email [email protected].
Drug name Indication Company name Contact information
Phase I
ABBV-927 advanced solid tumors AbbVie (847) 283-8955
PDR001 plus sorafenib advanced hepatocellular carcinoma
Novartis Pharmaceuticals (888) 669-6682
SPARC001, Reference001 n/a Sun Pharma Advanced Research Shravanti Bhowmik, +912266455645 [email protected]
Phase II
ABBV-8E12 progressive supranuclear palsy AbbVie (847) 283-8955
nivolumab plus ipilimumab metastatic castration-resistant prostate cancer
Bristol-Myers Squibb [email protected]
CHF6001 chronic obstructive pulmonary disease
Chiesi Farmaceutici [email protected]
GanMaoKangNing Granules epidemic influenza in Beijing Dalian Zhen-Ao Bio-Tech [email protected]
M2951 relapsing-remitting multiple sclerosis
EMD Serono Research & Development Institute
M2951 systemic lupus erythematosus EMD Serono Research & Development Institute
RNS60 amyotrophic lateral sclerosis Revalesio www.revalesio.com/contact-us
VIS410 uncomplicated influenza Visterra (617) 498-1070
Phase III
AG-120 advanced/metastic cholangiocarcinoma
Agios Pharmaceuticals (844) [email protected]
ASP1517 chronic kidney disease Astellas Pharma [email protected]
rucaparib metastatic castration-resistant prostate cancer
Clovis Oncology [email protected]
Budesonid moderate to severe allergic persistent rhinitis in Brazil
Eurofarma Laboratorios Alexandra Dumont, +5519 3789-8600 [email protected]
NI-071 rheumatoid arthritis Nichi-Iko Pharmaceutical [email protected]
n/a spinal muscular atrophy in South African
Roche Itumeleng [email protected]
isatuximab, pomalidomide, dexamethasone
plasma cell myeloma Sanofi [email protected]
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January 2017 | The CenterWatch Monthly 17
CLINICAL TRIAL COLLABORATIONSImplementing solutions to drive greater efficiencies in outsourcing R&D operations
The 2nd Annual strategic conference will focus on key areas of collaboration including:
■ Technology partnerships ■ State of collaboration in the clinical trials enterprise with healthcare partners ■ Future collaborations to drive greater efficiencies in R&D operations
April 3-4, 2017 Renaissance Boston Waterfront Hotel
SAVE THE
DATE
REGISTER www.TheConferenceForum.org (646) 350-2580 15% off for CenterWatch readers with code CW17
“The Conference explores new and interesting collaborations to advance drug development.“
Drug name Indication Company name Contact information
Continued from Phase III
NETILDEX cataracts SIFI Aldo Caporossi, 00390630155228 [email protected] Rita Blanco, 00390957922201 [email protected]
Phase IV
n/a pharmocogenomic testing for medication management
MD Global Inc. Dave Brewer [email protected]
Rivastigmine Alzheimer's disease Novartis Pharmaceuticals +41613241111
BST-CarGel scaffold with microfracture
cartilage lesions of the femoral condyle
Piramal Healthcare Canada David A. Pogorzelski, 289-337-0857 [email protected] Sprague, 905-929-7846 [email protected]
Alogliptin type 2 diabetes mellitus Takeda (877) [email protected]
Multi-phase Trials
apixaban pediatric congenital or acquired heart disease
Bristol-Myers Squibb, Pediatric Heart Network
TRC253 metastatic castration-resistant prostate carcinoma
Tracon Pharmaceuticals [email protected]
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New Drugs in the PipelineThe following drugs were added to CenterWatch’s Drugs in Clinical Trials Database during the previous month. For additional information, please visit centerwatch.com/drug-information/pipeline/. Note: The database is a subscriber-only service. To request a free trial, you may visit centerwatch.com/drug-information/demo/. CenterWatch also prepares custom drug intelligence reports that cover a variety of medical conditions. Email [email protected].
Phase Drug name Indication Company name
preclinical BTX-1503 acne Botanix Pharmaceuticals
I ABI-H0731 hepatitis B Assembly Biosciences
I ATX2417 chronic respiratory disease Chiesi Farmaceutici
I ELX-02 mucopolysaccharidosis type 1 Eloxx Pharmaceuticals
I IMR-687 sickle cell anemia Imara
I PNT737 solid tumors ProNAi Therapeutics
I RV521 RSV infection ReViral
I SYNT001 IgG-mediated autoimmune diseases Syntimmune
I TTI-621, SIRPαFc hematologic malignancies, solid tumors and mycosis fungoides
Trillium Therapeutics
I VX-659 cystic fibrosis Vertex
Ib CT1812 Alzheimer’s disease Cognition Therapeutics
I/II GX-H9 growth hormone deficiency Genexine
I/II GC1123, idursulfase-beta ICV Hunter’s syndrome Green Cross
I/II IMG-7289 hematological malignancies Imago BioSciences
I/II AstroRx, astrocyte stem cell therapy ALS Kadimastem
I/II SB-061 osteoarthritis Symic Biomedical
II GX-188E HPV-associated disease Genexine
II selonsertib nonalcoholic steatohepatitis, pulmonary arterial hypertension and diabetic kidney disease
Gilead Sciences
II MK-3682B hepatitis C Merck
II OMS405 drug addiction and substance abuse Omeros
II RT-100 RSV infection Renova Therapeutics
II SNF472 calciphylaxis Sanifit
II VX-152 cystic fibrosis Vertex
II VX-440 cystic fibrosis Vertex
IIb CryoVax cancer immunotherapy Immunovative Therapies
II/III lemborexant insomnia and sleep disorders related to Alzheimer’s disease
Eisai
FDA Approved Intrarosa postmenopausal women with vulvar and vaginal atrophy
Endoceutics
FDA Approved Soliqua 100/33 type 2 diabetes Sanofi
18 The CenterWatch Monthly | January 2017
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January 2017 | The CenterWatch Monthly 19
CenterWatchPulse
The Pulse on Global TrialsThe recent unveiling of OpenTrials.net
marks an important milestone in the de-mocratization of data. Bringing together
multiple sources of clinical research informa-tion, from ClinicalTrials.gov, PubMed, EU CTR, WHO ICTRP and many others, this search engine promises to bring citizen science further into the mainstream.
Citizen science—scientific research conducted, in whole or in part, by amateur or nonprofessional scientists—represents a new frontier for clinical research. In a field that has well-established norms and methods, crowdsourcing necessitates the research sector to embrace a new mindset.
Today, data is ubiquitous, but it’s not visible to everyone. This limits the ability of patients, caregivers and healthcare professionals on the front lines of patient care from contributing good ideas to the advancement of science. In the future, clinical research will be powered by a far-reaching data infrastructure, much like an energy grid, where anyone plugged in can be both a consumer and generator of data.
SERMO, a professional online network of more than 600,000 healthcare profession-als worldwide, is a good illustration of this model. In Canada, E. coli had killed a boy and two weeks later his sister presented with the same symptoms. Her doctor posted the case to SERMO, asking for input. Within hours, 46 doctors globally helped solve the case.
The ability to aggregate independent data points from multitudes of people has dem-onstrated effectiveness in other real-world applications. In 1999, world champion Garry Kasparov played a game of chess over the internet against a group of 50,000 people across 75 countries. A very close game, with Kasp-arov ultimately prevailing, the event revealed the power of crowdsourcing. While no single person could have competed that well against the expert, the combined knowledge of tens of thousands made for a formidable competi-tor. When responding to Kasparov’s moves,
each person on the world team drew upon their individual experience. If one person had seen a particular pattern or con-figuration of the board, that knowledge rose to the top and was acted upon.
Over the course of the last two decades, clinical research has seen growing benefits from the application of crowdsourcing. In fact, PubMed now includes hundreds of crowd-sourced studies. One example is an open chal-lenge to find solutions to estimate the progres-sion of Amyotrophic Lateral Sclerosis (ALS). The competition, with an award of $50,000, drew 37 groups from around the world—many with no ALS experience—to create better predictive tools that could make it easier to test new medications and their impact. The fresh thinking and alternative perspectives generated through crowdsourcing helped identify com-parative strengths of competing methods.
In another study, scientists evaluated the viability of crowdsourcing to build data sets through the public health forums MedHelp and CureTogether. They found that crowd-labeled data was significantly more accurate than expert-labeled data (84% vs. 78%).
The most interesting changes, though, are when the public at large begins to harness the ubiquity of data to fuel humans’ ability to ad-dress unresolved scientific challenges. In this context, patients, caregivers and communities of shared purpose have found success initiating their own scientific inquiries.
Using the online platform PatientsLikeMe, two patients from Brazil and the U.S. with advanced-stage ALS recruited 149 patients with ALS to take lithium in order to test its effects on disease progression and symptom allevia-tion. The PatientsLikeMe ALS study, which was completed over eight months, was eventually published in Nature Biotechnology and pro-vided the impetus for a standard clinical trial.
In another example, parents of children suffering from Niemann-Pick Type C, an extremely rare lipid storage disease, led to extensive negotiations with the FDA for permission to administer cyclodextrin to their children, first intravenously, and then eventually directly into the spinal fluid. Their pursuit of a cure led to a phase I clinical trial of cyclodextrin.
Perhaps one of the most compelling stories is that of Dr. David Fajgenbaum, a young physician who became the patient, then lead researcher on a mission to cure Castleman’s disease. After nearly dying not once but five times from the disease, Fajgenbaum gave up his budding career as an OB-GYN to take residence at the University of Pennsylvania and form the Castleman Disease Collaborative Network (CDCN). Connecting hundreds of expert and non-expert researchers around the world through an online portal, he has been able to crowdsource a list of possible Castle-man studies, prioritize them and fund about 20 different studies.
The implications of crowdsourcing for clinical trials are numerous. From developing study hypotheses, improving study design and optimizing analysis of data generated from study, to fundraising for underserved diseases, collaborating with peers and the public and increasing participation in clinical research, crowdsourcing represents a fundamental shift in global clinical research.
Matthew Howes is executive vice president, Strat-egy & Growth for PALIO, an inVentiv Health company. [email protected].
One type of medical research crowdsourcing:1. There is a disease indication, trial or medical issue2. The indication or trial is broadcast online3. An online “crowd” submits solutions4. Researchers jointly vet solutions5. Key solutions rise to the top for a diagnosis or further research
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