PHT comments on FDA's PRO Final Guidance

PHT Corporation, the leading provider of ePRO (electronic patient reported outcome) solutions used in more than 400 clinical trials worldwide, commented on the FDA’s recent release of a final guidance almost four years following a Draft Guidance on the topic. The Final Guidance is entitled: Guidance for Industry, Patient-Reported Outcomes Measures: Use in Medical Product Development to Support Labeling Claims.

“When the amount of missing data becomes large, study results can be inconclusive.”

This PRO Final Guidance announced earlier this month helps those who develop medical products understand how to include the patient viewpoint in the clinical trials that support market authorization for those products. The guidance shows FDA understands the pivotal role of PRO measures in establishing clinical benefit, and is aimed at ensuring sponsors collect PRO data using good science.

Some problems such as pain, anxiety, headache, and functional capabilities are best known by patients and are difficult to assess by observation or impossible to measure objectively. ePRO systems are significantly more reliable than paper diaries because of key aspects including data quality controls, time-stamping and branching logic. FDA has become increasingly aware of the higher data quality that electronic methods can provide, and several sections of the FDA’s Final Guidance are devoted to ePRO in clinical research. The ePRO considerations are developed more fully in this final Guidance than in the 2006 Draft Version. For example, new to this version of the Guidance is a cogent list of special considerations that sponsors should undertake when using ePRO.

PHT President and CEO Phil Lee said, “PHT is uniquely qualified to provide clinical trial sponsors with an ePRO system that meets regulatory expectations as outlined in this guidance. Furthermore, our unmatched trial experience and familiarity with converting and or developing ePRO instruments allows us to help sponsors obtain results that regulatory scientists will trust.”

PHT commented on specific sections of the draft guidance during the review period. The final Guidance notes that trial sponsors will need to take steps to assure that subjects complete scheduled diary reports when they are supposed to do so, and are not doing them in a batch in the parking lot just before a clinic visit.

1. Data Collection Method and Instrument Administration Mode (Pages 8-9)

“If a patient diary or some other form of unsupervised data entry is used, we plan to review the clinical trial protocol to determine what steps are taken to ensure that patients make entries according to the clinical trial design and not, for example, just before a clinic visit when their reports will be collected.”

Unlike paper diaries, PHT ePRO solutions both at the subject’s home and at the site solve this problem. They use restricted time response windows to prevent unplanned, prospective, retrospective and other non-compliant data entry; batch diary entry; or, forward filling. In addition, reminder alarms alert patients when a diary is due and PHT ensures that system timestamps are accurate and trustworthy.

2. Patient-Level Missing Data (Page 29)

“When the amount of missing data becomes large, study results can be inconclusive.”

The FDA had multiple concerns over incomplete or missing data. PHT’s LogPad® System and SitePad® Tablet provide more evaluable data than paper by collecting only complete, legible and logical reports. LogPad users are not allowed to transmit diaries until all appropriate items have been answered. In addition, PHT’s StudyWorks™ portal helps sites and sponsors carefully monitor patient progress between visits, resulting in fewer subject drop-outs and reducing the incidence of missing patient reported data.

3. Respondent Burden (Page 18)

“The degree of respondent burden that is tolerable for instruments in clinical trials depends on the frequency and timing of PRO assessments in a protocol and on patient cognition, illness severity, or treatment toxicity. For example, if the questionnaire contains instructions to skip one or more questions based on response to a previous question, respondents may fail to understand what to do and make errors in responding or find the assessment too complicated to complete. Sponsors should consider missing data and the refusal rate as possible indications of inappropriate respondent burden or inappropriate items or response options.”

The FDA does not want sponsors to place undue burden on patients. The LogPad and SitePad minimize respondent burden with features that make even complicated diaries simple for patient populations of all ages. Unique PHT eDiary features include simple touchscreen data entry, graphical data collection elements, front-end edit checks, automated scheduling, and programmed screen sequence controls that make data collection simple and clear for patients.

PHT will be sharing an analysis of the PRO Guidance and what it means for sponsors collecting PRO and ePRO data through a series of targeted educational programs beginning in January 2010. For more details on these events, please review www.phtcorp.com.