New Infographic: Why choose open-source EDC?

May 3, 2013 by Clinovo    No Comments    Posted under: EDC, New Technologies, Trends

This infographic is a visual and appealing way to understand why open-source Electronic Data Capture (EDC) is an alternative of choice to proprietary systems or paper-based studies. Do you own a website, a forum or a blog on clinical trials or Electronic Data Capture (EDC) ? You are invited to share this infographic  with your readers! How? Simply copy this code to your page: <a href=”http://blog.clinovo.com/new-infographic-why-choose-open-source-edc/”><img alt=”Infographic: Why choose open-source EDC?” choose=”open-source=” src=”http://blog.clinovo.com/wp-content/uploads/2013/05/infographic-2-resized.png” style=”height: 1817px; width: 675px;” why=”" /></a>[Source: <a href="http://blog.clinovo.com" title="Infographic: Why choose open-source EDC?">eClinical Trends by Clinovo</a>]

Challenges and benefits of EDC adoption

Apr 26, 2013 by Clinovo    No Comments    Posted under: EDC, Trends

Clinical research is one of the most expensive areas of drug development. Bringing an approved new drug from initial private investment to a patient takes over 13 years and $1.3 billion, or an average of $146 million per year.¹

Industry data shows clinical trials costs are growing across all development phases. A 2011 report, Clinical Operations: Benchmarking Per-Patient Costs, Staffing and Adaptive Design by Cutting Edge Information, tracked costs for 100 trials across multiple therapeutic areas finding that per-patient clinical trial costs rose an average 70% from 2008 to 2011.² The largest increases occurred in Phase IIIa and Phase IIIb. Phase I trials are also suffering from cost inflation, with per-patient costs increasing by an average 46% over the same time period.³

Electronic Data Capture (EDC), which collects clinical trial data electronically rather than on paper, is becoming an increasingly popular solution for streamlining data processing. This white paper will review benefits that EDC brings, extending beyond, and contributing to, cost-efficiency. It will also discuss challenges and limitations that sponsor companies can expect when implementing EDC solutions in clinical research.

Key benefits of Electronic Data Capture

1. Cost-saving: Forrester Research analyzed cost-savings to Novartis, which has utilized a customized open-source EDC system for over 400 clinical trials. For a 12-month Phase II clinical trial with 20 sites and 10 patients per site, the operational savings were substantial: $347,600.⁴

Figure 1. Forrester Research Paper versus EDC cost comparison.⁵

The cost of the clinical trial was reduced from $732,000 to $384,000 thanks to remote monitoring, fewer site visits, shorter patient recruitment times, reduction (or elimination) of printing costs, faster data entry, and lower data cleaning costs.⁶ Visit-related costs were reduced by 50%, data cleaning costs by 80%, and all other operational expenses by 32%.⁷

Overall, Novartis claimed a savings of approximately $17 million by no longer needing to print CRFs on NCR paper, a necessity in paper-based trials, which represented $42,500 per Novartis study analyzed.⁸ If we consider that printing costs run as high as $100 per casebook, a study with 500 patients would cost up to an estimated $50,000 prior to factoring in staffing costs for casebook preparation, without accounting for shipping.

2. Time-saving: Single data entry—which replaces the completion of paper CRFs followed by double data entry—remote monitoring, and reduction in the number of queries each save a considerable amount of time. Overall, they have been calculated to reduce the duration of clinical development by up to 30%.⁹

It is critical to note that the most significant time-savings occur during database lock. It has been shown that, when it is time for database lock, there is less missing data and fewer errors and queries with EDC than with paper-based systems. As shown in the table below, database lock can take as long as nine days with paper, whereas database lock is performed in only one day with an EDC system.

Figure 2. Time savings.

3. Cleaner data and reduced queries: EDC adoption leads to a dramatic reduction in the types of data errors found in paper-based CRF studies, such as out-of-range values and missing data. In addition, errors can be detected and corrected much earlier in the clinical trial with EDC than with paper-based systems that can only rely on ad hoc mid-study analysis. EDC edit checks are automatic and visible at the time of entry and are therefore resolved immediately, resulting in cleaner data at time of entry in database.

A case study led by Applied Clinical Trials compared a paper query management system with an EDC system using edit checks and found a 65% reduction in the number of queries.¹⁰

Figure 3. Reduction of the number of queries.¹¹

4. Traceability: Title 21 Code of Federal Regulations Part 11 (21 CFR Part 11) is the United States Federal Regulation which applies to electronic records and electronic signatures in clinical systems.¹² EDC systems must track all data changes in audit trails in order to be 21 CFR Part 11 compliant. Vendors must also plan for disaster recovery and analyze and remedy potential risks. It is critical to note that answering FDA reviewers’ questions is made easier by EDC systems as they can track any changes automatically.

5. Simplified monitoring: Remote monitoring enabled by EDC systems drastically lowers the cost of monitor visits. EDC enables early identification of discrepancies or data entry errors, minimizing the time spent by monitors at sites. Estimating that a visit can cost up to $3,000, the total savings for a study with 20 sites can reach $60,000.

6. Reduced data entry: With paper-based systems, clinical data must first be written on paper and then double-data entered into a central system, which is a time-consuming and error-prone process. Electronic Data Capture’s Impact on Late Phase Research by Dr. Hugh P. Levaux claims that, when considering manual double-data entry costs can be as high as $3 per page, a 100-page casebook can cost as much as $300. These figures translate to a cost of $150,000 for a 500-patient study.¹³ EDC applications necessitate only single-data entry since data entry occurs directly at the site and is the equivalent of CRF completion on paper.

7. Reactivity: Some EDC systems provide real-time alerts and reports, giving decision makers instant access to critical data. ClinCapture by Clinovo recently introduced LiveReports^TM to provide a real-time overview of the clinical trial. Real-time reports enable decision makers to be more proactive in identifying bottlenecks such as late sites, and to be more reactive to data to ensure patient safety.

Ultimately, EDC systems enable sponsors to make efficacy and/or safety determinations earlier in the drug development process. EDC enables pharmaceutical, biotechnology, and medical device industries to focus on the development of the best drug, biologic, or device candidates that will most benefit patients, saving time and millions of dollars in drug development.

8. Reusability: A characteristic of EDC is the ability to reuse the system in future studies which lowers the cost of EDC adoption in the long run. Once forms and their associated edit checks are created, they can be stored in a library and reused for an infinite number of studies. In a case study from Clinovo, a leading global technology medical device company was looking to efficiently manage large amounts of data while staying on-time and on-budget.¹⁴ Clinovo trained the sponsor’s staff to build its studies on the open-source EDC system ClinCapture, enabling the sponsor to customize the ClinCapture platform and roll out nine additional studies themselves. In addition, the sponsor was able to host the system in-house, thereby avoiding vendor lock-in and retaining full control over their clinical data.

9. Mid-study changes: EDC systems make mid-study changes such as the addition of new fields in a Case Report Form (CRF) much smoother than do paper-based studies. Some EDC systems support CRF versioning to automatically update all CRFs in selected sites in just a few seconds.

10. Patient Safety: Improved data quality, better reactivity, and reduction in study time themselves contribute to the faster delivery of better medications. Some specific EDC features have an even bigger impact: faster notification of adverse events, for example, can help with earlier and better decision-making, potentially saving hundreds or thousands of patients from exposure to unsafe medication.

Limits and difficulties of EDC adoption

Despite the tangible benefits of Electronic Data Capture, the adoption of EDC systems has remained slow in some segments of clinical research. Only 40% of Phase I clinical trials had adopted EDC by the end of 2012.

Clinical trial experts suggest this slow adoption is explained by the high cost of proprietary EDC systems and by the structural changes and learning curves incurred by sponsor companies when implementing an EDC system. Some attribute low adoption rates to negative impressions of early EDC systems based on poor design and limited performance.

There is a common perception that paper-based studies are faster and less expensive to implement than are EDC studies. It is undoubtedly true that studies can be started faster on paper. But data shows that their overall duration is as much as 30% longer on average.¹⁵

EDC vendors are making an effort to minimize the study-build time by leveraging reusability and automation. It is now possible to deploy a full EDC study in days rather than the weeks or months historically, assuming study form reusability.

The initial cost of EDC is also a major determent to its adoption, especially for preclinical or Phase I trials with lower budgets. The most significant costs are incurred when hiring vendor(s), assigning clinical and data management experts to interface with programmers, and setting up internal computer systems, including the purchase of hardware and software. Following these initial setup phases, subsequent study costs for each new clinical trial can become marginal, leaving mostly fixed annual fees for system maintenance, including optional hosting fees.

Finally, data privacy and security is also a major concern among trial investigators. A study by Silico Research shows that investigators cite security and confidentiality as key concerns when conducting EDC-based clinical trials.¹⁶ It is essential to select EDC vendors who thoroughly follow regulations and offer secure hosting services with data redundancy ensuring full disaster recovery.

Figure 4. Trial investigators concerns on EDC-based clinical trials.¹⁷

Among other concerns, sponsors also worry about the steep learning curve and heavy training needed to switch to an EDC system. The implementation of an EDC system drastically changes the structure and the processes within a sponsor organization. EDC vendors are aware of these difficulties and are focusing on improving EDC systems’ ease-of-use. Vendors are also putting an emphasis on training sessions for end users as well as on ensuring reactive support services.

Moreover, one can observe standardization in the user interface guided by consensus-based collaborative standards like CDISC/CDASH, allowing for consistent user experience across vendors and studies and thereby requiring less training to adapt to new study screens.

Conclusion: Planning EDC deployment, a key success factor

A potential steep learning curve for clinical research teams, structural changes in organizations, and perceived high cost of EDC implementation are some of the legitimate reasons to hesitate before adopting EDC. However, considerable time- and cost-savings, along with drastic data quality improvement outweigh these difficulties.

It is necessary for sponsors to put controls in place to ensure data quality and integrity throughout their clinical trials. This can and is done with paper-based clinical studies, but often with unintended negative consequences, including delay and looping in the data entry process. With EDC, edit checks are integrated from the start and are seamlessly activated during data entry, ensuring that the sites, which are responsible for providing study data, can address most issues on the spot.

In order to fully benefit from EDC systems, it is critical for sponsors to plan ahead. Most importantly, planning must be carried out prior to study build. Data entry screens, online edit check specifications, and the annotated case report form (aCRF) must be implemented before the study goes live.

Though the process changes as it evolves, Electronic Data Capture brings complete and up-front integration of the trial design and setup to the different operational groups involved, including Clinical Operations, Clinical Data Management, and Biostatistics, thus ensuring not only that the data entry process is easy and well-customized for the clinical sites, but also that the final database exports will be fully compliant and meet analysis requirements.

Olivier Roth, Marketing and Communication Coordinator, Clinovo

References

1. Herper, M. The Truly Staggering Cost of Inventing New Drugs. Forbes website. http://www.forbes.com/sites/matthewherper/2012/02/10/the-truly-staggering-cost-of-inventing-new-drugs/. February 2012. Accessed April 9, 2013.
2. Per-Patient Clinical Trial Costs Rise 70% in Three Years. Cutting Edge Information website. http://www.cuttingedgeinfo.com/2011/per-patient-clinical-trial-costs/. July 2011. Accessed April 8, 2013.
3. Ibid.
4. Peachey J, Spink C, Fraser H, Henderson S. The eClinical equation: Part 1: Electronic Data Capture. IBM Global Business Services: IBM Institute for Business Value. 2005; 3. http://www-05.ibm.com/de/healthcare/literature/eclinical-equation-1-lang.pdf. Accessed April 8, 2013.
5. Ibid.
6. Ibid.
7. Ibid.
8. Ibid, 3-4.
9. Green, J. Realising the value proposition of EDC. Innovations in Clinical Trials. September 2003; 13. http://www.iptonline.com/articles/public/ICTTWO12NoPrint.pdf. Accessed April 8, 2013.
10. Mitchel J, You J, Lau A, Kim Y. Paper vs. Web: A Tale of Three Trials. Applied Clinical Trials: Internet Insight Section. August 2001; 1. http://www.medchannels.com/pdfs/whitepapers/ACTArticle.pdf. Accessed April 8, 2013.
11. Ibid.
12. Part 11, Electronic Records; Electronic Signatures – Scope and Application. U.S. Food and Drug Administration website. http://www.fda.gov/regulatoryinformation/guidances/ucm125067.htm. March 23, 2009. Accessed April 9, 2013.
13. Levaux, H. Electronic Data Capture’s Impact on Late Phase Research. Business Briefing: Pharmatech. 2004. http://www.touchbriefings.com/pdf/890/PT04_Ninaza.pdf. Accessed April 8, 2013.
14. Clinovo Case Study: Open Source EDC Unmatched Cost-efficiency. Clinovo website. August 28, 2012. http://www.clinovo.com/userfiles/clinovo-open-source-edc-unmatched-cost-efficiency.pdf. Accessed April 8, 2013.
15. Green, J. Realising the value proposition of EDC. Innovations in Clinical Trials. September 2003; 13. http://www.iptonline.com/articles/public/ICTTWO12NoPrint.pdf. Accessed April 8, 2013.
16. Peachey J, et al. The eClinical equation: Part 1: Electronic Data Capture. IBM Global Business Services: IBM Institute for Business Value.  2005; 9. http://www-05.ibm.com/de/healthcare/literature/eclinical-equation-1-lang.pdf. Accessed April 8, 2013.
17. Ibid.

Thank you Note

• Jean Maupas, Director of Operations, Clinovo
• Dave Alderson, Senior Director of Sales, Clinovo
• Anil Kishan, Marketing Assistant, Clinovo
• Maxwell Love, Business Development, Clinovo

Launch of Users and Developers Community for ClinCapture

Mar 28, 2013 by Clinovo    No Comments    Posted under: EDC

Open Source Technologies for Clinical Trials

May 30, 2012 by Clinovo    No Comments    Posted under: Business Best Practices, EDC, Trends

Clinical trials have become increasingly complex and, as a result, costly. Only 333 drugs and biologics have been approved between 2000 and 2010 due to stricter regulatory procedures while spending has increase by 15 in the same period of time.

The need for innovation is critical in the pharmaceutical and biotechnology industry. Life science companies and service providers are looking for innovative solutions to improve study performance and minimize their risks. This article will demonstrate how open source technology presents an innovative solution to this challenging environment, and ultimately helps bring medical innovations faster to patients.

What is open source? Open source is a type of software license. There are various types of open source licenses, but the common characteristic to all is allowing free distribution of the underlying source code. Famous open source systems include Linux, Apache, MySQL, and many others. Below is a definition of Open-Source Software:

1. Free redistribution
2. Source code
3. Derived works
4. Integrity of the author’s source code
5. No discrimination against persons or groups
6. No discrimination against fields of endeavor
7. Distribution of license
8. License must not be specific to a product
9. License must not restrict other software
10. License must be technology-neutral

Taken from Opensource.org. See http://opensource.org/docs/definition.ph​p for an annotated description of the above points.

Open Source in the Clinical Trial Industry. Two pioneers in open source technology for clinical trials are Cynthia Brandt and Prakash Nadkarni of the YaleCenterfor Medical Informatics, with their TrialDB system (http://ycmi.med.yale.edu/trialdb/), an open-source Clinical Study Data Management System (CSDMS) for the storage and management of clinical data initiated in the 1990’s.

The US National Cancer Institute launched a wide-ranging, open-source friendly initiative named CaBIG (Cancer Biomedical Informatics Grid - https://cabig.nci.nih.gov), that aims to develop a collaborative information network to accelerate the detection, diagnosis, treatment, and prevention of cancer.

Open source software is also used for electronic data capture (OpenClinica, ClinCapture), clinical research (LabKey Server), Electronic health or medical record (OpenEMR), analysis (R project), and CDISC conversion (CDISC Express, OpenCDISC).

Benefits of open source technologies for clinical trials. While open source is prevalent in many industries, this technology is still emerging in the field of clinical trials. The development of open source technology in the clinical arena has been quickly growing. Eric Morrie, Manager for Clinical Programming in one of the worldwide leading medical device companies, shared his extensive experience on open source technologies at a Silicon Valley BioTalks (http://www.clinovo.com/biotalks/open-source/article). Eric explained how open source technologies save time, improve re-usability and simplify the customization of systems to a company’s needs.

• Provide state-of-the-art, cost-effective solutions

Proprietary systems for clinical data management are often too expensive for individual researchers and smaller companies. As a result, they often use slow, error-prone paper-based methods.

Ale Gicqueau, President and CEO of Clinovo, a CRO based in the Bay Area, explains that with open source technologies, the license fee for proprietary systems is no longer a barrier entry for small and mid-size companies (http://www.clinovo.com/biotalks/open-source/article). Open source clinical data management systems save money by eliminating the reliance of using expensive proprietary systems, while insuring the same levels of quality. It provides a means for smaller companies to access high quality technologies for clinical data management and comply with international regulatory standards.

• Avoids the risks of vendor lock-in

Proprietary systems lock a customer into a vendor’s product from which they cannot escape without substantial switching costs. Such dependence includes reliance for maintenance and support, and the necessity to accept version upgrades that the buyer may not need.

Widely adopted open source systems on the other hand have multiple vendors supporting it. Surveys demonstrate that early adopters of open source technologies are driven by the “reduced dependence on software vendors”, often seen as one of the most important advantages of open source technology.

• Enables a larger community to maintain and enhance the source code

The open source model enables quick improvements by giving access to the underlying source code to a large community of talented developers. In the open source community, developers are encouraged to produce derived works to enhance the existing source code.

“The Open Source community attracts very bright, very motivated developers”, explains the UK software consultancy company GB Direct (http://open-source.gbdirect.co.uk/migration/benefit.html). “Highly prized factors are clean design, reliability and maintainability, with adherence to standards and shared community values preeminent.”

A rising trend: Open source for electronic data capture: One of the most famous and number one open source system for clinical trials is OpenClinica, with a community of over 12,000 developers.EDC systems are often prohibitively expensive, ranging in the hundreds of thousands of dollars. As a result, open source technology has been particularly well-received in the field of electronic data capture. Open source EDC platforms deliver the same benefits as proprietary EDC systems but without the license fee.

The one I am most familiar with is an open source EDC system developed by Clinovo : ClinCapture. It is a validated and enhanced version of the #1 open source EDC platform, fully customizable to any clinical study. Learn more

This open source EDC system has been successfully implemented by major pharmaceutical, medical device and biotech companies. Victor Chen, Director of Clinical Affairs at Intuitive Surgical, explains that he decided to use this technology due to the low price and the flexibility that suits adaptive clinical trials. However, he emphasizes on the importance of rigorously assessing any open source system vs. proprietary systems and evaluating the cost for validation. Read case study

The emergence of open source based tools for CDISC: Converting clinical data to the widely recognized CDISC SDTM standard is often done manually, which can quickly become tedious, error-prone, and time-consuming.CDISC SDTM data is the standard format recommended by the FDA for clinical trial data submission. The mission of CDISC is to develop and support global, platform-independent data standards to improve medical research.

Clinovo developed an open-source system to help with this conversion to CDISC SDTM: CDISC Express. CDISC Express is a powerful open source SAS®-based system that automatically converts clinical data into CDISC SDTM using an Excel framework.

The CDISC Express framework is highly extensible. The system significantly speeds-up CDISC SDTM conversion, and has been successfully implemented for major biotechnology and pharmaceutical companies. Download for free

Conclusion: Today, it takes on average 10 to 15 years to develop a drug and costs near $1.2 billion. With only 2 of 10 marketed drugs returning revenues that match or exceed R&D costs, developing medical innovations has become more and more risky. Open source technologies are an innovative way to lower the cost of clinical trials and minimize risk, while ensuring the same level of quality as proprietary systems.

Ultimately, open source technologies increase the scope and variety of clinical trials, by enabling smaller institutions to pursue their clinical research that would otherwise be out-of-reach and beyond financial capacity. “We believe that an open-source approach has the best chance of ensuring that all kind of groups can be involved with the development of systems that have bearing on global public health”, explains Greg W. Fegan and Trudie A. Lang in their featured article Could an Open-Source Clinical Trial Data Management System Be What We Have All Been Looking For?

Read our latest white papers now

References

• Silicon Valley BioTalks, June 2011 : http://www.clinovo.com/node/129
• “Could an Open-Source Clinical Trial Data Management System Be What We Have All Been Looking For?”, By Greg W. Fegan and Trudie A. Lang, March 4, 2008
• “Overcoming Obstacles To Successful Clinical Trials through Open Source”, by Benjamin Baumann, Nov 10, 2011
• 2011 profile, PhRMA Pharmaceutical Industry
• Opensource.org
• https://cabig.nci.nih.gov
• http://ycmi.med.yale.edu/trialdb/
• http://open-source.gbdirect.co.uk/migration/benefit.html
• Health Decision Webinar “Top 10 Benefits of Adaptive Design”, Jan 25, 2011

Download

• CDISC Express: www.clinovo.com/cdisc
• ClinCapture brochure: http://www.clinovo.com/resources/brochures/clincapture
• Clinovo case studies on open source systems: http://www.clinovo.com/case_studies

Silicon Valley BioTalks

Jun 15, 2011 by Clinovo    No Comments    Posted under: Best-Practices, Code, EDC, Menu, OpenClinica

We are organizing a networking event on open source technologies for clinical trials : Silicon Valley BioTalks ‘Run efficient clinical trials with open source techonlogies’

We noticed that the interest for open source technologies and practices has been growing in the clinical trial and biotech sectors.

The most frequent questions seem to be : What are the key benefits of open sources technologies for sponsors? What are the different open source products available today for clinical trials? What are the best practices for a successful implementation?

Representatives of Abbott Vascular, Intuitive Surgical and Clinovo will share their experience with open source technologies.

The event is taking place on June 29th in Palo Alto

You will find all details and the online registration form here