[Inf 295] week 6 parul seth patient-reported outcomes as a source of evidence in off-label prescribing

Patient-reported Outcomes as a Source of Evidence in Off-Label Prescribing:Analysis of Data From

Jeana Frost, Sally Okun, Timothy Vaughan, James Heywood, and Paul Wicks

Presenter: Parul SethUniversity of California, IrvineINF 295 Topics In Health InformaticsNovember 6th, 2013

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Background: Patient-reported Outcomes (PROs)

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“The term "patient-reported outcomes (PRO)" is used to refer to a host of outcomes that can be provided only by the patient. Examples of these outcomes include symptom severity, perception of daily functioning, feelings of well being, global impressions of the impact of treatment on daily life, satisfaction with treatment, and health-related quality of life.”

Source: http://www.ispor.org/meetings/va0502/symposium.asp

Background: Off-label and On-label (FDA Approved)

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21% of all prescriptions are for off-label purposes

73% lacked scientific evidence underlying their use(Radley et al 2006)

Off-label prescribing: A source of innovation. But how to have supporting evidence for off-label uses of a drug?

Off-label Use in the News

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Source: http://www.usatoday.com/story/money/business/2013/11/04/johnson-and-johnson-fines-drug-marketing/3432955/

Problem

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Off-label prescribing although legal in USA can be done without supporting medical evidence.

Providers and patients may rely upon their own individual-level experience to inform clinical practice, which generates only anecdotal and unstructured data.

Patients may subject to unnecessary, ineffective, and even harmful treatments.

Clinical Trials for testing off-label use are rare, expensive and time consuming (costs US $15,700 for a phase 1 trial and over US $26,000 for a phase 3 trial per patient).

Problem

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Limitations of FDA guidance (2008), “Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices”

Trade-off between quality of scientific literature & informal acceptability benchmark

Need for counterbalancing evidence from industry- publication bias, significant vs. non-significant findings

Off-label medication is frequently the only option for “orphan conditions” or where there is no “approved treatment”.

Limited applicability of regulations, mostly to visible means of promotion.

Unlikely enforcement of guidance (not legally binding)

There is a need for evaluating a new use of a drug in an inexpensive and efficient manner.

Proposed Solution

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“A new source of evidence to evaluate off-label use: patient-reported outcomes entered via an online community.”

Patients, entering outcomes within an online community, could inform how drugs are working for off-label uses by expanding the available evidence base.

Online Community: Health 2.0

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Source: http://scienceroll.com/2013/05/01/healthcare-infographics-help-start-a-conversation/

Proposed Solution

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A new source of evidence to evaluate off-label use: patient-reported outcomes entered via an online community: Patients Like Me (PLM).

PROs

Structured Patient-reported Data

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200,000+ Patients

7721 Symptoms

“A tool for patients, researchers, and caregivers that helps users make treatment decisions, manage symptoms, and improve outcomes.”

Interactive treatment report from PLM can suggest usage patterns and effectiveness rates for drugs across different purposes.

Interactive Treatment Report

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Study Objective

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To examine the illustrative cases of Amitriptyline and Modafinil – drugs commonly used off-label across five PLM communities.

“Antidepressants like Amitriptyline (available since 1961) with one FDA approved purpose (depression) have been highlighted as an important target for future research into off-label drug use. (14 clinical trials involving amitriptyline on clinicaltrials.gov)”

“Modafinil (available since 1998) is a wakefulness-promoting agent for approved purposes related to sleep disorders, including narcolepsy, shift-work disorder, and obstructive sleep apnea.”

Methods

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Post hoc analysis of the prevalence of on-label versus off-label use, dosing, and perceived effectiveness and side effects for the medications.

Two drugs: Amitriptyline and Modafinil

Five condition based PLM communities with 53,928 members: MS (Multiple sclerosis), fibromyalgia/chronic fatigue syndrome, ALS (Amyotrophic lateral sclerosis), mood disorders (depression, bipolar disorder, and anxiety disorders), and Parkinson's disease

Results: Modafinil

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1948 treatment histories: 1316 described current treatment at the time of analysis

2% (1316/53928) of all members reported currently taking modafinil. Most prevalent use in MS community- 1565 reports for 17,820 members

(6%) Purposes were reported in 1755 of 1948 (90%) modafinil treatment

histories. Only 34 of 1755 (less than 1%) of members reported taking modafinil for an

approved purpose (narcolepsy and excessive daytime sleepiness resulting from sleep apnea)

Modafinil was most commonly used to treat purposes that fall within “general disorders and administration site conditions” (1277/1755, 73%) followed by “nervous system disorders” (415/1755, 24%).

726 treatment evaluations written about modafinil at time of analysis and 383 side-effect reports.

Most users (532/726, 72%) rated the effectiveness of modafinil in the highest response categories: either “major” or “moderate”

Results: Amitriptyline

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1394 treatment reports 2% (865/53928) of all members reported currently taking amitriptyline. Most prevalent use in ALS community- 228 of 4060 (6%) reported earlier use of

the drug, 178 of the 4060 (4%) currently taking the drug. Most common purpose in ALS was treating excess saliva (88 of 220 -40%).

Purposes were reported in 1197 of the 1394 (86%) amitriptyline treatment reports.

104 of 1197 reports (9%), patients reported taking amitriptyline for the approved use of depression

Most commonly, patients reported taking it for insomnia and other sleep problems (321/1197, 27%) or pain (197/1197, 17%)

270 side-effect reports, most common, feeling sleepy, dry mouth & weight gain. Most users (532/726, 72%) rated the effectiveness of modafinil in the highest

response categories: either “major” or “moderate” The effectiveness ratings for off-label purposes were higher than for

depression: 28 of the 70 (40%) respondents taking it for the prescribed purpose of depression rated it as having either a major or moderate efficacy in comparison to 273 of 520 (52%) taking it for off-label uses

Results

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Only less than 1% of nearly 2000 patients taking modafinil and 9% of nearly 1400 patients taking amitriptyline reported taking each drug for purposes approved by the FDA.

The effectiveness for off-label uses was reported to be as either higher than or comparable to approved indications.

Many patients used some of the most common side effects reported for amitriptyline, including sleepiness, as their purpose for taking the drug, such as the treatment of insomnia.

Conclusions

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Online communities like PatientsLikeMe, offer a unique real-time approach to understand utilization and performance of treatments across many conditions.

Offer ability to reach a large population of users at relatively little marginal cost.

Gain experiences directly from patients: researchers can elicit new types of data not recorded systematically through routine clinical practice.

New source of evidence about secondary uses and potentially identify targets for treatments to be studied systematically in traditional efficacy trials.

Internet offers a unique vehicle to collect vast quantities of data far more effectively than traditional studies permit.

Challenges & Limitations

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Information Bias: incomplete information reported by patients.

Lower-level of Confidence in the data reported

Unreported comorbidity and confounding (socio-economic status and health literacy).

Misrepresentation of identity: false identities

Developments @

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Tool for showing list of trials from ClinicalTrials.gov to the PLM community

References

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Frost, J, Okun, S, Vaughan, T, Heywood, J, Wicks, P. Patient-reported outcomes as a source of evidence in off-label prescribing: analysis of data from PatientsLikeMe. Journal of medical Internet research 13, 1 (2011), e6.

Janssens, A Cecile JW, and Peter Kraft. "Research conducted using data obtained through online communities: ethical implications of methodological limitations." PLoS medicine 9.10 (2012): e1001328.

All images have been searched and downloaded from Google Images

http://www.patientslikeme.com/ https://www.openresearchexchange.com/ http://www.patientslikeme.com/clinical_trials

Discussion

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