Study to Estimate the Burden of Herpes Zoster (HZ) and Post-herpetic Neuralgia (PHN) in Italy

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01772160
• Collaborator: (none)
• Enrollment: 395
• Locations: 43
• Actual Duration (Months): 43.3
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to collect data on the incidence, complications, economic burden and impact on the quality of life in adults aged ≥ 50 years with HZ disease in Italy.

Condition or Disease	Intervention/Treatment	Phase
Herpes Zoster; Herpes Zoster Vaccine	Other: Data collection

Detailed Description

The surveillance/recruitment period will take approximately 2 years and once the enrolment of HZ patients has ended, the study will continue for a maximum of 9 months to allow for completion of the follow-up of potential PHN cases.

The data will be captured at protocol specified time-points based on the time of enrolment of each subject.

Study Design

• Study Type: Observational
• Actual Enrollment: 395 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Population Based Surveillance to Estimate the Burden of Herpes Zoster and Post-herpetic Neuralgia in Italy
• Actual Study Start Date: Feb 26, 2013
• Actual Primary Completion Date: Oct 5, 2016
• Actual Study Completion Date: Oct 5, 2016

Arms and Interventions

Arm	Intervention/Treatment
Herpes Zoster Group Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.	Other: Data collection; HZ/PHN booklet, HZ/PHN file and logbook. HZ/PHN booklet will be completed by the patient and the HZ/PHN file and logbook will be completed by the participating general practitioner.

Outcome Measures

Primary Outcome Measures

1. Overall Incidence Rate of Herpes Zoster (HZ) Cases, by Age and Gender [Day 0 to 2 years]

   A case of HZ was defined as new unilateral pain (broadly defined to include allodynia and pruritus) accompanied by unilateral rash and no alternative diagnosis. Age ranges were 50-54, 55-59, 60-64, 65-69, 70-74, 75-79 and greater than or equal to (≥) 80 years. The incidence rate was expressed as the number of HZ cases per (/) 1000 person-years.

Secondary Outcome Measures

1. Percentage of Postherpetic Neuralgia (PHN) Cases Among HZ, Overall [At Day 90, 180 and 270 after onset of HZ]

   PHN persistence refers to pain occurring or persisting from Day 90 to Day 270 after the rash onset. PHN was assessed via the Zoster Pain Inventory (ZBPI) questionnaire, which includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'.

2. General Medical History of Cases With HZ, Overall [Between Day 0 and Day 270.]

   General medical history focused on characteristics such as patient pre-existing condition and diseases (local trauma, diabetes mellitus, liver disease, alcoholism, renal failure/dialysis, emotional problems, stress or depression, blood malignancy, solid malignancy, hematopoetic cell/ bone marrow transplant, solid organ transplantation, HIV infection, hepatitis C under active therapy, autoimmune disease active and under therapy, other).

3. Other General Medical History Characteristics for HZ Cases, Overall [Between Day 0 and Day 270.]

   Other general medical history characteristics referred to arterial problems, cerebral problems, gastric problems, gastric problems, prostate problems (arterial hypertension and allergic rhinitis, arterial hypertension and pacemaker, arteriopathy and past nun-Hodgkin lymphoma, atrial fibrillation, bronchopathy, cerebral thrombosis, cholecyst, chronic cerebral ischemia, chronic leukemia, chronic obstructive pulmonary disease, epilepsy, gastric lymphoma, gastropathy, hypertension, hypertension and hypothyroidism after surgery, hypertension dyslipidemia and hyperthyroidism, hypothyroidism hypertension, polycythaemia, polycythaemia from 10 years, prostate neoplasm, prostate oral anticoagulant therapy cardiopathy, prostatic cancer, right feet arthralgia, thrombocytopenia, vasculopathy chronic brain).

4. Clinical Information of Cases With HZ, Overall [Between Day 0 and Day 270]

   Clinical information of HZ cases referred to experience of any symptoms before rash, actual symptoms before rash (SBR), any complications at initial visit.

5. Complications Related to HZ Cases, Overall [Between Day 0 and Day 270]

   HZ related complications refer to cutaneous complications (Varicella Zoster Virus [VZV] dissemination, Bacterial superinfection), ocular (Loss of corneal sensation, Keratitis, Scleritis, Uveitis, Iridocyclitis), neurological (Meningo-encephalitis, Cranial nerve palsies, Peripheral nerve palsies, Ramsay-Hunt syndrome, Persistent HZ-related Pain), visceral [Neural extension of VZV infection (bronchitis, esophagitis,cystitis), VZV dissemination (pneumonia, arthritis, hepatitis] and other.

6. Other Complications Related to HZ Cases, Overall [Between Day 0 and Day 270]

   HZ related other complications refer to axillary lympagenopathy, burning sensation, hypoacusis, itching and rectum pain.

7. Direct Medical Costs, Direct Non-medical Costs and Indirect Costs [Up to Day 90]

   Cost data related to HZ included medication, procedures and referral to hospital/specialist for direct medical costs, transport for direct non-medical costs and missed time from work, sick certificate for the indirect costs.

8. Worst Pain Assessment in HZ Subjects [At Day 90]

   The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. the ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.

9. Average Pain Assessment in HZ Subjects [At Day 90]

   The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. the ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.

10. Impact of HZ on Quality of Life as Assessed by the Zoster Pain Inventory [At Day 0, 15, 30, 60, 90]

    PHN persistence refers to pain occurring or persisting between 90-270 days after the rash onset. PHN was assessed via the Zoster Pain Inventory (ZBPI) questionnaire, which includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'.

11. Impact of HZ on Quality of Life as Assessed by the EuroQoL-Five Digits [At Day 0, 15, 30, 60, 90]

    EuroQoL-Five Digits (EQ-5D) is a standardised instrument for use as a measure of health outcome and is designed for self-completion by respondents. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index/scale goes from 0 (worst health state) to 1 (perfect health state).

12. PHN Direct Medical Costs, Direct Non-medical Costs and Indirect Costs by Payer/Societal Perspective [Between Day 90 and Day 270]

    Cost data related to HZ included medication, procedures and referral to hospital/specialist for direct medical costs, transport for direct non-medical costs and missed time from work, sick certificate for the indirect costs.

13. Worst Pain Assessment in PHN Subjects [At Day 90]

    The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. the ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.

14. Average Pain Assessment in PHN Subjects [At Day 90]

    The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. The ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.

15. Impact of PHN on Quality of Life as Assessed by the Zoster Pain Inventory [At Day 0, 15, 30, 60, 90]

    PHN persistence refers to pain occurring or persisting between 90-270 days after the rash onset. PHN was assessed via the Zoster Pain Inventory (ZBPI) questionnaire, which includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'.

16. Impact of PHN on Quality of Life as Assessed by the EuroQoL-Five Digits [At Day 0, 15, 30, 60, 90]

    EuroQoL-Five Digits (EQ-5D) is a standardised instrument for use as a measure of health outcome and is designed for self-completion by respondents. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was 0 (worst health state) to 1 (best health state).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A male or female ≥ 50 years of age at the time of study enrolment presenting with acute HZ.

• HZ diagnosis for this HZ episode:

• Is his/her first outpatient diagnosis (i.e. initial consultation), OR

• Took place at another site/centre (e.g. emergency room or Dermatologist/Specialist practice) provided the HZ diagnosis is not more than 7 days before the initial visit for the present study (i.e. secondary consultation).

• Written informed consent obtained from the patient.

• Ability to comply with study procedures.

Exclusion Criteria:

• Patient participating in another clinical study (participation in another observational, non-interventional trial is allowed).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Napoli	Campania	Italy	80125
2	GSK Investigational Site	Napoli	Campania	Italy	80126
3	GSK Investigational Site	Roma	Lazio	Italy	00141
4	GSK Investigational Site	Roma	Lazio	Italy	00142
5	GSK Investigational Site	Roma	Lazio	Italy	00144
6	GSK Investigational Site	Roma	Lazio	Italy	00162
7	GSK Investigational Site	Roma	Lazio	Italy	00176
8	GSK Investigational Site	Roma	Lazio	Italy	00197
9	GSK Investigational Site	Angera (VA)	Lombardia	Italy
10	GSK Investigational Site	Arcisate (VA)	Lombardia	Italy	21051
11	GSK Investigational Site	Comerio (VA)	Lombardia	Italy	21020
12	GSK Investigational Site	Fagnano Olona (VA)	Lombardia	Italy	21054
13	GSK Investigational Site	Ghirla Valganna (VA)	Lombardia	Italy	21030
14	GSK Investigational Site	Induno Olona (VA)	Lombardia	Italy	21040
15	GSK Investigational Site	Sesto Calende (VA)	Lombardia	Italy	21018
16	GSK Investigational Site	Solbiate Olona (VA)	Lombardia	Italy	21052
17	GSK Investigational Site	Varese	Lombardia	Italy	21100
18	GSK Investigational Site	Alessandria	Piemonte	Italy	15121
19	GSK Investigational Site	Frugarolo (AL)	Piemonte	Italy	15065
20	GSK Investigational Site	Oviglio (AL)	Piemonte	Italy	15026
21	GSK Investigational Site	Sale (AL)	Piemonte	Italy	15045
22	GSK Investigational Site	Villalvernia (AL)	Piemonte	Italy	15050
23	GSK Investigational Site	Cavallino (LE)	Puglia	Italy	73020
24	GSK Investigational Site	Copertino (LE)	Puglia	Italy	73043
25	GSK Investigational Site	Cutrofiano (LE)	Puglia	Italy	73020
26	GSK Investigational Site	Galatina (LE)	Puglia	Italy	73013
27	GSK Investigational Site	Montesano S. (LE)	Puglia	Italy	73035
28	GSK Investigational Site	Parabita (LE)	Puglia	Italy	73052
29	GSK Investigational Site	Specchia (LE)	Puglia	Italy	73040
30	GSK Investigational Site	Arcidosso (GR)	Toscana	Italy	58031
31	GSK Investigational Site	Arezzo	Toscana	Italy	52100
32	GSK Investigational Site	Civitella Paganico (GR)	Toscana	Italy	58045
33	GSK Investigational Site	Follonica (GR)	Toscana	Italy	58022
34	GSK Investigational Site	Grosseto	Toscana	Italy	58100
35	GSK Investigational Site	Lucignano (AR)	Toscana	Italy	52046
36	GSK Investigational Site	Orbetello (GR)	Toscana	Italy	58015
37	GSK Investigational Site	Sassofortino (GR)	Toscana	Italy	58029
38	GSK Investigational Site	Perugia	Umbria	Italy	06125
39	GSK Investigational Site	Perugia	Umbria	Italy	06126
40	GSK Investigational Site	Perugia	Umbria	Italy
41	GSK Investigational Site	Ripa (PG)	Umbria	Italy	06134
42	GSK Investigational Site	Alessano (LE)		Italy
43	GSK Investigational Site	Rome		Italy	00144

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

• Salvetti A, Ferrari V, Garofalo R, Gazzaniga P, Guerroni A, Metrucci A, Sessa A, Severi ML, Nati G, Ruggeri M, Rossi A, Cappellari L, Gopala K, Tosatto R, Simone B. Incidence of herpes zoster and postherpetic neuralgia in Italian adults aged ≥50 years: A prospective study. Prev Med Rep. 2019 Apr 24;14:100882. doi: 10.1016/j.pmedr.2019.100882. eCollection 2019 Jun.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01772160
• Other Study ID Numbers: 116208
• First Posted: Jan 21, 2013
• Last Update Posted: May 22, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Adults; Italy; Herpes Zoster; Complications; Quality of life; Surveillance; Burden; Cost; Incidence
• Additional relevant MeSH terms: Herpes Simplex; Herpes Zoster; Neuralgia; Neuralgia, Postherpetic

Study Results

Participant Flow

Pre-assignment Detail	Out of 395 subjects originally enrolled in this study, 1 subject was excluded due to protocol violation, hence only 394 were included in the Total Cohort.

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Period Title: Overall Study
STARTED	394
COMPLETED	346
NOT COMPLETED	48

Baseline Characteristics

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Overall Participants	394
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	69.3 (11.0)
Sex: Female, Male (Count of Participants)
Female	238 60.4%
Male	156 39.6%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Overall Incidence Rate of Herpes Zoster (HZ) Cases, by Age and Gender
Description	A case of HZ was defined as new unilateral pain (broadly defined to include allodynia and pruritus) accompanied by unilateral rash and no alternative diagnosis. Age ranges were 50-54, 55-59, 60-64, 65-69, 70-74, 75-79 and greater than or equal to (≥) 80 years. The incidence rate was expressed as the number of HZ cases per (/) 1000 person-years.
Time Frame	Day 0 to 2 years

Outcome Measure Data

Analysis Population Description

The analysis was performed on the HZ cases occurring in the total population covered by the participating general practitioners (GPs).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	721
Female, 50-54	5.19
Female, 55-59	6.29
Female, 60-64	5.00
Female, 65-69	9.19
Female, 70-74	7.51
Female, 75-79	10.72
Female, ≥ 80	7.06
Male, 50-54	1.71
Male, 55-59	2.91
Male, 60-64	4.35
Male, 65-69	8.95
Male, 70-74	9.33
Male, 75-79	7.18
Male, ≥ 80	7.20
Overall incidence of HZ cases	6.46

2. Secondary Outcome

Title	Percentage of Postherpetic Neuralgia (PHN) Cases Among HZ, Overall
Description	PHN persistence refers to pain occurring or persisting from Day 90 to Day 270 after the rash onset. PHN was assessed via the Zoster Pain Inventory (ZBPI) questionnaire, which includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'.
Time Frame	At Day 90, 180 and 270 after onset of HZ

Outcome Measure Data

Analysis Population Description

The analysis was performed on the HZ cases (with completed questionnaires up to Day 270) occurring in the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	343
Overall PHN cases, Day 90	11.66
Overall PHN cases, Day 180	42.86
Overall PHN cases, Day 270	75.00

3. Secondary Outcome

Title	General Medical History of Cases With HZ, Overall
Description	General medical history focused on characteristics such as patient pre-existing condition and diseases (local trauma, diabetes mellitus, liver disease, alcoholism, renal failure/dialysis, emotional problems, stress or depression, blood malignancy, solid malignancy, hematopoetic cell/ bone marrow transplant, solid organ transplantation, HIV infection, hepatitis C under active therapy, autoimmune disease active and under therapy, other).
Time Frame	Between Day 0 and Day 270.

Outcome Measure Data

Analysis Population Description

The analysis was performed on the HZ cases occurring in the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	391
Pre-existing condition, Yes	32.74
Pre-existing condition, No	67.26
Pre-existing condition, Missing Confirmed	0.00
Local Trauma	3.91
Diabetes mellitus	35.94
Liver disease	4.69
Alcoholism	2.34
Renal failure/dialysis	7.03
Emotional problems, stress or depression	32.03
Blood malignancy	0.78
Solid malignancy	3.91
Hematopoetic cell/ bone marrow transplant	0.00
Solid organ transplantation	0.78
HIV infection	0.78
Hepatitis C under active therapy	0.78
Autoimmune disease active and under therapy	5.47
Other	25.00

4. Secondary Outcome

Title	Other General Medical History Characteristics for HZ Cases, Overall
Description	Other general medical history characteristics referred to arterial problems, cerebral problems, gastric problems, gastric problems, prostate problems (arterial hypertension and allergic rhinitis, arterial hypertension and pacemaker, arteriopathy and past nun-Hodgkin lymphoma, atrial fibrillation, bronchopathy, cerebral thrombosis, cholecyst, chronic cerebral ischemia, chronic leukemia, chronic obstructive pulmonary disease, epilepsy, gastric lymphoma, gastropathy, hypertension, hypertension and hypothyroidism after surgery, hypertension dyslipidemia and hyperthyroidism, hypothyroidism hypertension, polycythaemia, polycythaemia from 10 years, prostate neoplasm, prostate oral anticoagulant therapy cardiopathy, prostatic cancer, right feet arthralgia, thrombocytopenia, vasculopathy chronic brain).
Time Frame	Between Day 0 and Day 270.

Outcome Measure Data

Analysis Population Description

The analysis was performed on the HZ cases occurring in the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	32
Arterial hypertension and allergic rhinitis	3.13
Arterial hypertension and pacemaker	3.13
Arteriopathy and past non-Hodgkin lymphoma	3.13
Atrial fibrillation	3.13
Bronchopathy	3.13
Cerebral thrombosis	3.13
Cholecyst	3.13
Chronic cerebral ischemia	3.13
Chronic leukemia	3.13
Chronic obstructive pulmonary disease	3.13
Epilepsy	3.13
Gastric lymphoma	3.13
Gastropathy	3.13
Hypertension	25.00
Hypertension and hypothyroidism after surgery	3.13
Hypertension dyslipidemia and hyperthyroidism	3.13
Hypothyroidism hypertension	3.13
Polycythaemia	3.13
Polycythaemia from 10 years	3.13
Prostate neoplasm	3.13
Prostate oral anticoagulant therapy cardiopathy	3.13
Prostatic cancer	3.13
Right feet arthralgia	3.13
Thrombocytopenia	3.13
Vasculopathy chronic brain	3.13

5. Secondary Outcome

Title	Clinical Information of Cases With HZ, Overall
Description	Clinical information of HZ cases referred to experience of any symptoms before rash, actual symptoms before rash (SBR), any complications at initial visit.
Time Frame	Between Day 0 and Day 270

Outcome Measure Data

Analysis Population Description

The analysis was performed on the HZ cases occurring in the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	391
Any symptoms before rash, Yes	73.66
Any symptoms before rash, No	26.34
SBR, Prodromal pain	82.64
SBR, Fever	5.90
SBR, Malaise	29.17
SBR, Other:Ailment to the touch	0.35
SBR, Other:Burning sensation	3.13
SBR, Other:Dysesthesia	0.35
SBR, Other:Fever sensation	0.35
SBR, Other:Itching feeling of internal heat	0.35
SBR, Other:Itching	6.25
SBR, Other:Paresthesia	0.35
SBR, Other:Pain in right eyelid	0.35
SBR, Other:Pain in upper arms	0.35
SBR, Other:Sweating	0.00
Any complications at initial visit, Yes	16.62
Any complications at initial visit, No	83.38

6. Secondary Outcome

Title	Complications Related to HZ Cases, Overall
Description	HZ related complications refer to cutaneous complications (Varicella Zoster Virus [VZV] dissemination, Bacterial superinfection), ocular (Loss of corneal sensation, Keratitis, Scleritis, Uveitis, Iridocyclitis), neurological (Meningo-encephalitis, Cranial nerve palsies, Peripheral nerve palsies, Ramsay-Hunt syndrome, Persistent HZ-related Pain), visceral [Neural extension of VZV infection (bronchitis, esophagitis,cystitis), VZV dissemination (pneumonia, arthritis, hepatitis] and other.
Time Frame	Between Day 0 and Day 270

Outcome Measure Data

Analysis Population Description

The analysis was performed on the HZ cases occurring in the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	65
VZV dissemination	44.62
Bacterial superinfection	7.69
Loss of corneal sensation	0.00
Keratitis	10.77
Scleritis	0.00
Uveitis	4.62
Iridocyclitis	1.54
Meningo-encephalitis	0.00
Cranial nerve palsies	3.08
Peripheral nerve palsies	0.00
Ramsay-Hunt syndrome	0.00
Persistent HZ-related Pain	64.62
Neural extension of VZV infection	0.00
Pneumonia, arthritis, hepatitis	1.54
Other	7.69

7. Secondary Outcome

Title	Other Complications Related to HZ Cases, Overall
Description	HZ related other complications refer to axillary lympagenopathy, burning sensation, hypoacusis, itching and rectum pain.
Time Frame	Between Day 0 and Day 270

Outcome Measure Data

Analysis Population Description

The analysis was performed on the HZ cases occurring in the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	5
Axillary lymphadenopathy	20.00
Burning sensation	20.00
Hypoacusis	20.00
Itching	20.00
Rectum pain	20.00

8. Secondary Outcome

Title	Direct Medical Costs, Direct Non-medical Costs and Indirect Costs
Description	Cost data related to HZ included medication, procedures and referral to hospital/specialist for direct medical costs, transport for direct non-medical costs and missed time from work, sick certificate for the indirect costs.
Time Frame	Up to Day 90

Outcome Measure Data

Analysis Population Description

The analysis was performed on the HZ subjects from the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	391
Direct Medical Cost	189 (377)
Productivity Loss - Subject	2124 (1965)
Productivity Loss - Caregiver	82 (105)
Transport	13 (54)
Overall	297 (730)

9. Secondary Outcome

Title	Worst Pain Assessment in HZ Subjects
Description	The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. the ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.
Time Frame	At Day 90

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	391
Mean (Standard Deviation) [Scores on a scale]	0.7 (1.94)

10. Secondary Outcome

Title	Average Pain Assessment in HZ Subjects
Description	The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. the ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.
Time Frame	At Day 90

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	391
Mean (Standard Deviation) [Scores on a scale]	0.5 (1.58)

11. Secondary Outcome

Title	Impact of HZ on Quality of Life as Assessed by the Zoster Pain Inventory
Description	PHN persistence refers to pain occurring or persisting between 90-270 days after the rash onset. PHN was assessed via the Zoster Pain Inventory (ZBPI) questionnaire, which includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'.
Time Frame	At Day 0, 15, 30, 60, 90

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	391
Day 0	3.478 (2.707)
Day 15	2.742 (2.749)
Day 30	1.823 (2.459)
Day 60	1.026 (1.931)
Day 90	0.578 (1.471)

12. Secondary Outcome

Title	Impact of HZ on Quality of Life as Assessed by the EuroQoL-Five Digits
Description	EuroQoL-Five Digits (EQ-5D) is a standardised instrument for use as a measure of health outcome and is designed for self-completion by respondents. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index/scale goes from 0 (worst health state) to 1 (perfect health state).
Time Frame	At Day 0, 15, 30, 60, 90

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	391
Day 0	0.748 (0.207)
Day 15	0.801 (0.198)
Day 30	0.849 (0.207)
Day 60	0.901 (0.175)
Day 90	0.935 (0.140)

13. Secondary Outcome

Title	PHN Direct Medical Costs, Direct Non-medical Costs and Indirect Costs by Payer/Societal Perspective
Description	Cost data related to HZ included medication, procedures and referral to hospital/specialist for direct medical costs, transport for direct non-medical costs and missed time from work, sick certificate for the indirect costs.
Time Frame	Between Day 90 and Day 270

Outcome Measure Data

Analysis Population Description

The analysis was performed on the PHN subjects from the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	40
PHN, Payer	176 (179)
PHN, Societal	426 (663)

14. Secondary Outcome

Title	Worst Pain Assessment in PHN Subjects
Description	The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. the ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.
Time Frame	At Day 90

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	40
Mean (Standard Deviation) [Scores on a scale]	5.7 (1.96)

15. Secondary Outcome

Title	Average Pain Assessment in PHN Subjects
Description	The ZBPI is an assessment tool in the form of a questionnaire completed by the patient that is specifically designed to assess HZ-associated pain and discomfort. The ZBPI includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'. Note: The Day 90 window included assessments between Day 83 and Day 97 relative to day of rash onset.
Time Frame	At Day 90

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	40
Mean (Standard Deviation) [Scores on a scale]	4.2 (2.46)

16. Secondary Outcome

Title	Impact of PHN on Quality of Life as Assessed by the Zoster Pain Inventory
Description	PHN persistence refers to pain occurring or persisting between 90-270 days after the rash onset. PHN was assessed via the Zoster Pain Inventory (ZBPI) questionnaire, which includes four pain severity items (worst, least, average, present pain) and seven pain interference items which assess general activity, mood, walking ability, work, relations with others, sleep and enjoyment of life. All of the items are rated on an 11-point Likert scale (0-10). For the severity items, 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whereas for the interference items, 0 = 'does not interfere' and 10 = 'completely interferes'.
Time Frame	At Day 0, 15, 30, 60, 90

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who met all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	40
Day 0	5.967 (2.550)
Day15	6.062 (2.385)
Day 30	5.553 (2.600)
Day 60	4.315 (2.550)
Day 90	3.671 (2.145)

17. Secondary Outcome

Title	Impact of PHN on Quality of Life as Assessed by the EuroQoL-Five Digits
Description	EuroQoL-Five Digits (EQ-5D) is a standardised instrument for use as a measure of health outcome and is designed for self-completion by respondents. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was 0 (worst health state) to 1 (best health state).
Time Frame	At Day 0, 15, 30, 60, 90

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol cohort (ATP) which included all evaluable patients (i.e. those who mett all eligibility criteria and complied with the study procedures defined in the protocol).

Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
Measure Participants	40
Day 0	0.592 (0.227)
Day 15	0.582 (0.284)
Day 30	0.542 (0.317)
Day 60	0.688 (0.275)
Day 90	0.732 (0.202)

Adverse Events

Time Frame	Not applicable as serious and other adverse events were not monitored in this study
Adverse Event Reporting Description	Serious and other adverse events were not monitored in this study as this a non-interventional study based on pre-existing medical records obtained from a network of general practitioners.There was no assessment of AEs related to any treatment or vaccination in this study, as only burden of Herpes Zoster disease was assessed. Complications and clinical information of HZ cases presented in outcome measures 5-7 and deaths reported in participant flow are obtained from pre-existing medical records.
Arm/Group Title	Herpes Zoster Group
Arm/Group Description	Male or female subjects aged 50 years or above, presenting with a herpes zoster (HZ) episode.
All Cause Mortality
	Herpes Zoster Group
	Affected / at Risk (%)	# Events
Total	1/394 (0.3%)
Serious Adverse Events
	Herpes Zoster Group
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Herpes Zoster Group
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.