Dealing with antibiotic resistance is important—and the subject received lots of attention in November, during different manifestations of the annual antibiotic resistance event around the world. But just as important—and probably more so—is the related question of how to stimulate development of new antibiotics. A workshop at the European Medicines Agency witnessed Andrzej Rys, a senior European Commission official, urge "further action" at policy level in Europe, including making the best use of medicines legislation to bring new antibiotics to patients. In order to do so, it was necessary, he suggested, to bring greater clarity, flexibility and speed to the authorization procedures for the approval of new products, and to look again at the way that the risk-benefit equation is calculated. 

At the same meeting, Barry Eisenstein, now head of scientific affairs at Cubist, and a former Lilly research boss, underlined the need for "greater trial feasibility and regulatory predictability." Speaking on behalf of the European drug industry at the EMA meeting, he urged adoption of a tiered approach to authorization that would allow earlier approval for antibiotics.  

He pleaded for using the totality of evidence for antibiotic approval and for setting interpretive breakpoints. Suggesting that pharmacodynamics can provide a valuable guide, he contended that if safety is good in Phase I and II, "you probably have a drug." He also called for measures to facilitate small research programs.  

Sally Davies, the UK's Chief Medical Officer, has been one of the most vigorous advocates of stimulating antibiotic research, issuing apocalyptic warnings about the need for action. Earlier this year she highlighted a "discovery void" with few new antibiotics developed in the past two decades, leaving the "armory nearly empty as diseases evolve and become resistant to existing drugs."  

Davies told this columnist during November that governments around Europe should be more energetic in pushing academia into action, and in promoting collaboration with industry.  "Academia on its own doesn't know enough about development paths, so tie-ups with industry are vital," she said. Companies at present do not get engaged because of the lack of incentives, and this has to be dealt with, she insisted. In her view, the public-private partnerships such as the European Innovative Medicines Initiative (IMI) are "a good start." But she also urged examination of other approaches, such as the use of transferable patent vouchers, or even paying more for antibiotics. Within Europe, she said that Sweden and Norway are proving strong allies in the bid to boost research—but that not every European country shares the enthusiasm. "We have work still to do to educate the countries in Eastern Europe," she added. 

Meanwhile, the Swedish government allocated nearly $40 million for research on infection and antibiotics over the next four years. Roche said in November that it would resume the development of antimicrobial drugs, while taking over an experimental drug, developed with EU funding, by Polyphor. And IMI has announced plans to conduct clinical trials with innovative anti-infectious agents, using new trial designs, across a new network it has set up of nearly 300 clinical sites across 34 countries. 

A broad coalition of national research institutions has put the development of novel antibiotics at the head of the agenda it is now finalizing under a "Joint Program Initiative on Antimicrobial Resistance," which brings together the larger EU member states, along with Canada, Israel, Turkey, and Norway.  

In the initiative's scientific advisory board foreward to the draft research agenda, it stresses combining the efforts of the industry, public health bodies, and academic bodies.  

In addition to the scientific dimension, "it is essential that regulatory processes are streamlined and economic barriers are lifted to allow the rapid and successful introduction of novel antibiotics and antimicrobials to the market." 

Marco Cavaleri, head of anti-infectives and vaccines at the EMA, accepts that regulators could offer advice and liaison "to maximize the chances of regulatory success" for public-private partnerships projects. even though "due to conflict of interest it is not appropriate to take an active part in this kind of initiative."  

 is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium. 

Articles

View from Brussels

Global action and collaboration is needed to tackle the threat of antibiotic-resistant diseases.

On Trial—Europe's Response to Antibiotic Research Gap

There have been significant changes in the way clinical trials are executed today—with a move towards eClinical where technology-based solutions are being widely used to drive automation and overall efficiency into the clinical trial end-to-end process. The majority of these current approaches are more siloed around systems such as CTMS, EDC/CDMS, IVR and submissions management (i.e., trial master file, CSR, etc.). There still exists certain phases such as study design and study build within the clinical trial process that can have a significant impact based on reduction in overall time for getting trials ready for study execution across the clinical sites. 

This article provides a framework called clinical trial design automation that helps establish a recommended approach to manage the study design and study build phase of the overall clinical trial process. The approach includes process and technology to aid in speeding up critical elements of a clinical trial lifecycle—elements covered are from study design (protocol design) to study build. This article highlights how this recommended approach will drive efficiencies by reducing overall timelines for building eCRF-based clinical trials including the drive towards reusing protocol elements and eCRF page elements using standards-based libraries. The conceptual architecture provided describes the components of the architecture and the process upon which this recommended approach for clinical trial design is founded on. Most of the components necessary for the proposed approach can be configured based on pre-existing solutions in the marketplace, while the core component termed clinical design interchange doesn't exist and will need to be designed and built. The use of industry data standards and CDISC-based messaging format for storing and communicating is proposed. The key mechanism in the proposed approach is the creation and maintenance of study components which are constantly being built in a clinical library resulting in reusable components that enables flexibility and adaptability to changing needs/regulatory requirements and support for global clinical trial execution. 

This recommended approach has significant value for key clinical trial stakeholders—sponsors, CROs, and eClinical vendors, each with the potential for driving efficiencies in the study design and study build phases of clinical trials resulting in the overall cost reduction of clinical trial execution while enabling flexibility to meet new regulations and clinical trial trends. 

Life science organizations are facing challenges with escalating costs emanating from increased operational complexities and ever-changing regulatory requirements within the United States and across the globe. In many cases, primary increases in costs for bringing products to market are around planning and execution of clinical trials. Further, the clinical trial market place is experiencing the following key trends as a result of increased cost of drug development, reduced probability of drug success, and failure to meet trial deadlines due to trial operational complexities. 					

Maturity of CRO's, emergence of boutique CROs, and other support organizations.

  complete drug development faster than the drug companies themselves, without sacrificing data quality. Boutique CROs are focusing on specific therapeutic areas and provide expertise such as protocol design, patient/investigator recruitment, etc. 

Globalization impact has increased clinical trials being conducted outside of United States and Europe.

 It has been driven by reduction in costs, increased patient recruitment across varying demographics, and less bureaucracy.

 Eighty-nine percent of all drug candidates from the initiation of Phase I through FDA approval fail in the clinic. Adaptive trials offer the potential to enable more levels of doses to be studied using maximum tolerated dosage over a select patient population.

  Adaptive trials improves the decision making in the identification of drugs with reduced probability of success.

  by identifying patients that meet clinical protocol criteria. Clinical data captured via these methods are helping answer questions about the safety, effectiveness, and costs of new treatments.

The proposed approach is based on building clinical studies centered on the following steps: 					

Developing study/protocol based on individual protocol components that are stored in a reusable CDISC-based repository.

Designing individual eCRF page elements that are stored in a eCRF library.

Leveraging study maps which define eCRF pages based on linking eCRF page elements to study/protocol components.

Building entire eClinical studies based on study maps.

The intent of the proposed approach is to enable the reduction in cycle times based on process improvements including reuse of clinical trial design content (study design and study build) while providing for a flexible framework that adapts to meet clinical protocol needs (Figure 1). 

Each of the key components of proposed solution architecture is described in detail below: 

 This component is based on document management solutions that provide structured authoring,

  wherein complex documents are broken down into smaller components and then assembled together via document maps to create final published documents in multiple formats. In the case of clinical trial protocols, it is based on decomposing clinical trial protocols (includes protocol amendments) into components and building protocol components independently and then assembling these components into protocol documents using pre-defined protocol document maps. All these components are stored in a document store called the protocol repository that serves as the primary content storage mechanism for managing protocol components. The protocol repository is based on the protocol representation model (PRM)—a CDISC standard that supports the planning and design of a clinical trial protocol including protocol amendments. Further, the submission data tabulation model (SDTM)—trial design model (TDM) datasets are used as a source of elements for PRM. 			

As this approach to protocol authoring takes effect, the protocol repository becomes richer in content and further drives speed of authoring protocols.  This approach results in reduced overall time to approve studies/protocols based on: 			

Minimizing document hold-ups with different authoring groups. 

Using a component library that brings speed to content creation by reusing elements and also developing standard components that do not change across protocols.

Enhancing support for regional/local/country specific protocol changes by targeting specific protocol components that are impacted due to regional regulatory needs, which also speeds up overall approval times compared to traditional approaches. 

The implementation of this part of the proposed architecture can be based on configuration of pre-existing structured/component authoring solutions that meets this proposed approach.

  manages the design and build of the eCRF pages including the underlying clinical database that support these eCRF pages, all during the study build phase. This architecture component provides this feature and also includes the eCRF design tool that enables the layout and creation of eCRF pages. The study definition interchange provides a standard-based CDISC integration layer that describes the protocol structure defined during the study design via a map. This map links pre-existing elements across protocol and eCRF page elements. During the study build phase (i.e., eCRF build) the EDC platform processes the map information to link each of all protocol component elements to its corresponding eCRF page elements based on these maps. The eCRF pages are then generated including the database to store eCRF results. Within this component as eCRF pages are generated, for those protocol components for which eCRF page elements do not still exist in the eCRF library, new eCRF pages including maps will be created and maintained.  

This is the core component of the proposed architecture and functions as the connectivity layer between protocol authoring (study design) and eCRF build (study build). The study definition interchange component manages all mapping and any transformations that are necessary between protocol elements and eCRF page elements. It provides integration services that are based on CDISC standards linking protocol authoring platform to the EDC platform. The rules, transformations, and maps linking study/protocols to eCRF pages are also stored within this component.  Maintaining all these elements requires a simple user-interface to create, update, and manage components throughout the lifecycle. On the study design (protocol authoring) side, all elements in the protocol repository are exposed in the form of PRM elements within the study definition interchange layer in order to be transformed into specific eCRF page elements based on pre-existing protocol maps and transformation rules. On the study build (eCRF page creation) side, the study definition interchange component takes each protocol component exposed as PRM components and maps it to eCRF page elements based on clinical data acquisition standards harmonization (CDASH) standard, a subset of CDISC.   

Since the study definition Interchange component of the proposed solution architecture has to be designed and built, below are some key design considerations for this component: 					

Store all study definition metadata in this component.

Leverage dictionaries and CDISC standards to provide interoperability between clinical systems across study design and build (e.g., WHO Drug, PRM/SDTM/TDM/ODM/CDASH, etc.).

Align on standards naming/metadata across all areas (global, therapeutic area, study, etc.).

Maintain version control, data traceability, and audit trails for regulatory compliance.

Leverage an ETL engine that supports transformation and store maps for study metadata across standard libraries. 

The study definition interchange is a new component that does not exist in the market and will need to be developed or extended based on some pre-existing solutions.  

For the clinical trial design automation approach to be effective it is integral for the maintenance of both the standard libraries—protocol and eCRF—both of which manage and store protocol components across all clinical trials (Figure 3).  

Key groups for proposed process are described in detail below: 					

The governance committee is responsible for managing and approving overall content within study standard libraries: protocol and eCRF. They also approve QSD (quality system documents) that describe the process and policies to help manage study standard libraries.

The standard libraries librarian helps manage, track and get documentation ready to governance committees for approval. Based on approval status help notify users of standard libraries in terms of components that are ready to be published and made available for clinical studies within the organization.

The component proposer group is primary authors of components that exist in the standard libraries. This group is responsible for preparing documentation on new components including updates to pre-existing library components. Works with the librarian group in getting documentation ready for approvals via the governance committee.

These three groups in concert with the proposed process help maintain the study standard libraries and enable the proposed approach in driving efficiencies into study design and study build process. 

Benefits of clinical trial design automation

 The benefits for the proposed clinical trial design automation approach are as follows:

Structured protocol authoring drives: quality, efficiency,search, and collaborations.

Standards based development enables upstream anddownstream integrations.

Ensures compliance with SOPs and regulations.

Study design—clinical data capture build (eCRF):

Standardized protocol and eCRF libraries improve reusability,visibility, and maintenance.

Industry standards (CDISC) based metadata and datacapture.

Enhances management of eCRF while enabling enhanceddata collection methods.

Streamlined clinical development process, harmony betweenclinical operation and data management.

Facilitates easier management of documents based on documentrepository with version controlled check-in checkoutcapability, approval workflow, and electronic signatures.

Improved productivity (notifications and task management)and compliance.

Data is exchanged electronically using the CDISC-basedXML engine instead of documents.

A single authoritative source of truth is maintained andconsumed by the protocol documents and trial specificeCRF pages.

Enabling data mining/analytics around clinical trial design.

Feature Article

Incorporating CDISC-based libraries to store study components for study design and building eCRF pages.

Clinical Trial Design Automation

The International Society for Pharmaceutical Engineers (ISPE) examined issues involving supply and production of investigational medical products.at its  annual meeting in November.  

) on patient experiences with clinical trial materials examines how upstream decisions on the packaging and labeling of clinical supplies can influence the success of a clinical study. Clinical supplies that are easy to use, have clear labeling and directions can improve patient satisfaction with participating in a study and enhance compliance, according to responses from 1,400 study participants. Also, there's strong interest in direct-to-patient refill and resupply options, especially when clinic visits are difficult.  

One concern, noted Ken Getz, Director of the Center for Information and Study on Clinical Research Participation, which conducted the study for ISPE, is that a strong minority of patients say they keep unused clinical trial medicines for later use. Analysts cited the need for clearer policies and instructions on unused medicines, for investigators and patients.  

Clinical supply delivery also is important for direct-to-patient studies, which have gained more attention as an option for remote trials. While such studies may reduce burdens on clinical sites, they raise logistical challenges for sponsors in maintaining blinding, scheduling timely delivery of test products, and ensuring that patients understand directions.  

ISPE members noted tensions within pharmaceutical companies about providing comparators to other firms, particularly for newly approved therapies. More streamlined drug manufacturing systems that reduce excess production have tightened up supplies available for comparators, driving up prices. This has created "a perfect storm for counterfeits" to enter the clinical supply system and compromise patient safety, observed Terry Walsh of GlaxoSmithKline. 

Walsh and others have established the Clinical Trial Comparator Network under the TransCelerate BioPharma initiative to support reliable and efficient distribution of comparator drugs to clinical sites. The aim is to replace two-company comparator supply arrangements, which can take months to negotiate, with a network that adopts standard legal agreements for participating manufacturers to supply other network members with products needed for legitimate research purposes.  Price negotiation will be left to individual companies. 

News

Ease of use, and clear directions and labeling can improve patient satisfaction with participating in a study and enhance compliance, says new ISPE survey.

Clinical Supply Issues Challenge Sponsors and Patients

The Tufts Center for the Study of Drug Development (Tufts CSDD) recently analyzed the reasons for clinical failures for 410 drugs that entered human testing between 2000 and 2009. 

The results of this analysis show that commercial viability—as opposed to safety—is the leading cause of Phase I failures. Commercial viability played a diminishing role in the reasons for drugs failing in later clinical phases. Safety issues accounted for one-third of all drugs that failed in Phase I and Phase III studies; and for 17% of all Phase II failures.  

Efficacy issues dominated both Phase II and III accounting for more than half of the total drugs that failed (54% and 52% respectively). Tufts CSDD researchers conclude that the ever-changing commercial landscape combined with insights gleaned from later-stage studies conducted among larger patient populations present ongoing drug development risk-dynamics that are difficult for sponsors to anticipate and manage.  

—Tufts Center for the Study of Drug Development, 

Data Anlaysis

Reasons for Clinical Failures by Phase

Act Cover

I recently acquired one of those neat new fitness bands that keeps track of my daily activity and sleep patterns, warning me when I haven't run far enough this week and praising me when I have. One of the newer versions also tracks my food and drink intake, will buzz me when I'm spending too much time as a couch potato, and even keeps track of my mood (grumpy meter alert).  It doesn't directly link with my GPS watch and heart rate monitor—yet—but I'm sure the upgrade's coming for a nominal additional cost. All this real-time data about me is safely (allegedly) stored in the cloud where I can view it on my phone, tablet, or laptop. 

My neighbor across the street has recently wired his house (the "connected home") with learning thermostats programmable by phone, and with smoke detectors that can send alerts—either for smoke or when its batteries need replacing, instead of that infernal beeping. He may next buy one of those refrigerators that can notify Peapod when you're running out of milk. 

recently described the Motorola pill that is swallowed and emits a password that can be read by a computer. This is not sci-fi­—an ABI Research study estimates that 10 billion wireless devices are already connecting to the Internet today—with many more to come. Many commonly refer to this as the "Internet of things," a term used to describe the wired world where our devices track and monitor themselves, keep us informed, and cry for help when they need replacing, refilling or repairing.  

Some 15 years ago, I wrote a paper in the 

 titled "The Elegant Machine," which discussed how to introduce the concept of elegance into what had become a very busy, overly-complex, and ridiculously inefficient clinical data management process. The guiding principles of my machine—plan before you do, standardize data, push data capture upstream using best fit tools, provide online access to information, and let technology drive the process—are surprisingly still relevant, and, in a broad sense, not incompatible with the Internet of things. But, alas, many of the shortcomings of our research processes I criticized then are sadly still with us.  

In 1998, mobile telephones were clunky and far from ubiquitous. Data connectivity was primarily by telephone modem. Fifteen years later, smartphones can be found in the farthest corners of the world, and everyone is connected through the Internet. Yet, in clinical research, we're still generating queries, overcompensating with monitoring and documentation, and manipulating and transforming data over and over again as we move it through the research loop.  

Our research machine is much closer to Rube Goldberg than elegance. For you youngsters who haven't heard of Rube Goldberg cartoons, try Wikipedia. Webster's dictionary describes Rube Goldberg as an adjective for "accomplishing something simple through complex means." Yep, that sounds like exactly what we do with many of our research processes, though hardly with the amusing creativity of a Rube Goldberg machine. 

Now, like others my age, I regularly look for opportunities to simplify my life. I steer clear of garage and estate sales, try to avoid paper and ruthlessly purge my e-mail inbox. I even try to spend time now and then digging through drawers, closets, and garages to fill a trash bag or two. While I'm not quite so thrifty about my wine collection, I at least try to avoid creating new collections of other things I'll eventually have to shed. 

But in the world of research, we embrace clutter. SOPs enforce complex documentation requirements with red tape workflows, measured in volume rather than quality and necessity. Take our approach to computer system validation. Processes around validation are typically medieval—analysts and testers generate reams of printed paper with wet signatures, and paper clipped attachments of screenshots and reports. This mountain of detailed documentation is meticulously scrutinized by the regulatory and quality assurance police—painstakingly combing for non-conforming corrections or missing dates on every trivial typo.  If the documentation trail can't be measured in feet, it's generally assumed to be inadequate.  

And what exactly does this accomplish? The basic premise of validation—documented evidence that a computer system meets requirements—is inherently simple. We simply need to describe our key needs, and provide just enough evidence that the system we used has been shown to meet them. The rest of the mess is created by us. Surely we would all prosper if we simplified—describing the most crucial functions in plain, simple terms, and providing spare, clear evidence that we actually tried the functions, maybe by using the tracking tools that computer systems already offer. Some overworked auditors might actually thank us for making the review so much easier. 

The ingrained habits of excessive validation expectations—a practice that's ironically sustained by extending job security for both IT staff and auditors—is further encumbered by the timeworn tradition of sponsors conducting technology vendor audits of that validation. For some reason, each company feels it has to audit each technology vendor separately in person, sifting through those documentation haystacks over and over again. The process is often punitive—there's a small cottage industry of contract auditors for hire who feel they can only earn their pay by finding deficiencies that are often trivial or irrelevant and demanding immediate corrective action.  

This costly, time consuming, and unnecessary practice still comes in an age where different pharmaceutical sponsors are working together to solve other common pre-competitive problems in partnerships like TransCelerate Biopharma and the Innovative Medicines Initiative. TransCelerate Biopharma, in addition to helping define therapeutic area data standards with CFAST, is already supporting multiple projects to share information about the qualification of sites.  

It's not a stretch to set up a similar industry initiative to subscribe to an independent registry of audit information about other suppliers, such as technology vendors, CROs, and labs. We simplify when we do something once, and use it many times.  

You can't really blame the regulators anymore either, even though perceived regulatory risk inhibits so many companies from trying anything even remotely different. FDA has opened the door to improved efficiency with guidance documents endorsing risk-based monitoring and use of electronic source documents. And regulators are working more closely with industry in many cases to address many of our long-standing problems. Some long-held sacred cow beliefs—such as the impression that CRAs had to review every data point on-site—are not really prescribed in the predicate rules. Much of the bureaucracy of research has just evolved over time and become firmly embedded in our culture. 

Elsewhere, global demand for increased data transparency is making research data more available, yet its usefulness is still severely handicapped. It's not just that published data often do not conform to public industry standards, which makes it difficult to fully understand, much less roll up and compare data from study to study. In many cases, the published data lack sufficient context to allow thorough understanding—being able to view the data through the lens of the study protocol and analysis plan. Use of a standardized, structured protocol definition—which should accompany each posting of study data—would be an enormous leap forward.  

But just making computer-readable protocol documents available would help as well. In the same way that Google Images indexes graphics found on the web with keywords—by looking at the textual content on the page the image was found, as well as the page title, filename, etc.—we already have technology available that would allow us to extract much useful contextual information about protocols that provide useful metadata to associate with these postings of data for shared use by the research community. Instead of waiting for an order to dig back and unearth such artifacts later, the industry can simplify by just making such behavior a habit for every study. 

Which brings us back to the Internet of things. We should be using direct monitoring devices on study subjects already. We already have bottles that can track when pills have been dispensed. Companies are developing lab on a chip devices that can be used directly by patients and report back to a database. Not to mention microscopic streaming cameras that can be swallowed and stream video as with the Motorola password pill.  

But we're never going to be able to use the new technologies of everyday life in research with our feet shod in the cement of antiquated processes. So, time to get back to basics. We need to focus on the core elements of the predicate rules, such as ensuring patient safety, maintaining good science, and ensuring traceability and reproducibility of results.  

Of course, people say it's too risky, too difficult to take the first step, and too overwhelming a problem to address anyway. Which brings up the familiar anecdote of the little boy, painstakingly tossing beached starfish one by one back into the sea, who is warned that with so many thousands in the sand he can't possibly make a difference. "Well," he says tossing another, "I made a difference to that one." 

Maybe some of us can make a difference on the next study we start.  Simplifying our lives in research can make a huge difference in providing better treatments and cures to patients, even if they only happen one at a time. 

 is Chief Technology Officer for the Clinical Data Interchange Standards Consortium (CDISC). He resides near Chicago, IL, and can be reached at 

CTI Insights

Clinical research processes need to be simplified before new technology can be properly utilized.

Clearing the Way for the Internet of Things

Clinical research professionals, such as coordinators and administrators, play a key role in the success of clinical research projects. In order to meet global standards, clinical research professionals conducting clinical research involving human subjects are required to take training in guidelines for good clinical practice (GCP), which describes the responsibilities and expectations of all participants in the conduct of clinical trials, including investigators, monitors, sponsors, research ethics boards, and clinical research staff.

  Another standard which is being accepted increasingly by organizations conducting clinical research involving human subjects is training in the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS).

Clinical research training practices vary across the globe and likely rely on available resources to provide such training. Most of the clinical research training offered in GCP and the TCPS is offered through classroom or online tutorials. These formats provide the required subject matter, a quiz, and a certificate of completion as formal recognition that the training has been completed. However, this format for training often lacks the practical aspects of transferring this newly acquired information into practice.   

Frequently, training of new clinical research professionals is left to the principal investigator, who is ultimately responsible for ensuring compliance of the project with the applicable regulations. In many situations, clinical research training may be delegated to other members of the research team, or left up to the individual themselves. Inconsistent work practices, questionable data quality, and protocol execution issues may be encountered if learning the day-to-day operations of clinical research is done informally and/or on the job.

Peer-to-peer mentoring can be described as a form of mentorship that takes place between a person who has an expertise in a particular skill and a person who wants to learn that skill, where both the mentor and mentee may be at the same level in an organization.

  Peer mentoring can offer a valuable source of support and information to less seasoned staff that work within similar work environments, and can offer an organization or research team a low-cost method of training new research staff.

In response to the need for clinical research mentoring within an environment of limited resources, the Network of Networks (N2)

  developed a peer-to-peer mentoring program to provide mentoring opportunities to research professionals across Canada. By developing a system where seasoned clinical research mentors are paired with less seasoned mentees, the goal was to offer guidance to clinical research staff who have little formal training, as well as support staff in the acquisition of new practice skills.  

The N2 Mentoring Program is coordinated by a committee of voluntary research professionals, which is responsible for communication about the program to N2 members, reviewing applications, pairing mentors with mentees, and evaluation of the program. Mentors participate on a voluntary basis and the program is available to all N2 members at no cost.  

N2 is a not-for-profit collaboration of healthcare organizations and other stakeholders, in Canada, that conduct clinical research involving human subjects. N2 is a national initiative that aims to enhance Canada's research capability and capacity, whose membership includes over 200 clinical research sites across Canada.   

Development of the peer-to-peer mentoring program 

The overall goal of the N2 Mentoring Program is to pair mentors, who have expertise in conducting clinical research, with mentees, who are in need of developing new skills in conducting clinical research. As part of the planning process, the N2 community was consulted through surveys, for suggestions on topics such as mentor criteria, determining the length of the mentor and mentee relationship, and mentoring formats. By having the mentoring program under the auspices of the N2, all mentors had access to the most up-to-date research tools, standard operating procedures, information about best practices in clinical research, and access to more formal training in the regulatory requirements of conducting clinical research. The goals of the mentoring program are:  					

To facilitate a national, institutional mentoring program by pairing volunteer mentors with more junior colleagues for a four month period 

To develop a roster of mentors along with their areas of expertise 

To develop a process by which mentees will be paired with appropriate mentors 

To obtain feedback from both the mentor and mentee about their experience. 

The mentoring formats are decided upon by the mentor and mentee and can be person-to-person, via telephone, e-mentoring, or a combination of all three. 

Both mentor and mentee participants are required to complete an application form before they are considered for pairing. The form asks for demographic and contact information, area of research expertise, therapeutic area, and number of years of experience in research. Mentor applicants are asked to check a list of areas of expertise in which they can provide mentoring. Mentors are chosen based on the following criteria:  					

Research professionals who have at least five years experience in clinical research 

An expertise in a particular area of clinical research 

Interested and available to provide mentoring to less seasoned clinical research staff 

Mentee applicants are asked to check a list of areas in which they would like to receive mentoring. All participants are asked to provide consent to have their name and contact information shared once a potential match is found. 

The mentoring committee reviews all applications within five days and a response to applicants indicating their application has been received is sent. The information in the application forms is inputted into an Excel database, which is stored on a secure network. This information is the source for the mentor and mentee pairing and makes up the mentor roster for future pairings.   

When an application form is received from a mentee, a member of the committee reviews the areas in which they want to receive mentoring. The mentor roster is then reviewed for a mentor who has an expertise in the area of expertise being requested. The mentor is then contacted to determine their availability for mentoring. If a suitable pairing can be made, the mentor and mentee are contacted by a member of the mentoring committee and their contact information is exchanged.  

The mentoring committee recommended a period of three-to-four months for the mentoring relationship, with the belief that having a clear endpoint would make the mentor/mentee pair more productive. Mentors and mentees are invited to contact the committee at any point in the relationship to request assistance or another match as needed. At the three-month mark the committee makes a point of checking in with the pair to see how the mentoring relationship is progressing. The committee contacts both the mentor and mentee to obtain feedback through an anonymous online survey once it is determined that the pair has reached their goal.   

In August 2011, information about the N2 mentoring program was sent electronically to all research organizations that are members of N2. Each organization has a N2 member representative responsible for distributing research information in accordance with its own organizational process or guidelines. Interested individuals were encouraged to complete the mentor and/or mentee application forms and send them to the N2 mentoring committee. 

Six months after the initial communication, a newsletter was sent through the same process to all N2 members with an update regarding the mentoring program. The newsletter provided a description of the mentoring program and progress to date. Interested individuals were encouraged to forward completed application forms to the mentoring committee. 

On an annual basis, the N2 community provides input on the need to continue with the N2 mentoring program. In 2012, the N2 community indicated that the need for a clinical research mentoring program continued to exist.  

Through an anonymous survey, participants of the N2 mentoring program also provide input on their experiences and are offered the opportunity to provide input on how the N2 mentoring program can be improved. In the paragraphs to follow, we offer results of our N2 mentoring program evaluation. 

Currently the mentoring program has 14 research professionals who have volunteered to be mentors. Mentor applications were received from Alberta, British Columbia, and Ontario.   All mentors have at least five years of experience (range five to 25 years). The mentors come from a variety of clinical areas, such as: acquired brain injury, cardiovascular, hematology, mental health, oncology, pediatrics, and eye research. Many mentors have expertise in monitoring, auditing, training, clinical trial coordination, budget, and contract negotiation. The mentors used a checklist on the application form to indicate the areas in which they were comfortable in providing mentoring. The most common areas of expertise were consenting research subjects, clinical trial applications, education and career development, and SOP development. 

Currently the mentoring program has 14 research professionals who have requested mentoring in particular areas of clinical research. Mentee applications were received from British Columbia, Ontario, and Saskatchewan. Mentees have varying years of experience ranging from less than one year to 16 years. The mentees come from a variety of clinical backgrounds such as brain injury, cardiovascular, eye research, kidney disease, and orthopedics. Many mentees have roles in clinical research coordination, or research administration and management. The mentees used a checklist on the application form in order to identify areas in which they wanted mentoring. The most common areas were grant preparation and regulatory requirements. 

All individuals who sent applications for the mentoring program received an acknowledgement e-mail within 10 days of receiving their application. If a pairing was suitable, contact information was provided to both mentor and mentee. It was up to the mentor and mentee to make the connection and establish the goals of their relationship, the most suitable method of communication, and to determine the length of the mentor/mentee relationship. Whereas no timelines were set for the relationship, a committee member contacted the pair after three months to enquire about progress. 

As of August 2012, the mentoring program successfully paired nine mentors with mentees. In seven out of nine cases, the mentors and mentees worked in different cities. There were five mentees that had not yet been paired. One reason was that a mentor was not available to provide mentoring in the expertise being requested. In these cases the mentees were notified of the situation, and told they would be contacted once a mentor became available.   

The goals of most mentor/mentee pairings had been achieved by three months. A survey link was sent via e-mail to the 18 participants, both mentors and mentees that had completed the mentoring program. Seven participants responded to the survey, which gave a response rate of 39%. Four of the respondents were mentees and three were mentors. The mentoring committee reviewed the feedback provided by the respondents. 

The survey asked participants the following four questions: 					

Please share the best part of your experience. 

Overall how valuable did you find your mentoring experience? 

What suggestions do you have about how we could improve the program?

Do you agree to us sharing your name and best part of your experience in the N2 newsletter? 

To the final question, all respondents agreed to having the best part of their experience shared in the N2 newsletter. However some did not want to have their name identified.   Some common responses that emerged from the mentees were:  					

An appreciation of the time their mentor spent with them

The mentoring program was easy to accommodate into their busy schedule

Mentors were able to provide support through shared experience

Mentors provided valuable tools and information which helped in developing skills 

Common responses from the mentors included: 

Clinical research organizations should look to peer-to-peer mentoring for professional development.

Developing a Successful Peer-to-Peer Mentoring Program

From ePRO, to eCRFs, eTMFs, trial management in the form of CTMS, to sophisticated analytics for forecasting, modeling and trending everything from site feasibility to recruitment and budgets...there are not many areas of clinical trials that technology does not touch. But technology brings with it its own set of complications, especially in our current world of outsourcing where sponsors and CROs share data to leverage decision-making and benchmarking.  

 and our conference company CBI, producers of ClinTech 2014, surveyed where our audiences are in regard to clinical technologies. We focused on how purchasing decisions are made; integration and maintenance issues; and views of technology providers.  

The short history of clinical technologies is that it took EDC approximately 10 years to reach a 70% adoption rate. Even now, EDC may not be the primary data collection source, many trials still use paper—more likely in emerging regions, small trials, and Phase I trials. In the early adoption years, technology providers began adding on those aforementioned "e" technologies, or eClinical, that added to the chain of software services for the clinical research enterprise. Along the way, it became clear that suites from one company weren't as important to industry as best of breed solutions, which led to integration issues coming to the fore. 

But also in that time frame, there has been one significant change in the landscape that impacts technology choices—cloud-based solutions or cloud computing. At last year's ClinTech 2013, it was clear that the cloud was the inevitable choice for sponsors making technology decisions, but there was much trepidation in that choice. What about security? What about legacy data? What would the cloud look like in five years?   

We asked survey respondents to describe their feelings about cloud-based solutions (Figure 1). Thirty-four percent believe the cloud is a cost-effective solution. But a slightly greater number also find the cloud confusing or not secure.  

, written by Rick Morrison, founder of a cloud-based analytics and data collaboration company, appeared on our blog. It provides a simple and understandable outline of the benefits of cloud computing—these include:  					

 wrote about the cloud two years ago, which can be accessed here 

. Two years later, Kubick observes, "As we approach the end of 2013 the external world in general is certainly flying into the cloud, but much of the world of regulated clinical research is still frequently chained to the ground." He believes that the majority of us access and use cloud applications everyday on smartphones and pads, but there still exists a level of risk aversion, and adherence to legacy regulatory and IT attitudes and that hold industry back. "While these constraints persist within these enterprises, we're seeing the cloud as the platform of choice for collaborative initiatives such as IMI (with its eTRKS translational medicine system) and TransCelerate Biopharma and others. Smaller companies are more likely to make the transition sooner for their internal systems. And there are a number of technology start-ups gambling that the cloud will be the only platform of choice before long. Though old habits die hard, I do foresee the balance tipping within the next three years—it will simply be too difficult to ignore." 

And a note on security, both Kubick and Morrison believe that cloud suppliers are more capable of preserving security. Kubick notes that security is absolutely fundamental to their survival and Morrison says they have more experience with computer infrastructure than sponsors, and by virtue of their working with more systems and data, they become security experts more easily than sponsors.  

Diving deeper into the cloud, we wanted to look at the profile of those 5% who responded "I Love the Cloud." If you love the cloud, you are 66% more likely to be buying workflow management or document management solution in the next two years. And you are evenly distributed between a purchasing a solution to help with risk-based monitoring, recruitment or study start up at 22.2%. If you love the cloud, cost is very important to you, and ease of integration with existing solutions, potential solutions, and external providers is very important. And your primary resource for finding new solutions is Google search at 40%. 

There are varying thoughts on how clinical technologies vendors can impact the industry. In this column from early this year, 

, Ken Getz reflected on how CROs could be moving the industry forward in innovation and efficiency. From a technological standpoint, he noted, "Leading CROs are aggressively pursuing new and innovative initiatives to facilitate sustainably higher levels of speed and efficiency. They have introduced a number of eClinical solutions designed to simplify and optimize data and project management and to coordinate disparate technologies." Perceptive Informatic's (Parexel) launch of the MyTRIALS platform and ICON's launch of ICONIK are two such examples. 

Other initiatives Getz described use technology solutions to optimize investigative site performance include Covance's Xcellerate methodology and ICON's Firecrest Clinical.  

, published in April of this year, Graham Bunn, PhD, Vice President, Partnerships at Perceptive Informatics, takes the position that as sponsor and CRO partnerships increase and sponsors leave more of the management of trials to their outsourced partners, they should also leave the technology decisions to the CROs. By giving up the requirements for multiple technologies, CROs can gain their own efficiencies in the process. "This change in approach by sponsors has changed the way technology vendors work with their CRO customers. Some large technology vendors have developed a CRO partner program to better serve this segment of the industry, and in the process provided benefits to both the CRO as well as the sponsor. Vendors have implemented strictly controlled, high quality training and testing programs along with user testing (certification), company accreditation and associated branding to recognize high quality CRO partners who are familiar with their technology. This not only enables the CRO to differentiate themselves in the marketplace, but also allows sponsors to feel confident that their strategic CRO partner is correctly qualified and supported throughout the contract duration." 

In our survey, 35.8% of the respondents work for a biopharmaceutical company and 20.3% CROs (Figure 2). We asked: "What is your current model with external partners?" (Figure 3) the majority of the respondents said "plug and play by capabilities/functions with multiple providers." This was followed by vendor collaboration to develop a single solution; and a close tie between sole CRO provides an eClinical suite to meet your needs and sole CRO provider, using a data integration platform to utilize any software vendor. 

The second choice refers to reports that pharma companies are asking different vendors to collaborate with each other to come up with one solution that meets their needs. In that way, the pharma company doesn't end up using both services that don't completely meet all their needs or they end up paying for portions that they don't want or need.  

When choosing a technology solutions provider, what criteria was most important? Responsiveness to business needs and cost were closely rated as Very Important by our respondents at 69.4% and 63.8% respectively. Reputation in the market was rated Important by 48.9% of the majority. 

How respondents discover new solutions is mostly through colleagues and word of mouth, at 34.9% (Figure 4). But the criteria for choosing the vendor—not the solution—is more closely aligned. Respondents list cost, ease of use and ease of integration with existing solutions as very important, all hovering around 60% (respondents were allowed to choose three criteria). Under Important, best of breed solutions won out, followed by ease of integration for potential solutions. A word or two about integration. In our survey, 39% of the respondents noted that technology integration was their biggest challenge (Figure 5). At two recent CBI conferences, integration issues did come into discussion. And not that there is an "integration" backlash, however, some caution that not every solution need be integrated. Much like metrics, thought around what truly will add value by being integrated should be assessed. In addition, even if, for example, a CRO and sponsor enter into a partnership, which will inadvertently call for some level of data sharing, just because two entities may use the same vendor solution doesn't ensure an easier integration. Johann Proeve, Head Global Data Management at Bayer Healthcare, discussed its data management partnership with Covance at CBI's Sponsor and CRO Business Process Systems and Integration conference. He noted that even though both companies use Medidata's Rave as their EDC, these systems are highly configurable—and customized to their needs—so integration is not necessarily a seamless activity.

And there are other challenges to integration or solutions unification, which came up during a webinar about Medidata's IRT and EDC solution (Figure 6). These challenges resonate with Kubick's overall cloud challenges above. 

But it is true that the respondents to our survey think that integration is important—either with existing solutions, potential future solutions or with their external providers. 

Our respondents said top areas they are planning to purchase solutions in the next two years are risk-based monitoring, workflow management/document management, and study start up. For trends, respondents rate mobile technologies as the only "must-have" technology—other choices were big data, EHR integration, investigator portals and clinical trial supply management.  

If we are to agree with Wayne Kubick, that the tipping point into cloud computing is only three years away, then more and more companies will need information on these technologies. 

 will be the lead media partner on CBI's ClinTech 2014 conference, which will address these topics, and we will continue to feature articles, news and more about clinical technologies in our ClinTech section on our website at 

www.appliedclinicaltrialsonline.com/ClinTech/

Survey

As we move towards cloud-based technologies, lingering questions and concerns remain.

Clinical Technologies

	The EMA is currently reviewing and analyzing more than 1,000 comments received during the public consultation on its draft policy on trial data, which ran from June to end of September 2013. The Agency has warned that the need to study so many submissions may delay the issuing of a final policy, which was initially planned for the end of 2013.

	"The public consultation on the policy has generated input from an unprecedented range of stakeholders. Patients, healthcare professionals, pharmaceutical industry representatives, researchers, transparency campaigners, academic and public institutions, health technology assessment bodies, and a range of others sent their comments to the Agency," noted a statement released on November 13. "Many of the contributors provided detailed in-depth comments, some of them substantial, some of them technical, including suggestions relating to methodological and technical aspects of the implementation of the policy."

	As part of its collaborative approach to developing a methodology for the release of clinical trial data with its stakeholders, the Agency is currently devoting attention to all comments received and reaffirms its commitment to transparency and the principles of publication and access to clinical trial data, EMA added. To conduct the appropriate in-depth analysis required, the Agency will spend additional time in this reviewing phase.

	"The Agency has embarked on the development of a policy on publication and access to clinical trial data because it believes that the release of data is about establishing trust and confidence in the system," continued the statement. "The Agency is also firmly of the opinion that availability of data broadens the scientific knowledge base, fosters innovation, and encourages investment in the development of medicines, and ultimately benefits public health."

The EMA announced the possibility of a delay of their much-awaited guidance on trial data due to the unprecedented response received during public consultation.

Jury's Still Out on How Best to Handle Trial Data

In various internal and external surveys this year, 

 has evaluated its print magazine, digital products, and web site to determine what our readers want and how they are consuming information.  

Digital product adoption among our readers is growing at a faster rate than what we would normally anticipate. That includes our eBooks, use of the magazine's digital edition, webinar attendance, and web site access for news and articles. 

 To address these needs, in 2014 we will be offering six print issues of 

, down from the 10 issues we published in 2013. In no way will this affect the authoritative quality of our content. We will continue to accept and publish the peer-review articles that we are known for, which are externally reviewed by our experts on the editorial advisory board. These articles will appear online first and will be identified as peer-reviewed. 

The six printed issues will be highly-targeted and focused on those areas that our audience have rated highly over the past two years. These are: global trials; clinical technologies (ClinTech); oncology drug development; clinical trial management; clinical trial innovations; and drug safety and testing.  

 is in conferences. In a recent Industry Standard Research survey, it showed in the next 12 months conferences would be a major source of information. Because of our relationship with CBI, a producer of clinical trials-related conferences in the United States, we will increase our involvement in the 2014 roster of CBI clinical conferences.  

Additionally, we are increasing our coverage and frequency of online information. We are fortunate to have over 140,000 dedicated and loyal professionals worldwide as readers of 

Applied Clinical Trials is pleased to announce exciting changes to the way we offer content to our readers.

Applied Clinical Trials-12-01-2013

On Trial—Europe's Response to Antibiotic Research Gap

Clinical Trial Design Automation

Clinical Supply Issues Challenge Sponsors and Patients

Reasons for Clinical Failures by Phase

Act Cover

Clearing the Way for the Internet of Things

Developing a Successful Peer-to-Peer Mentoring Program

Clinical Technologies

Jury's Still Out on How Best to Handle Trial Data

Exciting Changes for Applied Clinical Trials in 2014

Training and Education

Virtual CRA Meetings: Promoting Discussion, not Silence

Events Calendar

Applied Clinical Trials Digital Edition - December 2013/January 2014