Christine Hall

	The specialized industry of collecting patient-driven eData is increasing exponentially. Patient-driven eData encompasses all electronic clinical outcome assessments – or eCOAs -- including patient reported (PRO), clinician reported (ClinRO) and observer or caregiver reported outcomes (ObsRO). This is because global government regulators want to hear directly from the patient, and because the acceleration and availability of electronic collection (vs. paper collection) improves data quality and efficiencies for data analysis and trial management. This article reviews the eCOA market and outlines the five eCOA methods that successfully support the collection of patient-, clinician- and observer- reported outcome data.

	While paper diary collection is the default method for many latent adopters of new technologies, electronic capture of clinical outcome assessments is growing steadily as sponsors realize the revenue advantages of more accurate, attributable patient-reported data.

	The eCOA market was valued at $200M in 2012 and is expected to reach $265M in the year 2015. The market has grown at a Compound Annual Growth Rate (CAGR) of 8.5% between 2008 and 2015. Increasing penetration of these solutions is the main factor responsible for the growth.

	Recommendations for collecting eCOA measures have been set forth by the FDA Guidance for Industry, Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims,

 the Reflection Paper on the Regulatory Guidance for the Use of Health Related Quality of Life Measures in the Evaluation of Medicinal Products,

 and guidelines from other regulatory agencies.

	Clinical trials using eCOA measures should be designed so:

		Endpoint models are clearly associated with the intended claims

		Measures are fit, reliable and sensitive to change

		The conceptual framework of eCOA instruments is well defined

		Evidence is compelling that eCOA data collection was completed at times specified in the protocol

	As a result of these guidances, the process of collecting electronic patient, clinician and observer-reported outcomes requires much more than a collection device, database, and an instrument.

Five Reliable Collection Methods and Devices Used to Collect eCOAs 

	The rapid proliferation and adoption of smartphone technology is advantageous to COA data collection, since patients are more likely to own their own smartphone and require little or no training. If the eCOA device is used to collect endpoint data to support a claim, regulators require consistent measure displays, data security and compliance with strict guidelines. All of these collection modalities must be used with a backend system that securely receives all data sent in accordance with regulations and guidelines.

	All eSource systems must provide authorized investigator staff with the ability to prepare and maintain eSource records throughout the life of the trial and beyond. When used to collect symptom data for post-marketing purposes, such requirements may not apply.

	Each eCOA collection method and device must be thoroughly vetted in order to comply with various FDA, EMA and country regulations and requirements for trustworthy data. As a result, there are currently five proven and tested eCOA technologies used by sponsors:

		Smartphone – Electronic data capture on a provisioned or existing SmartPhone that sends data to a central system for web review

		IVR (Interactive Voice Response) – Keypad or voice data capture with a central system that allows for web review by site and sponsor

		Web Browser – Browser data capture with a central system that allows for web review by site and sponsor

		Pen – Digital pen that captures data and uploads to a central system that allows for web review

		Tablet – Electronic data capture on a tablet mobile device with a central system that allows for web review

	Following is a review of each collection option, recognizing that the ideal method of acquiring patient-reported data is contingent on each trial’s indication, size, complexity, length, locations, survey elements, patient population, budget and critical success factors. Further, each may be used by itself or in a combination with others, depending on how the study protocol prioritizes the preceding criteria.

Smartphone: Electronic data capture on a provisioned or existing device

	Smartphones are preferred for collecting data from patients in transit. They can be integrated with medical devices and other technologies to combine objective measurements, and with IVR to streamline patient enrollment and randomization.

	Similar to all devices that capture COAs, smartphones provide patients with the logically appropriate questions and items at the correct times, simplifying diary completion and ensuring that sponsors receive reports with entirely logical response structures. Smartphones are especially useful for protocols that require data from frequent or episodic incidents. Patients can be prompted to fill in responses according to the protocol time guidelines via alarms and reminders, and only allowed to enter diaries within specific time windows. This provides cleaner data than paper diary collection, and makes integration with a reminder system unnecessary.

	These devices collect data in complete, logical and legible formats and may use a stylus which may be attractive to patients with challenging hand/eye coordination, arthritis, or tremors. The use of Smartphones in eCOA Systems can streamline mid-study changes by deploying changes seamlessly from a centralized server, at a scheduled time.

	The second most frequently used method to collect eCOAs is IVR, due to its prevalence in a wide variety of applications available on the market. IVR is familiar to use, and is favored over paper diaries for branching logic and data integrity. Like smartphones, IVR can streamline mid-study changes by deploying changes seamlessly from a centralized server, at a scheduled time.

	IVR presents usability challenges for countries without advanced phone systems, and for surveys with lengthy or complex questions. Its capacity to collect patient data is impeded by the public’s low tolerance level for calls longer than five minutes. Further, IVR compliance can be strained when study participants lose track of, or tire waiting to hear, the entire list of response options, which can bias them to select the first option provided. IVR also limits the ability for clinical researchers to ask all the requisite questions. Unlike smartphones, IVR systems do not have the capacity to display graphical elements nor visual scales.

	As a result, IVR technologies are employed for short and simple diaries or (more commonly) integrated with smartphones to streamline enrollment and randomization.

	The Internet is gaining popularity as an eCOA collection modality, as global populations gain access to the Internet on a reliable basis. Like any mobile device, a browser can execute complex and lengthy diaries and questionnaires with images and visual scales, and streamline mid-study changes by deploying changes seamlessly from a centralized server, at a scheduled time.

	Browser-based eCOA can be employed at the clinician site or at the patient’s home, office or school, but regulators require that it be located in a private setting with a reliable Internet connection. If used outside the clinical setting, the patient must be near the browser for episodic or frequent diary collection.

	Browser-based eCOA Systems have successfully captured data on desktop computers and tablets. For acceptance by regulatory authorities, any new instrument must be proven to display consistent diaries and questionnaires on each screen, without bias.

	The pen relies on the patient using a unique writing instrument on special paper printed with the diary or questionnaire. It cannot prevent patients from skipping answers, entering illogical data and entering data outside of protocol specified time windows. Since sites and patients must use assigned papers and a pen, the cost for pen eCOA collection includes all the duplication, transportation and redundant data entry costs of paper diaries plus the added expenses of unique pens.

	Contrary to a smartphone, IVR or browser-based eCOA Systems, the pen requires extensive cleanup of data towards the end of the trial, and yields significantly less valuable data per patient. It cannot provide real time feedback in the language of patients, and must be combined with a reliable reminder system, to ensure date entry dictated by the protocol.

	As a result of its limitations, the pen is used for simple, short and/or infrequent diaries and instruments.

	Tablets are popular for site-based data, where they are often used to collect patient, clinician and observer-reported outcome data. Tablets are used by patients and clinicians at the site. They can update drug inventories and other calculations to streamline burdensome, costly clinical administration. Currently, tablet provisioning is a cost-effective solution for collecting multiple patient questionnaires at the site.

	Like smartphones, tablets collect data in complete, logical and legible formats. Some are touchscreen; others use a stylus which is attractive for patients with challenging hand/eye coordination, arthritis, or tremors. Tablets are ideal for collecting data using long and/or complex questionnaires, as within protocols with Alzheimer’s, Arthritis, Hep C, Oncology and Psychiatric indications. They can be ideal to view VAS scales and images, and streamline mid-study changes by deploying changes seamlessly from a centralized server, at a scheduled time.

	Tablet eCOA data collection at clinical sites will continue to increase with the proliferation of new tablet technologies and Internet access. Patients and sites enjoy using the large, bright touchscreens the tablets provide with plenty of display room and simple transmission via WiFi, 4G and Ethernet.

	Each of the five distinct eCOA data collection methods has been used for successful data submission to regulatory agencies. Each has specific utility for protocol requirements. As technologies broaden and data collection devices become more common, the eCOA System will be the determinant for delivering high-quality patient driven eData.

	1 GBI Research, ‘The Future of eClinical Trial Solutions–Market Forecasts to 2015, Competitive Benchmarking and Case Studies, pp53-54, December 2009.

	2 U.S. Department of Health and Human Services, Food and Drug Administration, December 2009.

	4 Other global regulatory agencies include the Pharmaceuticals and Medical Devices Agency, Japan; European Union, the International Conference on Harmonization; and other country-specific government agencies.

Christine (Chris) Hall can be reached at 

Articles

The specialized industry of collecting patient-driven eData is increasing exponentially. Patient-driven eData encompasses all electronic clinical outcome assessments - or eCOAs -- including patient reported (PRO), clinician reported (ClinRO) and observer or caregiver reported outcomes (ObsRO).

Comparing the Five Methods to Collect Patient-Driven eData

As such, biopharmaceutical companies and researchers around the world are working to identify new, effective and safe treatments to help this growing patient population.

	Diabetes clinical research often includes patient reported outcomes (PROs) to measure symptoms and safety over the course of the trial, quality of life, and the economic burden of the disease. Data are collected directly from patients on diaries and/or questionnaires, which are either printed on paper or available on electronic devices.

	The use of electronic patient reported outcome (ePRO) data in clinical research is increasing as regulatory authorities acknowledge the credibility of such data, particularly in comparison to paper and pencil self-reports completed in unsupervised settings. Many sponsors leverage technologies by collecting symptom, event, and quality of life (QOL) data on the same electronic platform. This simplifies and streamlines the entire data collection and management process.

	Transitioning a diary or questionnaire from paper to electronic formats requires physically modifying the appearance of the diary or questionnaire to fit on the screen of a device. The primary goal when transitioning from the use of paper questionnaires to versions administered electronically is to preserve psychometric validation by minimizing the degree of change between the paper version and the electronic one. The likelihood of comparability or measurement equivalence of the ePRO version to the paper one depends on the degree to which there is modification of the content, format, and usability of the PRO items and scales.

	This article highlights the conversion from paper to ePRO for a PRO instrument designed to assess the impact of diabetes on the quality of life of patients with diabetes.

	Diabetes programs are similar to other therapeutic areas, but often require these additional components:

		Patient data collection at various locations-the site, at home, at work, at school, etc.

		Study designs with inclusion and exclusion criteria that involve daily measures during screening.

		Complex randomization schemes and various defined treatment regimens.

		Requirements for treatment and management of emergent events anticipated with these patients.

	For many sponsors and clinical research organizations the decision to collect patient data on paper diaries or electronic ones is an economic issue. When the trials or studies are not collecting endpoint data, the disadvantages of paper methods may be manageable. If the data are intended to support an endpoint with the diabetes trial or study collecting data for submission or post-marketing verification, the following issues with paper become too expensive in terms of risk and resources:

		Real-time data are not available to support timely enrollment decisions, to manage compliance, to detect emerging problems in the trial, or to support adaptive trial designs.

		Incomplete diaries and reports are common.

		Safety review teams and regulatory authorities must work from low quality records.

		Logical inconsistencies in the records occur as subjects fail to follow conditional branching properly, usually necessitating the expense and difficulty of source data verification and clarification.

		There are no real-time automated alerts if symptom thresholds or other criteria are exceeded.

		Contingent messages and reminders to participants are more difficult to generate and are delayed.

		Side effects and unexpected problems that deserve review by investigators are unstructured and unavailable in a timely fashion.

		Recall bias is introduced when subjects do not complete PROs according to the protocol's schedule. This bias can obscure real signals from the study medication.

	Of the five different ways to collect ePRO, many sponsors and CROs prefer the tablet, smartphone (handheld) and Internet for diabetes research. The digital pen and integrated voice response (IVR) do not integrate with glucometers to capture blood glucose levels automatically. Handheld patient data collection devices as well as Internet-based systems have been used to collect ePRO symptom and safety data, and integrate that data with glucose readings recorded directly from wireless connected glucometers.

	Tablets, smartphones, and the Internet provide easy-to-read screens for electronic diaries and questionnaires, enabling clear question displays and unambiguous areas for touch-screen or stylus responses. Companies in the ePRO industry have managed many trials for diabetic neuropathy, diabetes, diabetic peripheral, and neuropathy indications. There are a number of standardized questionnaires implemented on ePRO devices:

		Insulin treatment satisfaction questionnaire

	DHP-18 for ePRO data collection and analysis

	The Diabetes Health Profile (DHP-18) is a ubiquitous diabetes questionnaire that has been extensively used in its paper form to capture QOL data from diabetes patients. It was developed by co-author Keith Meadows, and was adapted for electronic administration because it has been shown that electronic questionnaires are preferable to paper.

	Diabetes mellitus is a prevalent chronic condition affecting approximately 55.5 million adults in Europe and 29.5 million adults in North America. The long-term health impacts of diabetes may include heart disease, kidney failure, and microvascular complications such as neuropathy and retinopathy. Alongside these health complications, diabetes can also have an adverse impact on the patient's psychological and emotional functioning as well as social activity and behavior.

	The importance of PRO measures in the care and treatment of people with diabetes has gained significant prominence over the past two decades. This has resulted in the development of a variety of diabetes-specific outcome measures to assess the impact of living with diabetes and its treatment including, quality of life, health-related quality of life, health status, treatment satisfaction, and symptoms.

	One such instrument is the DHP-18, which as a quality of life questionnaire was initially developed as a patient self-completion instrument for use across a range of settings including clinical trials, research, clinical practice, and population surveys.

	Derived from the original 32-item DHP-1, the DHP-18 was developed specifically to assess the impact of diabetes-related aspects of psychological and behavioral functioning on the quality of life of people with Type 1 and Type 2 diabetes aged 18 years and older. As such, it offers a significant benefit for example in assessing the efficacy of different treatment modalities such as changing from pre-insulin to insulin.

	Comprising 18-items which are scored using a 4-point Likert type scale, items are summed to provide three subscale scores using a 0-100 metric for: psychological distress; perceived barriers to activity; and eating problems, which despite the importance of eating behavior in the management of diabetes, is largely neglected in the majority of diabetes-specific PROs. The DHP-18 can be administered through a range of modalities including paper, read to the respondent face-to-face, and administered over the telephone, with average completion times of six to eight minutes.

	Globally, the DHP-18 has been completed by nearly 5,000 respondents participating in clinical trials, community surveys, academic research studies, and educational intervention programs both in the United Kingdom and across Europe. At present, the DHP-18 is being applied in the assessment of quality of life in a variety of settings including, Phase III trials across Europe and research projects in Australia, Ireland, Martinique, North America, and national funded research in the United Kingdom. The DHP-18 is also the diabetes-specific outcome measure selected by the UK Department of Health and is currently being used in their pilot study to evaluate the efficacy of patient reported outcome measures for long-term conditions in primary care. Planned international diabetes clinical trials include the use of the DHP-18 in a number of countries including the United States, Canada, China, and Southern and Northern Europe.

	The DHP database comprising information on nearly 5,000 people with Type 1 and Type 2 diabetes who have completed the DHP-18 is currently being utilized to:

		Estimate the minimally important difference of the DHP-18 for both Type 1 and Type 2 diabetes using anchor and distribution based approaches.

		Estimate the association between the DHP-18 responses and EQ-5D utility values by response mapping.

		Develop a shorter version of the DHP-18 using Rasch analysis.

	Reliability, clinical utility, and user acceptability

	The DHP-18 has been evaluated and described as having good evidence for reliability and internal and external construct validity and is one of the few diabetes-specific outcome assessment instruments to have involved diabetes patients in its development.

	The clinical utility of the DHP-18 has been demonstrated by its ability to discriminate between patients groups treated with insulin, oral treatment and diet, presence of microvascular complications, weight gain, non-adherence to treatment, and severe hypoglycemic episodes.

	To further enhance the clinical utility of the DHP-18, work is in progress by a team led by John Brazier, Professor of Health Economics at the University of Sheffield to derive utility scores for the DHP-18.

	To date, the DHP-18 has been administered mainly as a patient self-completion pencil-and-paper format. It has been shown to have high user acceptability with questionnaire postal response rates of approximately 70% and total item completion rates of 90%. Results from cognitive debriefings across a wide range of language groups have also shown there to be minimal difficulties in patients understanding of the meaning of the 18 items.

	The paper version of the DHP-18 has been translated to 26 languages for use across Europe including Bulgarian, Czech, French, German, Slovak, Slovenian, Spanish and Swedish. The DHP-18 has also been adapted for use in the United States (English) and Canada (English and French) and is currently being adapted for use in a further three languages including Mandarin.

	Creating and validating for electronic collection

	Despite evidence of patient acceptability, high-item completion rates, and the overall integrity of data collected using the paper version of the DHP-18, there is both a strong scientific and business case for the creation of a validated electronic version of the measure, eDHP-18. Electronic patient reported outcomes are increasingly being seen as essential by clinical trial sponsors for ensuring data integrity and regulatory support.

	Although paper-based PROs are an established and accepted medium which are easy to reproduce and distribute, ePROs offer a number of distinct advantages over paper. Apart from enabling administration of the eDHP-18 in a consistent, standardized, and objective manner, a key advantage is the ability to date and time stamp PRO data to avoid the recognized limitation of paper-based PROs "parking lot effect" where study participants retrospectively and prospectively enter data-often in the parking lot before their follow-up appointments.

	Further benefits of the DHP-18 for electronic data capture include the ability to integrate eDHP-18 data with other electronic data capture, for instance primary clinical endpoints such as patients HbA1c levels; and, extend to web-browser data collection.

	Migrating from paper to electronic data collection is a significant movement in the field of PRO measurement. There is a range of modalities available for data collection including: smartphone (handheld), tablet, IVR, and Internet. To retain the integrity of the different administration modalities of the DHP-18, an eDHP-18 can be administered using a combination of handheld devices and the Internet for self-administration, reading face-to face to the respondent and administration over the Internet. However, there is the requirement that sponsors provide evidence to support the comparability or measurement equivalence of the eDHP-18 to the paper-based version from which it has been adapted.

	The level of evidence to support the comparability or measurement equivalence of the ePRO to the paper-based PRO from which it has been adapted will vary in accordance with the magnitude of the modification and its effect on the content, format, and interpretation of the PRO items and scales. Guidelines suggest that the psychometric properties of the original measure will still hold for the ePRO version if only minor modifications have been carried out, and that cognitive debriefing and usability testing will likely suffice as the level of evaluation.

 In cases where substantial modifications have been made, establishing the measurement equivalence of the ePRO is likely to include full psychometric evaluation.

	Let us compare one question from the DHP-18 in paper format, and the electronic version on integrated handheld devices. Questions on both paper and electronic devices are the same but the response mechanics are different. Also, the electronic version requires that answers be complete before progressing to the subsequent question, improving data quality and compliance.

	When there is only a little change between paper and the electronic instrument, it will be shown, a cognitive debrief is required to demonstrate the similarities and differences between the visuals.

	While the reuse of validated questionnaires seems intuitive and practical, there remain some obstacles to transitioning questionnaires to electronic versions. Developers do not license screen shots of validated instruments and this makes it difficult for ePRO providers to provide fully reusable versions of questionnaires based on a published specification. Sponsors often regard validated instruments as private assets and a competitive advantage, and are reluctant to publish any studies done to establish the validity of such assets. Additionally, the compensation of the authors and copyright holders of the questionnaires necessitates licensing of copyright and other logistical matters.

	The virtue of providing validated instruments to the industry at large is certainly recognized, and academic societies, industry groups, and distribution channels are evolving to support this need. One such group which has recently formed is the ePRO Consortium which is working with the Critical Path Institute on this goal.

	Validation required to migrate from PRO to ePRO

	The level of validation depends on the degree to which the appearance, operation, and content may be changed. An ISPOR publication distinguishes small, medium, and large changes.

	Small changes are exemplified by simple alterations in instruction wording, such as asking the responder to select a response option by "tapping" a screen rather than by "drawing a circle" on the paper. Another example is changing the presentation from several questions on a page to one per screen.

	Medium changes include changing modes of presentation from one sensory channel to another such as reading questions and responses to listening to someone else read them, or introducing an operation such as scrolling a screen in order to view what would appear on a single page on paper.

	Large changes are those that affect the meaning of the questions or the content of the measure (additions, deletions).

	Simply putting a paper questionnaire on an electronic device with no other changes may need only some usability and cognitive testing to support suitability for use. The level of change dictates the type of validation work required, ranging from cognitive debriefing with target patient populations to equivalence studies between the paper and electronic versions of the instruments.

Conversion from paper to ePRO for an instrument designed to assess diabetes' impact on quality of life.

ePRO in Diabetes Studies

PRO and ePRO systems provide significant insight into what happens to patients with cancer as they experience the disease and undergo treatment. The data they collect can measure treatment side effects, drug effects, patients’ symptoms and functioning, quality of life, compliance with regimens, and toxicity endurance. The data also enable real time monitoring of adverse effects, whether or not standards for such effects have been established.

ePRO methods help capture measures of emotional distress in ways that preserve privacy and allow patients to reveal their feelings without concern for the potential impact their affliction may have on their medical team, family, or caretakers. Thus, the ePRO solutions can improve communication between patients and doctors, help monitor progression of the disease, and provide trending information revealing any response to treatment. Such data helps with predicting clinical endpoints such as hospitalization.

This article describes how ePRO technology serves oncology trials.

In oncology as in other areas, ePRO has two major advantages over paper-based systems: 
 1. Data are attributable and time-stamped. 
 2. Data are available in real time. 

Both advantages benefit physicians, trial teams, researchers, and scientific reviewers at regulatory authorities.

The unique nature of clinical research in oncology

Because cancer encompasses numerous kinds of malignancies with diverse causes, oncology clinical drug trials vary in intent, scope, protocol, and methodology. Many include training of proxies or caregivers as well as patients. Unlike other therapeutic areas, most oncology trials do not include placebo groups. 

Three examples of oncology trials using ePRO technology

 Multiple myeloma, for example, has been one of the more intractable forms of cancer, one for which there is as yet no cure. Various clinical drug trials are underway, employing ePRO to measure efficacy and safety.

One ongoing trial is a 55-location, single-arm, open-label study that began in March 2011 to study the effects of a drug developed to treat multiple myeloma.

The primary endpoint for the study is progression-free survival.

Secondary endpoints include:
 1.  Safety, as measured by adverse events
 2.  Overall survival
 3.  Incidence and duration of response to the drug being tested 
 4.  Response of patients who are given blood or bone marrow transplants
 5.  Time to a clinically significant progression of the disease

Patients use an eDiary at the clinical site, recording their answers to questionnaires developed by the International Myeloma Working Group and the European Group for Blood and Marrow Transplantation. 

A report on ClinicalTrials.gov, a service of the US National Institutes of Health, stated: According to a report, Comprehensive Patient Reported Outcomes (PRO), Management for Oncology Practice published in April 2010, “The use of PRO instruments is part of a general movement toward the idea that the patient, properly queried, is the best source of information about how he or she feels. The goal of using PRO measures is to provide better information to doctors and patients so that the best treatment for patients can be determined.” 

http://clinicaltrials.gov/ct2/show/NCT01108315

Patients in other oncology trials are using ePRO instruments at home. The objective is to reduce cancer patient’s sense of isolation and to capture directly from patients their subjective assessments and reports on behavior and medication use in real time. In some cases patients record their symptoms daily or twice a week.

By having patients record their data on a handheld eDiary, trial managers can access reports and charts of data in real time and closely monitor changes that might indicate concern for patient safety. All the ePRO data can be viewed in an online clinical patient data reporting system. If data were collected on paper diaries, data review and any analyses could not occur until the trial’s conclusion. Such paper trials do not easily accommodate adjustments in treatments, endpoints, or study design.

2. In the United Kingdom, one longitudinal study has shown that over time, patient-reported outcomes facilitated patient/doctor discussion and improved patients’ quality of life.  Further details and the sponsor’s name have been withheld for confidentially purposes.  However the soft benefit of advancing the patient/doctor relationship has been acknowledged as a benefit of patient reported outcomes:

Opportunities from ePROs at home and at the clinical visit frequently collected may

 Enhance the understanding of cancer burden and implications of interventions,

Clinicians and sponsors anticipate that harvesting PRO information can help advance the care of oncology patients.  

3. One two-arm study of a drug developed for opiate-induced constipation (OIC) began in March 2011. The study consists of two 12-week randomized, placebo-controlled efficacy studies with more than 600 patients in each arm.

In this case, the primary objective is to compare the efficacy of the drug treatment for constipation against a placebo. Secondarily, the study is comparing the effects of the drug with the placebo on daily signs and symptoms that are associated with OIC. Patients keep twice-daily eDiaries that record bowel movements as well as any discomfort associated with bowel-related symptoms.

The trial also has several long-term exploratory objectives, which include characterizing the pharmacokinetics of the trial drug and the covariate effect in the targeted disease population as well as collecting and storing DNA for future research into genetic variations that may influence response to the drug. 

Oncology questionnaires deployed on ePRO systems include:

 Functional Assessment of Cancer Therapy-Breast (FACT-B)

 Chemotherapy Convenience and Satisfaction Questionnaire (CCSQ)

 Functional Assessment of Cancer Therapy-Colorectal (FACT-C)

 Functional Assessment of Cancer Therapy-Lung (FACT-L)

 EORTC Multiple Myeloma Module (QLQ-MY20)

 The Functional Assessment of Cancer Therapy-Prostate (FACT-P)

 Functional Assessment of Cancer Therapy (FACT-G)

Many patients with cancer and other conditions suffer not only from their primary disease but from the side effects from treatment. One of the more troublesome side effects is the previously-mentioned OIC, a frequent result of the use of morphine and other long-term opiates to treat pain. Nearly half of patients taking opiates long term experience OIC. 

Regardless of whether the trial is sponsored by industry; teaching hospitals; associations; or government agencies, collecting the voice of the patient via ePRO systems has proven to deliver sensitive indications of changes in a patient’s condition whether the patients are in a facility or at home. ePRO benefits include:

 The data can help improve palliative care by ensuring that nurses have access to trends in key symptoms such as nausea, pain, constipation, and diarrhea as well as doses of medication.

 Physicians can get a better understanding of the burden of both cancer and the side effects of treatment by showing quantitative changes over time in graphs and tables.

 Patients find ePRO easier to use than paper. Software is intuitive, patients see screen images in their native languages, and for patients with fatigue, page turning and illumination are automated.  

 The burden on the site staff can be reduced because they produce and preserve electronic source records. With ePRO systems there is no need for study staff to re-enter patient data. 

 Study sponsors receive real-time information, so there is no need to wait until the end of the study for analysis. Dynamic trials and timely interventions are supported.

 Study sponsors have found it easier to meet regulatory guidelines. The system includes checks and constraints that prevent error, block shortcuts, and prevent fraud.

The following emerged as likely reasons for success [of oncology trials using ePRO]:

 Clear rationale for pre-specified endpoints

 Adequately powered trials to detect differences and clinically significant changes

 Developing an a priori statistical analysis plan including primary and subgroup analyses, dealing with missing data, pooling multiple-site data

 Establishing clinical versus statistical significance

The growing use of PRO instruments in oncology studies reflects acceptance that patients themselves are the best source of information about their symptoms, levels of pain, and quality of life. Leading scientists and practitioners realize that ePRO data are more accurate and accessible than paper-based diary and questionnaire data.With better information, physicians can provide more effective treatment, regulatory authorities have unbiased results they can trust, and industry is better able to plan development of new drugs. 

Perhaps the greatest beneficiaries are patients: a report entitled, “Comprehensive Patient Reported Outcomes (PRO) Management for Oncology Practice” published in August 2011 stated “…many cancer patients feel set adrift in having to self-manage treatment and illness-related symptoms at home, resulting in a sense of burden for the patient and the caregiver… The use of PRO instruments is part of a general movement toward the idea that the patient, properly queried, is the best source of information about how he or she feels.” 

1. Oncology Patient-Reported Claims: Maximizing the Chance for Success, 

http://www.ecancermedicalscience.com/view-article.asp?doi=10.3332/ecancer.2011.212&type=abstract, submitted 09052011

2. PowerPoint presentation by Kathleen Gondek, PhD from Bayer Pharmaceuticals Corporation, 

Christine Hall is Senior Marketing Manager at PHT Corporation.

Benefit from industry updates and case studies related to this article


Ensure Content Validity of PRO Concepts and Capture Patient Data with New Technology
May 7-8, 2012
Philadelphia, Pennsylvania


Christine Hall

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