Sheila Rocchio

Data has truly become the currency in our everyday lives, and the volume and speed at which it is being collected, processed and exchanged is staggering. For instance, every minute, 188 million emails are sent, 4.49 million Google searches are conducted, and 4.5 million videos are watched on YouTube.

 This proliferation of information can also be seen in the world of clinical research, where the amount of clinical data per trial has increased by 183% in the last decade.

The growing volume of clinical data illustrates one significant way in which the drug development landscape is evolving. As clinical trials are becoming more decentralized, the variety of data types and sources, including genomics, biomarkers, wearables and images, that are being used in drug development is also expanding. With the amount of diverse data that must now be collected and analyzed, the life sciences industry is faced with increasingly complex studies that present new challenges in clinical data management.

From October 4 to December 30, 2019, eClinical Solutions and the Tufts Center for the Study of Drug Development (Tufts CSDD) conducted a survey to understand the trends in clinical data management and assess how sponsors are responding to current challenges. 149 individuals in senior-level data management, data sciences, biostatistics, information technology and clinical research operations roles participated in the study. Of the respondents, 48% were one of several individuals within an organization responsible for clinical data, 33% were primarily responsible for clinical data and 19% were frequent users of clinical data systems. 

The majority of respondents came from pharmaceutical (41%) and biopharmaceutical (37%) sponsors, though CROs (10%) and independent contracts (6%) were also represented. The sizes of respondents’ organizations varied from small sponsors (30%) that had initiated an average of 2.9 trials yearly, medium sponsors (29%) that had initiated an average of 23.8 trials yearly and large sponsors (17%) that had initiated an average of 112.4 trials yearly.

Sponsors are collecting more data types than ever. Though non-CRF data is the most commonly used in clinical trials among 87% of respondents, a variety of other data types and sources are also being used. Nearly two thirds of sponsors are incorporating direct data capture, apps, devices and medical images as other data sources, while roughly one-third are using electronic health records (43.4%) and omics data (35.5%).

Data sources contributing to significant delays

The growing number of external data sources is associated with longer database lock cycle times with more than half of the study respondents citing non-CRF data as a primary contributing factor. Since 2017, this has resulted in a 40% increase in time from Last Patient Last Visit (LPLV) to database lock. Specifically, large pharmaceutical companies using four or more sources are experiencing a three-week increase in Last Patient Last Visit (LPLV) to database lock.

Last Patient Last Visit (LPLV) to Database Lock Cycle Times

Labor intensive data management activities

Although the availability of richer data sets is essential for gaining deeper insights to advance drug development, sponsors are faced with challenges in all data management activities related to organizing and reviewing the immense volume of data. Among all participants in the Tufts-eClinical Solutions study, analyzing and consuming data was rated as the least challenging of these activities, though over fifty percent of respondents still noted this activity as somewhat or extremely difficult. Of the seven key data management tasks noted in the survey, participants highlighted the process of initiating relationships with data providers as the most time-consuming and labor intensive. This highlights the opportunity for improving vendor relationships as a crucial element in alleviating difficult data management duties.

Data management activity labor intensiveness

Unsophisticated tools to centralize and standardize data

Even though the variety and volume of data continues to evolve, making data management activities more difficult and time consuming, the tools used for data integration and analytics remain relatively unchanged. 75% of companies are still using SAS as the primary tool to convert, explore and analyze data.

With the changing landscape of clinical research presenting challenges in how companies organize and review disparate data types from a multitude of sources, all participants in the Tufts-eClinical Solutions study recognized the need to find solutions. Potential areas for improvement that were highlighted included handling more external data sources, decreasing cycle times through streamlined processes, encouraging patient-centered data acquisition strategies and developing better opportunities for real-world data uses. Life sciences organizations identified several ways in which they are responding to evolving clinical data management requirements in these specific areas.

When an organization outlines a formal data strategy to determine how data will be collected, processed and analyzed, there are clear benefits to clinical research. The greatest impact is to database lock times. Database lock is accomplished 10 days faster with sponsors that have implemented a data strategy compared to those that have not. Since large companies are managing more data sources, they are also more likely to have implemented a data strategy, especially given that 53% of organizations that are using five to six data sources experience longer times to database lock.

Though there are significant benefits, only one-third of the survey respondents have implemented a defined data strategy. Almost half of the respondents were either still examining or planning a data management initiative in the next few months. This means that there is still a great opportunity for all life sciences companies to leverage the benefits of a formal data strategy in reducing trial delays.

To keep pace with the growing number of disparate data, organizations are turning to more advanced tools. The survey findings show that clinical data hubs or repositories are being used more often than other systems, including EDC and SAS-based infrastructure. However, EDC is still being used most often for specifically integrating and organizing direct data capture. Tools like clinical data platforms with robust capabilities to help data managers import, transform and review data will become powerful assets as data sources continue to increase.

Sponsors using a data hub or lake also had more confidence in their analytics capabilities in areas associated with analytics dashboards, interactive visual exploration, the ability to publish and collaborate on analytic content, and augmented data discovery.

Integrating new technology into current systems is just one element in establishing mature analytical capabilities. The survey also revealed a strong association between these capabilities and the implementation of data strategies. Over 50% of respondents who have a defined data strategy noted that their analytical capabilities are more developed.

Another benefit to having definitive data strategies can be seen in the areas of artificial intelligence (AI) and data science competencies. Organizations that have implemented a data strategy are more mature in terms of researching or implementing AI, machine learning and deep learning capabilities. These companies are also more likely to be developing new data sciences functions or specific data sciences roles. In fact, 47.2% that have implemented a data strategy have also established a data sciences function.

Developing analytical and AI capabilities is crucial to preparing for the digital transformation that is sweeping across the drug development industry. Life sciences companies must now meet the increased demand for clinical data and real-time insights from a variety of distinct sources. By automating time-consuming and labor-intensive data tasks, sponsors are able to support greater access to and deeper insights into data to drive innovation and accelerate drug submissions and discoveries.

Respondents to the Tufts-eClinical solutions survey agreed that there are tangible benefits to laying the foundation for AI and data science through formal data strategies. 85% of all respondents rated these qualities as somewhat or very beneficial:

Increased visibility of data to stakeholders for faster decision making

Decreased cycle times through more collaboration and shared analytics

Cost-savings through resource optimization and reduced rework

Faster acquisition and benefits from new real-world data sources that contribute to development


Conclusion: a new era of clinical research

In this modern era of drug development, clinical data has become one of the most valuable assets for life sciences organizations in powering digital transformation. As the Tufts-eClinical Solutions study demonstrates, delays in clinical trials, measured through database lock cycle times and through manual efforts and time-consuming processes associated with assembling data sets for review and insights will continue to increase without the implementation of new strategies. The diversity and volume of clinical data is also growing exponentially, and the tools for managing these must improve to keep pace.

Industry leaders are recognizing that evolving their approach to the research process is critical. By adopting formal data strategies, implementing modern technologies like clinical data platforms and expanding data science competencies, analytics and AI capabilities, sponsors can gain more control over the research process and drive actionable insights from new data streams to continue to push and accelerate drug development.

Anticipating the Impact of the Patient Engagement Movement on Clinical Operations

, Presentation at CROWN conference, Slide #9, January 202

Articles

With an increasing amount of diverse data that must now be collected and analyzed, the industry is faced with increasingly complex studies that present new challenges in data management.

 Enabling Digital Transformation: Managing External Clinical Data Sources to Advance Drug Development

	Palatin Technologies is a biotech company focused on developing targeted, receptor-specific, peptide therapeutics for the treatment of diseases with significant, unmet medical needs and commercial potential. Currently Palatin is developing bremelanotide for the treatment of female sexual dysfunction (FSD), of which there currently is no approved drug on the market for FSD.

	Study 54, PT-141-54, was a large, complex Phase IIb study which looked at three different indications of FSD: female sexual arousal disorder (FSAD), hypoactive sexual desire dysfunction (HSDD), and those with a combination of both arousal disorder and desire disorder. The study comprised 397 randomized and 394 dosed (1,142 patients recruited) across 67 U.S. sites. The study’s primary endpoint was the change from baseline in the number of satisfactory sexual events experienced by patients using bremelanotide.

	Palatin chose the LogPad® System from PHT Corporation to capture all efficacy endpoints. Study 54 had eight patient reported outcomes (PROs) with multiple data points in each. The LogPad® System included a number of different assessments:

	     · A diary completed at home by patients after every sexual event

	     · A clinic-based questionnaire completed by the patient

	     · A clinic-based questionnaire completed by a clinician

	     · Distress associated with that sexual dysfunction

	     · Satisfactory sexual events (SSEs), a count from event-based questionnaire data

	Palatin collected subject reported data on each sexual encounter including a single question regarding whether the encounter was satisfactory. In-study analysis, using pre-programmed, blinded data reports, the percent of satisfactory events and the number of doses revealed if patients were dosing more as they improved, or as they increased the number of satisfactory events. Palatin also used this at-home data as a tracking mechanism toward the end of Study 54 to determine each patient’s status in the study.

	There was one LogPad® System mobile device per patient, with different logins for patients and clinicians providing clear separation between the at-home and in-clinic portions. All efficacy endpoints were based on data collected via questionnaires and the LogPad® System application required completion of all questions. This resulted in 100% completion of required information and prevented discrepancies in the data entered.

	The protocol included two time points for screening evaluation: The first was at Visit 1, and contained questionnaires completed as part of the diagnosis and initial screening assessments. The second was during the screening month between Visit 1 and Visit 2. This was a one-month period with no study drug treatment during which the diagnosis was confirmed using data collected at home following sexual activity. Using data collected at the in-clinic Visit 1 and during the at-home screening month, screening questionnaire scores and percentage satisfaction rates during the one month, at-home screening period were calculated and displayed in a summary report. Palatin used a pre-programmed color coding system in the summary report to call out numbers or values that did not meet the screening criteria.

	In an always available, episode-based eDiary report, patients recorded the time of a sexual encounter and the time of the study medication injection. There was also a reminder question which was available from 6:00 AM to 11:59 AM, prompting the patient to enter data if there was anything to report (i.e. any sexual activity). The alarms were selectable between 6:00 AM and 11:00 AM with reminders every 30 minutes. Real-time access to encounter and dosing times provided insight into both time to onset for the medication effects and study compliance. Palatin noted 64% of events recorded occurred between 8:00 PM and 12 AM and made sure the diary was available during those hours. In addition, the study drug and encounter times data were able to show that of all the encounters which occurred in the 1.75 mg and placebo dose arms in the double blind period of bremelanotide Study 54 (1,471 encounters), approximately 72% (1,054 encounters) of those occurred within 16 hours of dosing.

	Privacy of eDiaries--Data collected in FSD trials is very sensitive. Giving patients the LogPad® System to answer questionnaires provided anonymity which allowed participants to be honest in their responses. Cheryl Van Walsh of Palatin explained, “If patients had to go and sit with their doctor at every visit and talk about the number of sexual encounters and satisfaction levels and arousal, we would not have collected the same quality data. In indications in which sensitive data are collected, it’s so very important to make patients feel comfortable. An ePRO system lends itself to collecting good quality data for this type of indication.”

	Training Ensures Compliance--Ongoing, proactive eLearning and communication with sites was a key to the success of Study 54. Going onsite and to investigator meetings, and using an adaptive training strategy for site and CRA staff, had tremendous value.

	Palatin and PHT conducted ongoing training during the key enrollment period of the study, offering training sessions to all sites at a scheduled time for about seven weeks. Site staff were invited to participate as many times as they wanted. Palatin also required the CRAs to moderate these trainings, ensuring that the CRAs were following up with the sites, that they understood the training sites were receiving, and that they could effectively assist sites with any issues that occurred. Palatin spent a good portion of CRA meetings talking specifically about issues that arose during site calls to PHT on anything sites were seeing in the data or devices. Cheryl Van Walsh, former Clinical Operations Project Manage for Palatin, commented that this “level of detailed information gathering and sharing helped the team know what they were looking for and how important it was.”

	Palatin also invited PHT to include messages for sites in Palatin’s regular newsletters, such as information PHT may have learned from analyzing help desk calls from the study sites or discussing common sources of data change requests.

	Palatin used StudyWorks™, a secure, online reporting portal of all eCOA data collected by any PHT device, to create and review compliance reports by site, patient and country, along with other detailed data. Reports included diary data collected from each patient, such as [or] including screening criteria, continuation decision, date of continuation decision and the patient’s current status.

	Patient eDiary compliance was critical to study success as efficacy data was collected via the LogPad® System. As visits were monthly, Palatin did not want to wait 30 days to learn a patient was not completing her diary. It was critical for sites and CRAs to use StudyWorks™ to track patient compliance between visits and proactively monitor and manage compliance to maximize the return on investment for the ePRO System.

	Analysis of PHT operational data across numerous eCOA studies indicates sites that review StudyWorks™ frequently have higher compliance rates. Palatin trained CRAs on StudyWorks™ and encouraged them to use it to obtain real-time data and standardized reports on significant study metrics like patient compliance and enrollment. Palatin’s CRAs worked with the site staff to remind patients during a mid-month call to complete their diary. This greatly improved patient compliance and produced quality PROs.

	Van Walsh explained, “It’s critical that the site knows the sponsor is invested in the study and is looking at the data on a daily basis. When you have that level of confidence from the site that their specific activities are making a difference it boosts

	their investment in following study procedures, facilitates problem solving, and prevents loss of data. StudyWorks™ helps sites and CRAs be vigilant when reviewing data. By using StudyWorks™, SmartReports™ Compliance Reports and alerts, a site coordinator can rapidly identify patients that have not been sending data and can follow up with that patient to provide support and answer questions so they can more easily comply with the protocol.”

	During the first third of the trial, Palatin saw a high number of screen failures based on one aspect of one questionnaire: the total FSFI score, which is a global measure of sexual function. They started receiving calls from investigators reporting that these patients did, in fact, have decreased desire disorder but were being screened out because of the total FSFI score. By analyzing data made available through StudyWorks™ Palatin was able to see the issue early in the study and make the necessary revision to their inclusion and exclusion criteria, change the protocol and improve enrollment by not inadvertently screening out desire-only patients.

	Palatin had robust, consistently positive data across all the questionnaires in the Phase II study, including the primary and secondary endpoints.

	Rob Jordan, Executive Director of Clinical Operations and Project Management at Palatin, said, “Study 54 was a great example that successful trials are the result of collecting quality data utilizing solid technology and strong collaborative efforts between the sponsor and service providers.”

	   · Patient centricity is here to stay, but balancing that with clinically meaningful information is an ongoing challenge. PROs are a significant part of the focus on the patient.

	   · Electronic data capture is sophisticated and provides flexibility to collect a significant amount of quality data          very easily. ePRO provides the ability to plan an eDiary availability window around the most likely time the          event will occur. It is important to leverage ePRO to gain efficiencies in your study and capture accurate,                reliable data.

	   · eDiaries give patients privacy and anonymity. Not having to do face-to-face reporting with the sites, especially      regarding sensitive topics can result in increased data capture.

	   · Reminders such as audio alarms and on-screen messages help maximize data collection.

	   · Ongoing training is vitally important for improving site and patient compliance.

	Palatin has initiated its Phase III program for bremelanotide in pre-menopausal women with FSD.

	Van Walsh said, “We’re taking everything we learned in this trial and transferring it over into Phase III. Those things we did well we’ll try to do again. Those things that could be improved, we’ll change. But the biggest takeaway is that we have built such a good foundation and relationship with PHT through the Phase II study, we will realize efficiencies and robustness is our very important PRO data collection necessary for Phase III.”

Sheila Rocchio, MBA, Vice President of Marketing and Corporate Strategy, PHT Corporation

Palatin Technologies is a biotech company focused on developing targeted, receptor-specific, peptide therapeutics for the treatment of diseases with significant, unmet medical needs and commercial potential.

eDiary System’s Importance in a Clinical Trial for Female Sexual Dysfunction

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of novel therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation.

Celgene evaluated the safety and effectiveness of OTEZLA®, an oral inhibitor of phosphodieasterase-4 (PDE-4), in three global clinical trials involving 1,493 patients worldwide with active PsA. The FDA approved OTEZLA® in March 2014.

Celgene wanted to determine whether patients treated with OTEZLA® would show improvement in signs and symptoms of PsA, including tender and swollen joints and physical function, compared to placebo. Celgene chose to use the SitePad® System eCOA (electronic clinical outcome assessment) tablet from PHT Corporation to collect data about patient symptoms as observed by physicians through the ACR assessment which was used to assess efficacy. The eCOA tablet was used to collect quality of life data including SF-36, EQ-5D, MOS Sleep Scale, and WLQ-25. 

In addition to QOL data, the patient also recorded the HAQ-DI, a patient’s assessment of pain and a global assessment of their disease. Patients with axial disease also completed the BASDAI. Sites completed the 76/78 Joint Assessment, a physician’s global assessment of disease, a dactylitis assessment, the MASES, and the PASI for patients who had more than three percent of psoriasis. 

Over the course of 3.5 years Celgene collected 4.5 million data points. Celgene chose to use an eCOA tablet instead of paper because it enables clinicians and patients to record real time clinician and patient outcome data electronically from the start. Once entered onto the tablet the data is transmitted into PHT StudyWorks, a secure online portal of all electronic clinical outcome assessment (eCOA) data, and was available for review and report on subject compliance, safety and retention. This significantly reduced monitoring and data cleaning costs. Elisabeth Kurkimilis, Senior Study Manager at Celgene, said, “Convert that into monitoring time and expense, because once the information is directly entered into the tablet, that's your source.”  

While Celgene did have a paper backup system in place, the number of paper instances Celgene used was less than 2% across the global studies. 

Celgene collected clinician and subject outcomes. Both groups used the tablet to enter their assessments, capturing study-specific clinician and patient assessments at the investigator site.  

 – The program included patients who were “Snowbirds,” spending summer in Canada and winter in Florida. To handle this issue and transfer of a patient across sites, Celgene put an entire patient transfer document into place to make sure patient data were transferred so they could capture the additional data for Snowbird patients when they transferred. Celgene took the data from PHT and transferred it to their CRO, who performed a manipulation and delivered two datasets for Celgene’s review.  Various programming checks on the data looked for mismatches and made sure everything lined up.

Improving Patient Retention and Compliance

 – The secure online reporting and monitoring portal helped Celgene improve patient retention. When patients came in for site visits monitors could show them where their symptoms started, where they were at the moment, and the difference. If patients said they weren’t sure they were doing well the investigator could show them how they had progressed throughout the course of the study. To assess potential patient fatigue Celgene asked study coordinators and internal staff, some of whom had not seen the questionnaire before, to see how long it took them to complete it. Most people spent between 30 and 40 minutes on the complete set of patient questionnaires. To minimize impact from potential patient fatigue Celgene ordered questionnaires by importance for secondary endpoints, so the first questionnaire patients saw on the tablet was the key questionnaire Celgene needed.

An eCOA tablet handles the volume and allows your CRAs to spend more time at your sites paying attention to issues at hand.  For us that was a huge, huge saving.” 

      = $3,250,000 saved   per study X 4 studies

Total savings across the program = $13   million dollars 

As of December 31, 2013 Celgene had completed over patient 17,800 visits. There were over 166,000 expected questionnaires and assessments on the eCOA tablet: The completion rate was over 99%. For Celgene’s primary endpoint they achieved a 99.5% effective completion. “From our standpoint having that data readily available was phenomenal,” Elisabeth said. “The assessor endpoints were 98.5%. Imagine the problem trying to achieve that number on paper. You miss a questionnaire, you miss certain questions within a questionnaire, and if you lose two questions on an SF-36, you start losing pieces of domains you can analyze.”  

Celgene did not provide training eCOA tablets to CRAs at the IM, but allowed them to take them back with them after the IM.  “We provide so much information to CRAs at the IM it’s hard for them to comprehend all of it and to understand what they’re supposed to do once they get back,” Elisabeth said.  After the IM, they can sit with a physician or study coordinator and walk through how to assign a patient and how to do assessments with the trainer. 

After submitting the NDA, Celgene preplanned for their sponsor inspection, and conducted inspection readiness training for about a year before inspections occurred, so they had all documents inspectors requested. Elisabeth spent a number of hours with the inspector going through a point-for-point comparison of the source data for primary endpoints. The StudyWorks portal gave the Celgene team the confidence to know they were presenting high quality data and they could answer questions about the data throughout the trials and during their inspection quickly.  Because Celgene trained sites before they had a health authority inspection, each site was aware of how to access requested data related to any aspect of the trial. 

While preparing for inspection, Celgene had a weekly meeting with program suppliers and eventually reduced the schedule to every two weeks. It took about 30 minutes each month to discuss four studies. “Having that time built into your calendar and having the buy-in from your cross-functional team to attend those calls is vital so everybody knows what they need to do,” Elisabeth said. 

 – The best laid plans encounter pitfalls, what is important is how you react and work through problems: “Plan, plan, plan with your internal team, your partners and your vendors,” said Elisabeth. For example, it took about seven weeks to get wireless access hubs into Russia because Celgene had to go through so many lines of approval.  “Preplan with your vendor, and you’ll be ready for any obstacles,” is a key recommendation for managing a large global trial with complexity.   

 – Elisabeth recommends before you get to database lock, make sure you have a database lock plan in place. What are you going to do? What's going to be acceptable? Once you lock your database, you don't want to unlock it. It needs to be clean before you lock it.  “If you have an endpoint and a lock coming up, plan your reviews early so if you need to make updates to the system sites can make them early to allow for smooth data reconciliations.”

Casebooks are Different than eCOA Archives

 – Casebook Preparation was very important for Celgene. PHT has its own format for providing data for archives, as do other vendors. Celgene determined how to integrate all the pieces of data so when they provided their information to a health authority according to the standard, and were able to look at one patient and all their data as a whole. 

 – If you have DCFs you want to make sure they don’t mount up on you. At Celgene’s first meeting with PHT they had about 70 DCFs or site questions. They reduced the list to a manageable three or four. “Old ones fall off and new ones will come in, but that's a very manageable level as you're working into a database lock,” she said.  

Consider Data Entry Requirements Up Front

 – “The review of the specifications will carry a trial through,” Elisabeth explained. “Have this done early so if when you start getting your transfers and you see a problem you can recommend, remediate, and make changes to that transfer document to get what you need.” When it comes to reviewing data the biggest piece of advice Elisabeth has is about how often data is reviewed: “When you're doing site and patient assessments, if your site is a little quirky and doesn't tend to follow the rules, you want a lockout to make sure the data are entered within a specific visit.  We worked with PHT to build those lockouts in the system, with a generous 16-hour post visit window to complete questionnaires and assessments.”   

 – This is the one of the most important parts of a clinical trial in general and an eCOA System in particular “You want to ensure the CRAs working on your program are adequately trained so they know how to use the SitePad and what StudyWorks can do for them,” Elisabeth said. “When CRAs understand the process and how to use the SitePad, it makes it easier for the group and makes your job as sponsor/manager much easier.” Celgene allocated training time at IMs. “Think early on about what kind of training you want to do and how often you want to do it – in-person, webinar, small group training – and get your team that information.”  The training engaged coordinators: When Celgene started the program many coordinators said their physicians would never do assessments on an eCOA tablet, but would only use paper. After the first six months of the study, principal investigators asked if they could use the SitePad in their regular practices and get output from StudyWorks. 

 – Elisabeth recommends getting the eCOA tablet in as many hands as possible to see if they can break it, if people need extra training, or if they have issues with how questions are worded.  Celgene asked its team members to go all the way through physician and patient assessments. Then Celgene gave the SitePad to some of its physicians and asked them to follow the flow of the physician assessments, and report on how it worked. Getting their input told Celgene ahead of time how they might experience adoption in the field. That exercise was very beneficial because Celgene was able to make changes to make it easier for its sites to use the SitePad.

– “The sponsor and CRO need to review reports,” Elisabeth explained. “For Celgene the metric for questionnaire completion by visit report was hugely important. We stayed on track and on the same page by using StudyWorks to compare the date of the subject visit vs. when they completed their ePRO and ClinRO assessments.” 

Over   the course of 3.5 years Celgene collected 4.5 million data points.

Celgene conducted the program in 23 countries and   26 languages, with English   for primary endpoint. 

There   were 126 subject and 188 assessor questions. There were over 17,800 visits   completed. 

The   study achieved a completed questionnaire and assessment rate of 99.16%, with   166,702 expected and 166,301 completed.

Celgene   achieved a 99.5% completion rate for the primary endpoint across the program,   with 98.5% completion for assessor endpoints.

The   number of paper instances Celgene used was less than 2% across the study,   with between 1.4% and 1.6% of paper instances out of over 166,000 entries.

In this brief video Elisabeth Kurkimilis discusses the 

Elisabeth says, “Our steps for success were to plan, train, document, and remember that everybody is on the same team. And you can make mistakes as long as you don't put a patient's life in jeopardy. Learn from mistakes and make improvements. That’s key to the success of any program.”

, MBA, is Vice President of Marketing and Corporate Strategy at PHT Corporation. She can be reached at 

 is Senior Marketing Manager at PHT Corporation. She can be reached at 

Celgene Corporation uses the PHT Corporation SitePad System and StudyWorks to collect patient-driven eData for OTEZLA (apremilast) tablets approved by the FDA in March 2014

Celgene Uses PHT's eCOA System in Global Phase III Trial

	This post first appeared on our sister publication's site, 

	In late 2013 Amazon announced they are testing unmanned aircraft/drones for same day and possibly same hour package delivery to customers. These vehicles will someday have the potential to fly packages from local distribution centers providing lower costs to Amazon and increased satisfaction to customers by delivering the right product at the right time. The drones represent a very interesting and real example of Amazon building out its core value thesis of reducing the steps and layers between people and the products they want to buy which has generated billions in revenues and shareholder value over the last decade and continues to grow.

	There is a similar trend in healthcare and clinical research: finding ways to better connect patients with the medical services and therapies they need at exactly the right time. For clinical research this falls under the patient-centric moniker which is cropping up in conferences and articles and is a focus for a number of life sciences companies. Every pharmaceutical company today is patient-centric and focused on patients but what does patient-centric really mean for the healthcare ecosystem and for drug developers?

	Similar to Amazon’s mission of being “earth's most customer centric company, a place where people can come to find and discover anything they might want to buy online” there is a changing goal of drug developers to become the earth’s most patient-centric organizations discovering and making the medicines and therapies people need to stay healthy, treat disease and improve quality of life. Almost 20 years ago, Amazon was able to cut out the middleman between people and the products they want. Who is the middle man in medicine and clinical research? Is it the doctor, the pharmacy, the hospital or the payer?  How will medicine - and with it, research - change in the coming decade with the advent of big data, personalized medicine and quantification of daily life to take cost out of the current system while improving outcomes? And who will be the winners?

	I don’t know what the new models will be but I see the informed patient as the winner. Like any other customer, a patient needs a reason to “buy” – or participate in a clinical trial. They should have at the very least the same level of information, respect and sense of community similar to what is available for other types of products and services.  In many cases the choice to take a given therapy or participate in a clinical trial may be one the most important choices a person ever makes.  And yet unlike many other products, there is much less generally available information to help make that decision.  When choosing a vacation destination, a school, a doctor or even a pair of shoes a simple Google search will produce numerous reviews written by others that have experienced or purchased the same product. 

	Of course the stakes are much higher in medicine and clinical research than in the purchase of retail products, vacations or even the choice of a service provider. The outcomes are not certain. In a drug trial you may get placebo. There is no ability to “return” anything although there is the potential upside of a better outcome and/or quality of life, which is the reason most commonly cited by patients as their motivation for participating in research according to 

	With drugs there is information but gaps that companies like PatientsLikeMe are filling to determine how drugs and alternative therapies work on people with similar profiles. When searching for data on smartphone users across the world I can search a Google database with breakdowns by demographics, region, and type of data plan for 40+ countries around the world. Wouldn’t it be helpful to search similar information clinical trials being run for a given therapy?

	The data exists, but it is not made publicly available. Drug developers sensibly don’t want to reveal too much information on their billion-plus dollar research projects. They rely on a lengthy informed consent, which in describing the pros and cons of the research details the possible good and long list of bad things that could happen to patients, but of course they make no mention of alternatives. Physicians who are charged with helping patients and potential participants weigh the pros and cons of treatment options including participating in research more than likely do not have all the relevant data available to help make that decision.  

	There is an opportunity for sponsors to share a little bit more to change the incentives for patients and physicians to participate in research.  People are already finding out the information through channels like YouTube, Facebook, LinkedIn and other social media. There are patient advocates and bloggers for almost every disease who are sharing information on their own experiences including research trials within their spheres of influence. That information is finding its way to broader disease communities. With the advent of the Bring Your Own Device (BYOD) models within corporations and now in clinical research sponsors can leverage patients’ own technology and data to offer a broader set of capabilities to it easier and more convenient to fully participate in research.

	eClinical technology vendors are moving toward building patient suites for clinical trials. These are broader sets of offerings that work as standalone products to collect data and promote patient healthcare. On top of informed consent, new products can improve patient engagement, recruiting, medication monitoring, patient safety, and patient education. Sponsors can work with vendors to develop an app for every trial. Patients can download the app for visit reminders, the most recent trial news, a form to contact their site person, information sharing – whatever the sponsor can offer and patients can use. Imagine you’re a patient, you’re traveling, and you develop a symptom you’re worried about. You can click on the app and it will show you the nearest site participating in the trial.

	To those who raise the privacy issue my response is that information sharing and privacy are not always mutually exclusive. In clinical trials sponsors can’t know who individual patients are, but they can have a conversation and think about what useful information they can provide to deliver greater value to those patients participating in research as well as the broader disease community. Whatever the outcome of the program there is value in the science, and getting the message out there, whether good or bad, benefits the community at large.

	Drug research, medical care and therapies are changing.  There is a general consensus that the day of the broad blockbuster drug are coming to an end.  That may be true but there is also optimism and evidence that the industry is on the brink of a renaissance in drug development, and of finding amazing ways to treat disease on a global level for smaller populations much more effectively. What we had before in terms of efficacy and safety will look crude by comparison in 30 years.  Patient centricity is crucial to this effort. We need to find the right people, let them know they are the right people, get them into the right research with the right doctors, and put the pieces together.  Whoever figures this new world out first will be like amazon – a leader, an innovator and the generator of tremendous value.


	Sheila Rocchio, MBA, is Vice President of Marketing and Product Management at PHT Corporation, whose mobile eCOA Systems help pharmaceutical companies and CROs conduct clinical trials programs with greater confidence, ease and accuracy. She can be reached at 

There is a similar trend in healthcare and clinical research: finding ways to better connect patients with the medical services and therapies they need at exactly the right time.

Patient-Centric Clinical Research: A Renaissance in the Making

There are a number of common adages that float around the clinical trial industry, which are usually based in some form of truth: 

Access to patients is the number one problem in clinical research.

Eighty percent of patients come from 20% of sites, but sponsors keep going back to 100% of sites.

Monitoring hours are one of the highest costs in a clinical trial. 

 Laurie Jassenoff, Vice President, Palm Beach Research Center  

These phrases, while sounding cliché, do highlight some of the most frequent and cost-heavy challenges in clinical research and relate in one way or another to effective clinical trial management. But the questions remain: How do organizations proactively manage the many different moving pieces and parts of a trial? How can sponsors and CROs alike harvest and institutionalize information on how to run trials effectively? How can operational managers see useful information across dozens of trials to keep programs on track and identify potential problems before they happen?  

These are the types of problems a clinical trial management system (CTMS) can address. However, it is not always a smooth and seamless process.  

When web-based EDC and automated randomization systems emerged over a dozen years ago it seemed that some of these new systems might eliminate the need for standalone CTMSs. That has not proven to be the case. The need for CTMS is still important for sponsors, CROs, and sites.  

Many technology systems are touted to include "business intelligence" or digital dashboards and compatibility with other systems. It's also become common to include compatibility and integration with other data management systems as a core capability of eClinical systems, but it's more difficult to implement in ways that are meaningful and beneficial to end users.  

This was the case with Palm Beach Research Center, an investigation site that conducts Phase I-IV clinical programs. Laurie Jassenoff, MBA, Vice President of Palm Beach explains, "Today, to get any kind of information on a clinical research program we have to query a particular database. If we want to look at studies, that's one database. If we want to look at studies with patients, that's a different database. It takes a lot of extra time and effort. When I log into my bank account I can view all my accounts at once. It would be great if as a researcher I could sign on to one integrated database with the same kind of front page to access all the information I need." 

And while many systems can integrate with other systems, providing compliance and industry standards capabilities, there are cost and time considerations to integration that must be accounted for. Because integration can be difficult, many organizations can end up using different data sources during trial conduct and go through the process of merging data at the end. Janssenoff says, "for example, it would be a huge time saver if we can enter our source data and it merges with the eCRF." 

Palm Beach Research Center is rolling out a CTMS in 2013. "Our goal is for the CTMS to become a huge patient database that will be able to show cross references of studies and patients, and patients in studies, in addition to having budget information integrated to show what we are invoicing and what is outstanding." Jassenoff said, "Ideally I'd like to be able to review this integrated data on my iPad anywhere, any time."  

CTMS integrations make a great deal of business sense. The combined data streams provide real-time trial information that may come from ePRO, IVRS, and EDC systems that roll directly into CTMSs and roll up into a real time view of a trial.  

How will CTMS look 10 years from now? That's what vendors and organizations alike are contemplating.  

The likelihood seems strong that cloud-based computing will make it easier to provide meaningful dashboards from data across trials. The resulting information should flow more easily across systems into data warehouses and reporting servers that provide that actionable knowledge to a variety of stakeholders about the way trials are run.  

—Sheila Rocchio, Vice President of PHT Corporation