Patient-reported outcomes validated in phase 3 clinical trials: a targeted literature review

Figures & data

Table 1. MEDLINE database search strategy.

Search #	Algorithm
1. Instrument terms	Exp Surveys and Questionnaires/ OR Exp Self-report/ OR Exp Patient reported outcome measures OR Exp patient outcome assessment/ OR (Questionnaire^a or Scale^a or Instrument^a or diaries or diary or Survey^a or patient-report^a or self-administ^a or self-report^a or Tool^a or Index or Inventory or checklist^a or PROMS).ab,ti.
2. Validation terms	exp Psychometrics/ OR exp Validation study/ OR exp validation studies as topic/ OR exp Reproducibility of results/ OR (Validation or validity or responsiveness or ability to detect change or minim^a important difference^a or MID or minim^a clinical^a important difference^a or MCID or reliability or internal consistency or Cronbach or know-group^a or test-retest or inter-rater or inter-observer or intra-rater or intra-observer).ab,ti.
3. Study terms	(Phase III or phase 3).ab,ti.
Limits	Abstract, English language, Human, Last 15 years, Publication type: Clinical trial, phase III or Validation study.
Final algorithm	#1 AND #2 AND #3 AND Limits

Abbreviations. MCID, minimal clinically important difference; MID, minimal important difference; PROMS, patient-reported outcome measures.

Exp Term/, search in Mesh-Tree exploded; ab.ti., search performed in title and abstract field.

^aUnlimited truncation, any word that begins with the term will be retrieved.

Figure 1. PRISMA flow diagram for the selection process of the references retrieved by the MEDLINE search. Abbreviations. COA, clinical outcome assessments; PRO, patient reported outcomes

Figure 2. Labelling claims flow diagram. ^aData on study design, therapeutic indication, and psychometric assessment results extracted from 21 studies for all the 20 instruments validated in the publications. Abbreviations. OMDQ, Oral Mucositis Daily Questionnaire; PEP, Premature Ejaculation Profile; PDQ, Peyronie’s Disease Questionnaire; PRO, patient reported outcome. WPS-RA, Rheumatoid arthritis-specific Work Productivity Survey; VVSymQ, Varicose Veins Symptoms Questionnaire.

Table 2. PROs with label claim.

PRO instrument	Drug brand name	Status	Regulatory agency	Therapeutic indication	Study summary	Claim approval date	Concept of interest	Endpoint	Claim
OMDQ Oral Mucositis Daily Questionnaire	Kepivance	Withdrawn	EMA	Mucositis	Study 2	10/25/2005	Mouth and throat soreness	Secondary	Kepivance [Palifermin] treated patients demonstrated significant benefits in patient-reported outcomes of mouth and throat soreness and its impact on swallowing, drinking, eating, and talking
PDQ Peyronie’s Disease Questionnaire	Xiaflex	Approved	FDA	Penile induration	Studies 1 and 2	12/06/2013	Symptom bother	Primary	Xiaflex significantly reduced patient-reported bother associated with Peyronie’s disease compared with placebo. The reduction in the bother domain score was numerically similar between patient groups stratified by degree of baseline curvature deformity (30–60 degrees and 61–90 degrees).
	Xiapex	Withdrawn	EMA	Penile induration	AUX-CC-803 and AUX-CC-804	02/02/2015	Erectile function	Primary	Xiapex significantly reduced patient-reported bother associated with Peyronie’s disease compared with placebo. The reduction in the bother domain score was numerically similar between patient groups stratified by degree of baseline curvature deformity (30–60 degrees and 61–90 degrees). Through the 5-year follow-up period, subjects demonstrated an improvement in penile curvature and in PDQ bother compared with the last observed value from the previous phase 3 studies.
					Study AUX-CC-806	05/26/2016	Erectile function	Primary
					Long-term follow-up study AUX-CC-810	05/29/2019	Erectile function	Not specified
PEP Premature Ejaculation Profile	Fortacin	Approved	EMA	Premature ejaculation	Study 1	11/15/2013	Ejaculatory control and difficulty, sexual satisfaction, distress	Secondary	The PEP scores followed a similar pattern of improvement to the IELT and IPE scores. For all of the three-monthly assessments completed by the subjects, there was a significant difference between Fortacin/Senstend and placebo (p < .0001).
	Senstend	Approved	EMA	Premature ejaculation	Study 1	11/14/2019	Ejaculatory control and difficulty, sexual satisfaction, distress	Not specified
VVSymQ Varicose Veins Symptoms Questionnaire	Varithena	Approved	FDA	Varicose veins	Vanish 1 and Vanish 2	11/25/2013	Symptom Improvement	Primary	For both VANISH-1 and VANISH-2, treatment with 1.0% Varithena was superior to placebo in improving symptoms as measured by VVSymQ, when either a duration or an intensity scale was used to measure patients’ symptoms
WPS-RA Rheumatoid arthritis-specific Work Productivity Survey	Cimzia	Approved	EMA	Spondylitis, ankylosing	Study AS001	10/18/2013	Productivity	Secondary	Cimzia-treated patients reported significant improvements in axial spondyloarthritis-related productivity at work and within household, as reported by the Work Productivity Survey as compared to placebo. For patients remaining in the study, improvements in all afore-mentioned outcomes were largely maintained through Week 204
				Arthritis, psoriatic	Study PsA001	11/25/2013	Productivity	Secondary	Cimzia statistically improved ACR component response rates and psoriatic arthritis-related productivity at work and within household, as reported by the Work Productivity Survey compared to placebo. Improvements in all afore-mentioned outcomes were maintained through Week 216.

Abbreviations. ACR, American College of Rheumatology; EMA, European Medicines Agency; FDA, US Food and Drug Administration; PRO, patient-reported outcomes.

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