Vice President, Patient Centered Solutions, IQVIA

Jean Paty

The term patient centricity has become a mantra for the pharmaceutical industry. However, life sciences companies should think about the need to move beyond abstract commitments to “patient-centricity” and rather embrace patient-centered science as a foundational approach across all stages of the product lifecycle. A crucial component of this entails actively listening to the most important stakeholder—the patient—and using scientifically rigorous patient-relevant data to advance therapeutic innovation.

Understanding the patient perspective, from the patient themselves, has become an ever-evolving and must-have in order for life sciences companies to enhance research strategies, to drive advances in drug development, and to achieve commercial success. This patient-centric initiative is driven by several trends:

Today, patients are more invested and engaged in their own health than ever before. Patients want to understand how they can improve their health and prevent disease. They crave information including access to their own health data, and many patients are willing to share their health data.

 However, while credible and accessible information is important; bad health information used in an improper way can be highly detrimental.

 Many people turn to Wikipedia for information—it was the eighth-most-visited website in 2020

 and a recent systematic review highlighted it as ranking highly in Google searches for health information and as a resource accessed frequently by the public for this aim.

 A study analyzing Wikipedia articles of 10 medical conditions, including diabetes, found statements on the webpages discordant with the latest medical research at the time in 9 of the 10 entries.

Technology has become a powerful enabler of the patient perspective through a constantly growing array of personal health technologies, such as smart phones, sensors, and other remote technologies. Just think about all the devices on the market that track everything from heart rate to stress levels. Patients have an abundance of their own personal data they can use to inform their health decisions. However, this technology is rarely being utilized to its full potential in clinical research

 and is not currently being used in routine healthcare.

Science has deepened the understanding of and ability to advance more individualized and tailored treatment options enabling patients to make shared decisions with their providers. There have been significant advancements in understanding treatment effects, identifying responders, and incorporating patient needs, perspectives, and priorities into treatment decision-making, but the tools are not always there to support it.

Regulators and payers increasingly recognize the value of applying a patient perspective in research and decision-making, although this is done inconsistently.

Challenges in the adoption of patient-centered science

To generate patient-relevant research data that can be used to support regulators, payers, healthcare professionals, and patients in making well-informed and reliable decisions, it is essential that scientific approaches are taken. Patient-centered science is evolving as an evidence-based approach for the life sciences industry, which provides a more rigorous scientific underpinning to adopting a patient perspective than a lofty declaration of patient-centricity.

However, adopting patient-centered science has its challenges for life sciences companies. Such challenges are reflected in the current communications of clinical endpoints and in engagements with patients around data:

: In the past, life sciences companies have relied on endpoints that don’t always resonate with patients. As an example, in diabetes HbA1c—a 3-month average marker of blood glucose control—is used as the traditional indicator that clinicians rely on as part of the diagnosis and clinical decision-making, but the blood glucose markers that patients rely on for their own decision-making are fundamentally different—with fluctuations and daily control key. Further, behavioral modifications needed for successful diabetes control are rarely built into the endpoint, so while we aim to understand the impact of treatment on glucose control, it is possible that some of the effect is in fact a result of behavioral changes.

: Many people don’t have the ability to understand and respond to health information. A 2015 survey suggested that 43% of English adults possess insufficient literacy skills and 61% possess insufficient literacy and numeracy skills to routinely understand health information.

 This pertains to both the collection of quality data directly from patients (which inherently assumes a level of health literacy to reliably understand and respond to the questions asked about their experiences) and the dissemination of relevant data to patients.

: Communicating clinical information is not as easy as it sounds. This is increasingly challenging with the rapid evolution of complex science, specifically in the areas of genomics and precision medicine. There are boundless opportunities for life sciences companies and health care professionals to provide clinical and scientific information to a patient in a way that is relevant, understandable, and actionable. However, the traditional approach by clinicians to lead clinical decision-making is only slowly being replaced by shared decision-making where the patient and physician partner around the decision-making.

: The role of cultural and ethnic bias has also been poorly understood, which has limited the understanding, acceptance, and adoption of therapies and lifestyle modifications among minority populations. It is only recently that the medical community and the life sciences industry has started to address the cultural barriers and health disparities that affect various, diverse populations.

So how do we all work to advance patient-centered science?

Several strategic steps should be undertaken to advance patient-centered science:

: The traditional “push” communications approach where patients are told what to do by the provider or the life sciences company should be replaced by a new paradigm based on listening. This should be done within a scientific research framework as market research and individual case studies can be informative, but neither comprehensive nor generalizable. Fundamentally, the medical ecosystem needs to recognize that the patient is the one suffering from the condition and therefore has unique perspectives, insights, and experiences that should impact all aspects of the patient journey. It’s a learning opportunity for all parties.

Traditional clinical endpoints based on the pathology, physiology, and biology of disease need to be expanded with endpoints that relate to functional ability (sleep, mobility, etc.), and the emotional and psychological patient experience.

: In the era of patient-focused drug development there is a greater use of patient-reported outcome measures (PROMs) in clinical trials. Electronic technology has a key role to play in capturing timely and patient-relevant information to inform study endpoints. There are several areas where technology can be used to enhance patient-focused drug development: Capturing qualitative data from patients; using digital health technology tools; employing reactive technology-enabled clinical outcome assessments; and generating passive patient experience data.

Rethink the application of patient-centered science

: Patient-centered science should be incorporated and adopted across all aspects of the product lifecycle where life sciences companies make decisions about endpoints. This will include the application of Clinical Outcome Assessment (COA) and Patient Experience Data (PED) platforms that intelligently automate capturing patient experiences and information about priorities, preferences, and needs, as well as experiences with treatment, care, and outcomes, through robust and reliable electronic measures, providing real-time insights that inform clinical trial progress and demonstrate results. (See Exhibit. Example scenarios across the product lifecycle where companies may make patient-centered science investment decisions).

: Life sciences companies should aim to overcome the internal fragmentation and silos that impede the ability to think holistically about the patient experience as an integrated approach across the enterprise. This can be a challenge as it may conflict with traditional ways of working in pharmaceutical organizations. It all starts with a few small steps. One example is directly coordinating patient-centered solutions services with the CROs to accomplish more dynamic patient perspectives in clinical trial design, development, and execution.

What does good patient-centered science look like in practice? Albireo Pharma case study

The critically important role of patient-centered evidence was demonstrated in IQVIA’s work with Albireo. Patient-centered science was applied to define clinical endpoints and to secure regulatory approval of a novel drug for the treatment of a rare liver disease in children.

A global rare liver disease company focused on the development of novel bile acid modulators to treat rare pediatric cholestatic and adult liver diseases, Albireo has developed a novel bile acid modulator, odevixibat (A4250), for progressive familial intrahepatic cholestasis (PFIC). PFIC is a rare genetic disorder that causes progressive, life-threatening liver disease in children.

In many cases, PFIC leads to cirrhosis and liver failure within the first 10 years of life. The most prominent and problematic ongoing manifestation of PFIC is pruritus, or intense itching, which often results in a negative impact on the daily lives of patients and caregivers. Until last year, there was no approved drugs for PFIC. Only surgical options that include biliary diversion surgery (BDS) and liver transplantation have been available, and without them, most PFIC patients do not survive past the age of 30.

Supported by the global Phase 3 PEDFIC studies, on July 16, 2021, Albireo received European Marketing Authorization for Bylvay® (odevixibat), the first drug approved for the treatment of PFIC in patients aged 6 months or older. Four days later, on July 20, 2021, FDA followed up with a similar approval of Bylvay (odevixibat) in the U.S. for the treatment of pruritus in patients 3 months of age and older with all types of PFIC.

“Until now invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” said Emily Ventura, leader of 

 and mother to a PFIC patient. “As a community, we experience extreme challenges and diminished quality of life for children and families with PFIC. Managing the symptoms can be extremely difficult—the burden is unimaginable with our kids suffering physically, emotionally, and developmentally.”

Albireo harnessed patient-centered science from the very beginning of the development program for Bylvay, and its experience illustrates the points previously discussed.

 Through semi-structured interviews with patients and/or their parents and clinical experts Albireo was able to understand the unique experience of PFIC patients and to develop a measurement tool for the pruritus symptoms and impacts (e.g. sleep disturbance) which was presented to regulatory authorities.

: Albireo selected a truly patient-centric primary endpoint by measuring both a pruritus improvement endpoint, and a serum bile acid endpoint as primary endpoints in its pivotal trials.

: Through a well-designed, patient-friendly eDiary, patients and/or parents reported their experience of pruritus and other aspects of PFIC, twice daily throughout the trial. Albireo’s strong engagement with parents ensured that completion rates for the eDiary were high throughout treatment.

: Albireo implemented an end-to-end patient-centric strategy that began in Phase I and continues in patient support programs and real world studies.

IQVIA has been the scientific partner for Albireo throughout this journey. We look forward to seeing how this information is shared with HTA/payers, patients, and HCPs to support reimbursement decisions/formulary placement, and inform clinical care.

Achieving benefits from patient-centered science

Capturing the patient perspective can generate more relevant, valuable insights that can help drive better outcomes for life sciences companies and, at the end of the day, achieve what we should all put front and center: improved patient outcomes. Companies doing this can claim to be truly “patient centric.” Benefits of capturing the patient perspective include:

Improved understanding of the patient experience across the product lifecycle by listening to patients

Enhanced data transparency and quality by enabling patients to better understand the importance of evidence-based endpoints in clinical trials—technology-enabled endpoints can further increase reliability and validity of the data

Patient-informed clinical trial designs which maximize recruitment and retention

Harmonized clinical, commercial, and access decisions across the organization

Reduced study implementation timelines that accelerate access to new therapeutic innovations

These benefits of “patient centricity” can only be fully realized with an emphasis on good scientific principles and practices. If these data are to inform pivotal decisions in pharmaceutical/biotech companies, among regulatory and payer organizations, and in HCP-patient communications in routine clinical practice, they need to be well informed, reliable, non-misleading, and easy to interpret. As such, patient-centered science is emerging as a pivotal effort in medicine along the entire product lifecycle, redefining “patient-centricity” as the generation of patient-relevant and scientifically sound data which is both representative of, and generalizable to, the target population for the treatment under investigation. In this way it is translating the voice of the most important stakeholder—the patient—into relevant data to advance therapeutic innovation. Now it needs to become the mainstay, if not the only way in which patient centricity can be claimed.

, Vice President, EMEA Lead, Patient Centered Solutions, 

, Vice President, Patient Centered Solutions, and 

, Senior Principal Scientist, Patient Centered Endpoints; all with IQVIA

PEW Research. Most Americans Want to Share and Access More Digital Health Data. 

https://www1.pewtrusts.org/en/research-and-analysis/issue-briefs/2021/07/most-americans-want-to-share-and-access-more-digital-health-data

Tonsaker T, Bartlett G, Trpkov C. Health information on the Internet: gold mine or minefield? Can Fam Physician. 2014;60(5):407-408. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020634/

Cooke, R. Wikipedia is The Last Best Place on the Internet. WIRED. February 17, 2020/ 

https://www.wired.com/story/wikipedia-online-encyclopedia-best-place-internet/

Smith DA. Situating Wikipedia as a health information resource in various contexts: A scoping review. PLoS One. 2020 Feb 18;15(2):e0228786. 

https://pubmed.ncbi.nlm.nih.gov/32069322/

Hasty RT, Garbalosa RC, Barbato VA, Valdes PJ Jr, Powers DW, Hernandez E, John JS, Suciu G, Qureshi F, Popa-Radu M, San Jose S, Drexler N, Patankar R, Paz JR, King CW, Gerber HN, Valladares MG, Somji AA. Wikipedia vs peer-reviewed medical literature for information about the 10 most costly medical conditions. J Am Osteopath Assoc. 2014 May;114(5):368-73 

https://pubmed.ncbi.nlm.nih.gov/24778001/

Reaney, M., Cline, J., Wilson, J.C. et al. Generating Relevant Information from Patients in the Technology-Enhanced Era of Patient-Focused Drug Development: Opportunities and Challenges. Patient 14, 11–16 (2021). 

https://link.springer.com/article/10.1007/s40271-020-00455-2

QVIA Institute for Human Data Science. Digital Health Trends 2021. Juky 22, 2021. 

https://www.iqvia.com/insights/the-iqvia-institute/reports/digital-health-trends-2021

Rowlands G et al. A mismatch between population health literacy and the complexity of health information: an observational study. British Journal of General Practice 2015; 65 (635): e379-e386. 

Articles

Good scientific principles and practices are essential for maintaining quality data that patients can benefit from.

Harnessing Patient-Centered Science to Improve Health Outcomes and Commercial Pharma Success

I cannot believe FDA did it again. For two years in a row, FDA comes out as the leader, pushing our industry forward. At the end of 2010, we thanked FDA for encouraging us to listen to the patient. This came through loud and clear in FDA's publication and promotion of their patient reported outcome (PRO) guidance at the end of 2009. PROs are direct reports from the patients that are not interpreted by a health professional. The propagation of PROs across product development programs, and the appearance of new PRO-based labels in the past two years is clear evidence we in the industry are hearing FDA's message. 

 In 2011, FDA went yet another step by telling us that there are multiple ways to give the patient a clear voice in clinical research. Specifically, FDA stated that we need to ensure all of our measurements and outcomes, not just PROs, reflect what is happening with the patient. In other words, we need to provide evidence that all of our instruments or tools measure what we think they measure. In FDA terminology, we must ensure that instruments or tools and their related outcome measures are fit for purpose in their context of use.  

Specifically, this means that instruments based upon a clinician's evaluation of a patient (ClinROs), and measures taken by an observer (ObsROs), like a mother reporting about her child, are subject to the same requirements for reliability and validity as PROs. FDA expects that all outcomes assessments (OAs)—ClinROs, ObsROs, and PROs—will meet 21CFR314.126(b)(6) requirements that "the methods of assessment of subjects' response are well-defined and reliable." The recommendations of how to meet the well-defined and reliable standard are delineated in the PRO guidance. In other words, FDA is using the PRO guidance as the yardstick by which it measures all OAs. 

The announcement regarding OAs came during an FDA-sponsored workshop held on October 19, 2011 at the FDA White Oak Campus in Silver Spring, MD. Both FDA and the industry were represented at this one day workshop. Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research, gave the opening address and set the stage for OAs: 

 "Now clinical trial outcome assessments are one type of drug development tool that we have identified as ripe for improvement. The identification, development, and qualification of new clinical trial outcome assessments is an area that has really not been aggressively pursued by the scientific community, and the lack of—the consequent lack of assessment tools has been impeding, I think, the successful development of new drugs because we really in many cases don't know how to measure the impacts, both for good and ill, of the drugs that we test in people. And we can do better." 

This challenge from Woodcock also provides opportunity. OAs that are well-defined and reliable can support novel labels for our products, which in turn differentiate them from other treatments. There is now a defined regulatory pathway to novel product labeling. 

It is refreshing to see that regulators are prepared to help us in the industry meet the challenges of bringing new products to market, and most important, to create a pathway of success for these products. What do you have planned for 2012, FDA? 

, Senior Vice President, invivodata, Inc. 

All measurements and outcomes need to reflect what is happening with the patient.

Give the Patient a Clear Voice

Subject diaries are used  to collect primary and secondary endpoints in about 25% of all clinical trials.1 In recent years, the traditional paper diary booklets have been replaced in some instances by small electronic devices for recording diary information.2 Our series of articles is aimed at helping clinical researchers understand the development, implementation, and regulatory compliance of these electronic patient diary systems. Our particular focus is on the reasonable apprehensions expressed by clinical teams considering whether to use electronic diaries. They worry about these issues.	

Lack of clarity about complying with the regulations governing electronic systems (discussed in Part 2)

Lack of knowledge about how an electronic system is specified, built, and deployed

The effect of including an electronic diary in the clinical trial development process and timelines

The number of work process changes that could be required of participants in the clinical trial process: sponsor staff, monitors, investigators, and subjects. 

To address these concerns, this series presents the clinical, technical, and regulatory issues involved in the development and implementation of electronic patient diary (EPD) systems that meet regulatory requirements. Part 1 compared paper and electronic methods in the context of existing FDA and ICH regulations and guidance for capturing diary data.3 We concluded that newer, electronic methods are in fact more compliant with FDA and ICH data standards than traditional paper diaries. In Part 2, we began discussing the clinical and technical considerations for developing an EPD system. We focused on the clinical protocol and its definition of the medical moments-the health experiences-to be recorded by the subject, and we concluded that it is key to the success of an EPD system.4	

In Part 3 we discuss the development and validation of an EPD system based upon a clinical protocol. As shown in Figure 1, a computerized EPD system extends beyond the hardware and software used by the subject. It also includes the systems components and work processes for all users of the system; the core of the EPD system is the diary device containing protocol-specific software. The device also requires some type of communication software and hardware-for example, a peripheral wired modem that connects to a regular phone line-to transmit the subject data to a central data repository or server.	

Figure 1. Computerized system for electronic diaries.				

Once it is on the server, the subject's data can be processed and viewed in a secure environment by those responsible for trial management and conduct. The investigative site can use this information to evaluate the subject's compliance with protocol procedures. The sponsor's clinical team can review the data from the server to monitor the investigative sites' activities and to assess the subjects' performance. The components of a successful EPD system include the activities carried out by the subjects and the trial managers as well as the hardware and software. 	

The key players in developing an EPD system are the clinical team responsible for the trial and a technical team that brings the EPD technology and the expertise to customize the technology for a particular trial. To design and develop an EPD system that meets the needs of the protocol takes close collaboration between those two teams. Many aspects of the collaboration should be familiar to the clinical team, given that every trial requires a well-coordinated effort between the sponsor, CRO (where appropriate), investigative sites, and subjects.		

Unique features of the collaboration of the clinical and technical teams are the development of the EPD technology and the support structures-training materials, for example. This development, however, should be greatly facilitated by the technical team's expertise. The result should be that the experience of developing an electronic diary system and then executing the trial in which it is used should feel much like that of any trial for a clinical team. 	

A successful collaboration of the clinical and technical teams depends upon clearly defined responsibilities, tasks, and deliverables. Figures 2 and 3 diagram the tasks required to develop, implement, and eventually retire an EPD system in the context of a clinical trial. Figure 2 illustrates the system development life cycle (SDLC), activities primarily driven and executed by technical team. Figure 3 depicts an EPD clinical trial life cycle (CTLC), which summarizes the activities and support structures needed, mapped onto the typical steps involved in planning, launching, executing, and closing out a trial. CTLC activies are driven by the clinical team and executed through collaboration of the clinical and technical teams.	

In Part 2 of this series we discussed Steps 1 and 2 of these life cycles, the development of a clinical protocol and the user requirements specification (URS) for an EPD system. Assuming a clear set of specification documents for the system, we focus here on Steps 3 through 6 of the SDLC and CTLC, or the preparation of EPD system for trial launch. The two streams of activities that occur during preparation are the building and testing of the EPD software (SDLC), and the development of all of the support infrastructures for the software (CTLC). 	

Details of the tasks, responsibilities, and deliverables at each step are described below. As in any GCP study, an essential component of all of these activities is careful and clear documentation of the process. Figure 4 diagrams the computerized system validation (CSV) documentation that results from this documentation. The outcome of Step 6 in the system development life cycle and the clinical trial life cycle (diary acceptance) is a validated electronic diary system that performs as intended.	

Infrastructure (Paty, clinical-regulatory) Once a protocol is approved, the clinical team begins to establish the infrastructure for the study. This includes selecting a CRO, if one is to be used, and sites for the study. The sites do not need to be technically proficient if the EPD system is designed with end users in mind. In our experience the most important site qualifier is willingness to learn something new. Of course, if the site has previous experience with an electronic diary system, this can significantly aid the implementation of the trial. For many EPD systems, the infrastructure requirements for sites are minimal: a regular phone line and Internet access. 		

Figure 2.  The System Development Life Cycle (SDLC).				

Equipment selection and purchase is another component of preparing for an electronic diary system. With the technical team's advice, the clinical team makes the final decision about the hardware best suited for the subject population being recruited for the trial. Subject hardware includes the data collection device and possibly communications hardware (an attachable wireless or wired modem, for example). 	

Investigative sites may need specific hardware to support the system, but for systems that rely on the Internet, sites may simply require Internet access and standard browser software. The same applies to the sponsor and/or CRO staff. For global trials, the subject hardware selected needs to support multiple languages. Communications device needs may differ from country to country given variability in wired and wireless capabilities in Europe, Asia, and South America. Once the hardware decisions are final, early procurement ensures that equipment is not a bottleneck in developing and launching the trial.	

Diary design (Stokes, technical-regulatory). Steps 1 and 2 in the EPD system development life cycle translated the clinical protocol into a user requirements specification (URS). The technical team's first action in diary design is to translate the user's view of a diary (their URS) into the functional requirements specification (FRS), a technical document that describes the EPD system in a way that a programmer knows what has to be built (Figure 2, Step 3). To maintain the integrity of the original protocol throughout the validation of the electronic diary, the technical team creates a traceability matrix that links the requirements in the protocol to those in the URS and then to the FRS. The traceability matrix has a central role in ensuring that anyone can begin with the protocol and trace through all of the documents to ensure the system was built as specified. 	

Traceability matrix. It is important to create a traceability matrix showing how the URS addresses the Protocol sections and how each and every URS statement is addressed by one or more FRS statements. Here are some examples of protocol statements with corresponding URS and FRS statements.	

Protocol statement (from clinical team). "Weekly Assessment: The following question will be assessed approximately every seven days during treatment period as part of the subject's daily assessment . . ."	

URS statement 24 (from clinical team). Flow chart made to show Q&A dialogue for daily assessment and also the insert prompt for a weekly summary assessment.	

FRS statement 53 (URS 24) (from technical team). Screen prompt question is "Answer the following item according to how you have felt during the past week." This prompt and subsequent dialogue is to show in the EPD on study days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77. 	

The system design description (SDD). In order to tell the programmer how to build the diary, the technical team converts the FRS statements into a system design description (SDD). Usually a design description statement covers more than one FRS statement. Thus, an item-for-item traceability to the SDD is not useful, but an overall system design review should be performed to ensure that all the FRS statements have been covered somewhere in the system design. Taking the FRS example described above, the appropriate SDD statement (from technical team) would be		

Figure 3. Electronic patient diary clinical trial life cycle (CTLC).	

Code the system with a study-day tracking variable (variable SD4) so that the EPD tracks the current Study Day number. Code the Daily Assessment to always check variable SD4 whenever it is called in the code and to check if the Study Day (SD4) is day 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, or 77. If Study Day matches, then code system to display extra dialogue item as per UR24. If no match is made, then code so that no extra display is issued to the EPD user.	

The process of moving from protocol through to functional requirements and software design is usually an interative one. It can be readily accomplished with consistent and effective communication between the clinical and technical teams. After several EPD trials, when the clinical team learns the capabilities of the technology, it can refine the protocol statements to more easily translate into functional requirements. The technical team can then develop standard diary modules and the whole EPD development process becomes faster and more efficient.	

Software review, training, and plans (Paty, clinical-regulatory) With the sites selected and the technical system specifications written, the clinical team-with considerable support from the technical team-can focus on planning and implementing various components of the EPD system. They can				

Review and approve EPD software prototypes 

Develop a plan for deploying units during the study.

Software review. A very important component at this stage of development of the EPD system is a clinical team review of alpha (early stage) software. This review allows the clinical team to determine whether the technical team is developing software that accurately reflects the protocol. Most important, it is an opportunity for the clinical team to determine whether the software is "coming alive" in the way they had expected. If it is not, this is the time to pause and reconsider the design of the system and its specifications. When the clinical and technical teams collaborated during the specification process, the typical outcome of the alpha review is making only a few minor changes to the system.	

Training materials. In an EPD study, concise and clear training is essential for all users of the system. 21 CFR 11.105 states that persons using an electronic data capture system need to be appropriately trained on the system. Training materials need to be developed for the different user groups-subjects, the investigative site staff, sponsor/CRO clinical research associates (CRAs), and other study management staff. The technical team often provides a core set of training materials that are customized for the specific trial. The customizing requires knowledge of the protocol and the system, suggesting a clinical-technical team collaborative effort. 	

Help desk. Another component important to the planning of an EPD trial is a plan for a technical help desk that will support the study. The clinical team's input is important here, because the technical help desk will be dealing with the subjects, the investigative site personnel, and the CRAs. As such, help desk personnel will need to understand how to address technical issues that may be specific to the EPD protocol. The technical team provides the technical details, and the clinical team provides protocol-specific content. That content is then reflected in scripts for the trial that guide help desk personnel who respond to questions from the trial participants. In multinational trials, the scripts can be developed so that they can be readily translated to all relevant languages. Implementing the scripts and general management of the help desk is typically the responsibility of the technical team.		

Figure 4. Electronic patient diary computerized system validation (CSV) package model.	

Equipment deployment. The clinical and technical teams will plan the provisioning (loading software onto the EPD units) and shipping of equipment to investigative sites. Their plan needs to take into account the exact provisioning process, who will perform the activity, how and when units will be shipped to sites, and the timing for returning units from the investigative sites. Given that some trials are conducted with thousands of subjects in several countries, a well conceived plan for provisioning and shipping is an important component of trial preparation. The clinical team will provide input based upon knowledge of the sites' locations, and the technical team will delineate the process and manage the provisioning and shipping process. 	

Data management. The data management and statistical groups may begin their planning at this point. Based on the database design described in the specifications, the sponsor-CRO data management team can work with the technical team to ensure that the method and format for delivering the data is clear. This will ensure that data can be delivered regularly to the sponsor or CRO for inclusion in the clinical database. 	

CTLC Step 4 summary. Once the planning, development, review, and approval activities have established the support stucture for an EPD study,	

the materials are prepared to train the system users.

the plan is in place to support the users if/when they have questions or problems.

the plan is in place for getting the EPD devices to sites for subjects.

the plan is in place for delivering data to the sponsor.

The clinical team is ready to initiate sites for the trial, hold the investigator meeting, and launch the study. 	

The study protocol and a set of specifications are the road map for developing the software and the support structures for an EPD study.

Jean Paty

Articles

Harnessing Patient-Centered Science to Improve Health Outcomes and Commercial Pharma Success

Give the Patient a Clear Voice

Developing and Validating Electronic Diaries