By Laurie Meehan, Polaris Compliance Consultants, Inc.
In the clinical research industry, we’re always evaluating things. We evaluate drugs and biologics. We evaluate medical devices. We also evaluate research techniques. Yes, we try trials. We study studies. That’s what Pfizer was doing when it launched its REMOTE pilot trial in early 2011 – evaluating the effectiveness of a study in which patients participated remotely, without ever having to visit a study site. How would the results of the REMOTE study compare with those of a similar, completed, conventional study? Would this innovative research approach be validated?
There were plenty of good reasons for Pfizer to try to answer these questions. “Virtual” trials would make research participation possible for patients who live far from investigative sites, or for patients who have trouble moving about. Virtual trials may reduce patient withdrawal rates, as remote access would likely be more convenient and require less of a time commitment from patients. They also have the potential to save research dollars.
Results of the REMOTE trial
Despite its potential, within a year, the REMOTE trial was in jeopardy. In its trial announcement, Pfizer said it had planned to enroll 600 patients, but in March 2012 reported having trouble meeting that target. In May 2012, Pfizer terminated further enrollment, able to randomize only 18 patients into the study.
Disappointing? Yes. End of the story? Not at all.
Last week, Pfizer formally published the results of the REMOTE pilot in Contemporary Clinical Trials. They concluded “the efficacy observed was consistent with results from conventional trials.” (Detailed results from the ClinicalTrials.gov website can be found here.) Though enrollment was quite low, that REMOTE results were consistent with those of the conventional study is a positive outcome, crucial for the viability of virtual trials.
Pfizer further concluded that “with simplification of multi-step screening and testing, web-based trials or their component parts should provide a participant-friendly approach to many clinical trials.” The first part of the statement, the piece about “simplification,” comes from analyzing what went wrong with enrollment. The second part of the statement comes from observing what components worked well.
Characteristics of the REMOTE trial
What Went Wrong?
Through observation and patient feedback, Pfizer uncovered some of the operational factors that significantly contributed to the dismal enrollment. Identity verification had been conducted by asking a potential subject some facts from his/her personal history, such as the hospital in which the patient was born, the model of car the patient owned in 1997, the street on which the patient lived in 1985. Pfizer anticipated it would be able to validate the patient responses using publicly available sources. It turned out the necessary data was often publicly unavailable, leading to automatic exclusion. Also, the data entry software was unforgiving, and correcting mistakes was difficult. Lastly, a patient who successfully navigated the ID verification process would sometimes fail to proceed to the next step simply because confirmation email from Pfizer was blocked as SPAM. At least two of those issues can be easily fixed. (1) Data entry/interface software can be improved; ask any human factors expert. (2) Patients can be advised to add the appropriate domain name to their Safe Senders lists and email can be sent that is devoid of the characteristics SPAM filters love to hate.
What Went Well?
Answer #1: online video-based informed consent. Pfizer’s technique received positive feedback from both IRBs and federal regulators. The online format allowed consent to be standardized across sites, and subject understanding was verified using a quiz.
Answer #2: EDC tools (ePRO, online portal, lab reporting, direct IVRS interface). They allowed for real-time edit checking, study and subject compliance monitoring, and early access to safety signals. Pfizer observed a significant drop in queries per subject than is typical.
Both online video informed consent and the EDC tools with which Pfizer gained experience during the REMOTE pilot are the types of components, to which Pfizer referred in its final report, that could be used to enhance any study.
Pfizer plans to conduct another virtual trial, REMOTE 2.0, in Europe. They have an opportunity to fix the issues they encountered during the pilot as well as introduce some other patient-centric strategies. Pfizer plans to offer additional assistance to patients during the screening process and to engage patients’ primary care physicians who can be a familiar presence in what can otherwise seem a foreign process. They also plan to issue iPad-like communication devices to facilitate communication with patients who spend little time online.
Surely, all eyes will be on the progress of enrollment and on-going process of patient engagement. What else will REMOTE 2.0 teach us?
[Some of the preceding information comes from a June 2013 talk at the ACRON Symposium, given by Miguel Orris, then Senior Director of Clinical Sciences at Pfizer.]