Wireless Transmission of Spirometric Measurements to ePRO Devices Used by Subjects with AsthmaStephen A. Raymond, PhDChief Scientific Officer and FounderPHT Corporation

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Relation to Session Objective“…Tools that can enhance the quality and reliability of data”

• Companies sponsoring clinical trials that rely on patient self-reported data for primary or secondary endpoints must be confident that such data are correct and trustworthy.

• Examples of self-reported data include symptom scores (e.g. peak expiratory flow, pain, nausea, sleep quality), patient behavior (e.g. medication consumption, vomiting, sleep time) and physiological measures from devices (e.g. physical activity, bodyweight).

• Research using paper methods to capture self-reported data from measuring devices has shown that subjects invent data, enter erroneous data, enter data that is illegible, incomplete or in an incorrect format, or, worse, provide no data at all (Ref 1-4).

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Spirometric Data QualityData Quality problems—An Example • Childhood asthma study done by G. Jonasson et. al. (Ref 3) • Subjects reported consuming medication from a metered dose

inhaler.– 200 doses – Instrumented to track actual consumption and compliance with the

dosing schedule. • All subjects reported high med compliance on paper diaries, • the measured compliance from the inhaler [200–No. of remaining

doses)/No. of prescribed doses] was:– Lower than reported, indicating that subjects faked data.– Most subjects faked data – some subjects invented almost all the data.

• Even those subjects with the worst measured compliance entered readings on their paper diaries for nearly all of the expected doses.

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Rationale for Wireless System

• Self-reported peak flow data are known to be inaccurate when entered in paper diaries

• Regulatory agencies recommend “electronic diaries” (Ref 5-6) “to validate the timing” of transcribed measurements and to ensure compliance calculations are “reliable”

• but any method that relies on the subjects to read and transcribe values also remains vulnerable to transcription errors and invented data.

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eDiary and Wireless PEFOption1. Wireless (short-range ~10 feet) radio link) Option 2. Manual Transcription

PEF, FEV1 from Meter to eDiary

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Field Experience in Trials

Methods: • Subjects were provided with an electronic

patient diary (eDiary), and a PEF meter• equipped with wireless technology that

automatically sends data to the eDiary. • Subjects were also given the option to

transcribe PEF readings manually into the eDiary, without the use of the wireless transfer feature.

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Field Experience in Trials

Methods, example 1: • 172 Subjects were provided with an electronic

patient diary (eDiary), and a PEF meter• Wireless, automatic transfer of data to the

eDiary was enabled for each subject. • Subjects were also given the option to transcribe

PEF readings manually into the eDiary, without the use of the wireless transfer feature.

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Example 1: results

12,195 individual PEF score measurements23 European Investigative Sites

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Example 1: the “manual” choice

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Example 1: Sites matter

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Data Quality--Completions

• Expectation: During participation (Assignment of the eDiary until the last eDiary report transmitted) – morning and evening diary were expected each day

• Completions: Most subjects conformed. Median percent completion compliance: – For the morning diary was 97.96% – For the evening diary 99.07%.

• subjects in the range of 95-100%:– 123 for the morning diary– 114 for the evening diary– Only four subjects had completion compliances for either diary at

70% or less.

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Conclusions-Example 1• A portable electronic monitoring system to prevent false self-

reported PEF data by using wireless uploads to an eDiary was feasible for a multicenter, multinational clinical investigation.

• More than 85% of the PEF data automatically – where the PEF value, time of capture could NOT be invented, manually

altered, or erroneously transcribed.• Subjects completed almost every report that was expected even

though no report could be entered retrospectively. – Reports could be completed only during 6 hour windows in the morning

and evening.– Constraining the availability of eDiary reports for completion did not

unduly reduce the number of reports that subjects completed.• Choice of manual vs automatic transfer of PEF data depended on

site.

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Completions: Field ExperienceAVERAGE Completion Compliance for 3,365 Subjects

IndicationSubjects Sites

eSense PiKo

Received Daily Diaries

Expected Daily Diaries

Completion Compliance

1 Asthma 1102 147 No 316,420 398,296 79%

2 Asthma 172 18 Yes 12,195 12,826 95%

3 Asthma 600 72 No 38,416 39,932 97%

4 Asthma 100 22 No 7,996 8,266 97%

5 COPD 100 8 Yes 8,460 8,892 95%

6 COPD 660 76 Yes 120,818 127,261 95%

7 COPD 450 67 Yes 31,658 35,602 89%

8* Asthma 96 of 320 33 0f 45 Yes 5,332 5,572 96%

9* COPD 62 of 83 56 of 336 No 1,118 1,508 74%

10* COPD 23 of 33 20 of 558 Yes 673 718 94%

*Trials still recruiting the number of subjects enrolled are shown relative to the number of planned randomized subjects.

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Conclusions-Data Quality

• Wireless Spirometric Devices– Yield data of validated quality – Prevent many known data quality problems– Are feasible for subjects to use– Add objective information to eDiary data– Do not diminish the completion compliance for

ePRO data

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References1. Verschelden P., A. Cartier, J. L’Archevêque, C. Trudeau, J. L. Malo. Compliance with and accuracy

of daily self-assessment of peak expiratory flows (PEF) in asthmatic subjects over a three month period. 1996. Eur Respir J. May;9(5):880-5.

2. Milgrom H., B. Bender, L. Ackerson, P. Bowry, B. Smith, C. Rand. Noncompliance and treatmentfailure in children with asthma. 1996. J Allergy Clin Immunol. Dec;98(6 Pt 1):1051-7.

3. Jónasson G., K. H. Carlsen, A. Sødal, C. Jonasson, P. Mowinckel. Patient compliance in a clinicaltrial with inhaled budesonide in children with mild asthma. 1999. Eur Respir J. Jul;14(1):150-4.

4. Kamps A.W., R. J. Roorda, P. L. Brand. Peak flow diaries in childhood asthma are unreliable.2001. Thorax. Mar;56(3):180-2.

5. Note for guidance on the clinical investigation of medicinal products in the treatment of asthma,EMEA CPMP/EWP/2922/01, 2002

6. Guideline on clinical investigation of steroid contraceptives in women, EMEA CPMP/EWP/519/98Rev 1, 2005

7. Raymond SA, Blackadar T, Oueida W, Ohlenbusch NE. Preventing false spirometry values andinvalid symptom scores in respiratory clinical trials. The Journal of Allergy and Clinical Immunology, Supplement Feb. 2004:113(2):S277

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