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DOI:
https://doi.org/10.1002/14651858.CD001364.pub4Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 18 junio 2013see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Infecciones respiratorias agudas

Copyright:
  1. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

  • Meenu Singh

    Correspondencia a: Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    [email protected]

    [email protected]

  • Rashmi R Das

    Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India

Contributions of authors

Dr Meenu Singh (MS) and Dr Rashmi Ranjan Das (RRD) jointly prepared and edited the review.

Sources of support

Internal sources

  • Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

  • All India Institute of Medical Sciences (AIIMS), New Delhi, India.

External sources

  • No sources of support supplied

Declarations of interest

None known.

Acknowledgements

We wish to thank Ian IR Marshall, the previous author of this review. We acknowledge all the help and infrastructure provided by the Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh and All India Institute of Medical Sciences (AIIMS), New Delhi. We acknowledge the help provided by Elizabeth Dooley, Managing Editor and Sarah Thorning, Trials Search Co‐ordinator of the Cochrane Acute Respiratory Infections Group, for the EMBASE search and obtaining full‐text articles of studies. We are very grateful to the following referees who commented on drafts of this review: Durhane Wong‐Rieger, Ann Fonfa, Anna Joseph, Craig Mellis, Robert Black, Conor Teljeur, Mark Jones and Paul Little.

Version history

Published

Title

Stage

Authors

Version

2015 Apr 30

Zinc for the common cold

Review

Meenu Singh, Rashmi R Das

https://doi.org/10.1002/14651858.CD001364.pub5

2013 Jun 18

Zinc for the common cold

Review

Meenu Singh, Rashmi R Das

https://doi.org/10.1002/14651858.CD001364.pub4

2011 Feb 16

Zinc for the common cold

Review

Meenu Singh, Rashmi R Das

https://doi.org/10.1002/14651858.CD001364.pub3

2006 Jul 19

Zinc for the common cold

Review

Ian IR Marshall

https://doi.org/10.1002/14651858.CD001364.pub2

1999 Apr 26

Zinc for the common cold

Review

Ian IR Marshall

https://doi.org/10.1002/14651858.CD001364

Notes

There was a change in authorship between the first published version of the review and this updated version. Ian IR Marshall was the review author of both the protocol and review published in The Cochrane Library in 1999. The review was withdrawn and taken over by the current review authors (Meenu Singh and Rashmi Ranjan Das) for updating.

Keywords

MeSH

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figuras y tablas -
Figure 1

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Forest plot of comparison: 1 Zinc versus placebo, outcome: 1.1 Duration of cold symptoms (in days).
Figuras y tablas -
Figure 3

Forest plot of comparison: 1 Zinc versus placebo, outcome: 1.1 Duration of cold symptoms (in days).

Forest plot of comparison: 1 Zinc versus placebo, outcome: 1.1 Duration of cold symptoms (in days).
Figuras y tablas -
Figure 4

Forest plot of comparison: 1 Zinc versus placebo, outcome: 1.1 Duration of cold symptoms (in days).

Forest plot of comparison: 1 Zinc versus placebo, outcome: 1.2 Severity of symptoms (score).
Figuras y tablas -
Figure 5

Forest plot of comparison: 1 Zinc versus placebo, outcome: 1.2 Severity of symptoms (score).

Forest plot of comparison: 1 Zinc versus placebo, outcome: 1.3 Incidence of common cold (IRR).
Figuras y tablas -
Figure 6

Forest plot of comparison: 1 Zinc versus placebo, outcome: 1.3 Incidence of common cold (IRR).

Comparison 1 Zinc versus placebo, Outcome 1 Duration of cold symptoms.
Figuras y tablas -
Analysis 1.1

Comparison 1 Zinc versus placebo, Outcome 1 Duration of cold symptoms.

Comparison 1 Zinc versus placebo, Outcome 2 Subgroup analysis (duration of cold symptoms).
Figuras y tablas -
Analysis 1.2

Comparison 1 Zinc versus placebo, Outcome 2 Subgroup analysis (duration of cold symptoms).

Comparison 1 Zinc versus placebo, Outcome 3 Severity of cold symptoms.
Figuras y tablas -
Analysis 1.3

Comparison 1 Zinc versus placebo, Outcome 3 Severity of cold symptoms.

Comparison 1 Zinc versus placebo, Outcome 4 Subgroup analysis (severity of cold symptoms).
Figuras y tablas -
Analysis 1.4

Comparison 1 Zinc versus placebo, Outcome 4 Subgroup analysis (severity of cold symptoms).

Comparison 1 Zinc versus placebo, Outcome 5 Incidence of common cold.
Figuras y tablas -
Analysis 1.5

Comparison 1 Zinc versus placebo, Outcome 5 Incidence of common cold.

Comparison 2 Zinc versus placebo, Outcome 1 Number of participants symptomatic after 3 days of treatment.
Figuras y tablas -
Analysis 2.1

Comparison 2 Zinc versus placebo, Outcome 1 Number of participants symptomatic after 3 days of treatment.

Comparison 2 Zinc versus placebo, Outcome 2 Number of participants symptomatic after 5 days of treatment.
Figuras y tablas -
Analysis 2.2

Comparison 2 Zinc versus placebo, Outcome 2 Number of participants symptomatic after 5 days of treatment.

Comparison 2 Zinc versus placebo, Outcome 3 Number of participants symptomatic after 7 days of treatment.
Figuras y tablas -
Analysis 2.3

Comparison 2 Zinc versus placebo, Outcome 3 Number of participants symptomatic after 7 days of treatment.

Comparison 2 Zinc versus placebo, Outcome 4 Time to resolution of cough.
Figuras y tablas -
Analysis 2.4

Comparison 2 Zinc versus placebo, Outcome 4 Time to resolution of cough.

Comparison 2 Zinc versus placebo, Outcome 5 Time to resolution of nasal congestion.
Figuras y tablas -
Analysis 2.5

Comparison 2 Zinc versus placebo, Outcome 5 Time to resolution of nasal congestion.

Comparison 2 Zinc versus placebo, Outcome 6 Time to resolution of nasal drainage.
Figuras y tablas -
Analysis 2.6

Comparison 2 Zinc versus placebo, Outcome 6 Time to resolution of nasal drainage.

Comparison 2 Zinc versus placebo, Outcome 7 Time to resolution of sore throat.
Figuras y tablas -
Analysis 2.7

Comparison 2 Zinc versus placebo, Outcome 7 Time to resolution of sore throat.

Comparison 2 Zinc versus placebo, Outcome 8 Change in cough symptom score.
Figuras y tablas -
Analysis 2.8

Comparison 2 Zinc versus placebo, Outcome 8 Change in cough symptom score.

Comparison 2 Zinc versus placebo, Outcome 9 Change in nasal symptom score.
Figuras y tablas -
Analysis 2.9

Comparison 2 Zinc versus placebo, Outcome 9 Change in nasal symptom score.

Comparison 2 Zinc versus placebo, Outcome 10 School absence (days).
Figuras y tablas -
Analysis 2.10

Comparison 2 Zinc versus placebo, Outcome 10 School absence (days).

Comparison 2 Zinc versus placebo, Outcome 11 Antibiotic use.
Figuras y tablas -
Analysis 2.11

Comparison 2 Zinc versus placebo, Outcome 11 Antibiotic use.

Comparison 2 Zinc versus placebo, Outcome 12 Any adverse event.
Figuras y tablas -
Analysis 2.12

Comparison 2 Zinc versus placebo, Outcome 12 Any adverse event.

Comparison 2 Zinc versus placebo, Outcome 13 Bad taste.
Figuras y tablas -
Analysis 2.13

Comparison 2 Zinc versus placebo, Outcome 13 Bad taste.

Comparison 2 Zinc versus placebo, Outcome 14 Nausea.
Figuras y tablas -
Analysis 2.14

Comparison 2 Zinc versus placebo, Outcome 14 Nausea.

Comparison 2 Zinc versus placebo, Outcome 15 Constipation.
Figuras y tablas -
Analysis 2.15

Comparison 2 Zinc versus placebo, Outcome 15 Constipation.

Comparison 2 Zinc versus placebo, Outcome 16 Diarrhoea.
Figuras y tablas -
Analysis 2.16

Comparison 2 Zinc versus placebo, Outcome 16 Diarrhoea.

Comparison 2 Zinc versus placebo, Outcome 17 Abdominal pain.
Figuras y tablas -
Analysis 2.17

Comparison 2 Zinc versus placebo, Outcome 17 Abdominal pain.

Comparison 2 Zinc versus placebo, Outcome 18 Dry mouth.
Figuras y tablas -
Analysis 2.18

Comparison 2 Zinc versus placebo, Outcome 18 Dry mouth.

Comparison 2 Zinc versus placebo, Outcome 19 Mouth irritation.
Figuras y tablas -
Analysis 2.19

Comparison 2 Zinc versus placebo, Outcome 19 Mouth irritation.

Zinc compared with placebo for the common cold

Patient or population: patients with common cold

Settings: outpatient

Intervention: zinc lozenges or syrup

Comparison: usual care

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Zinc

Duration of cold symptoms (days)

The mean duration of cold symptoms ranged across control groups from 5.1 to 9.38 days

The mean duration of cold symptoms ranged across control groups from 4 to 12.1 days

1656
(14 studies1)

++O
low2,3‐5

Severity of symptom score

The mean severity of symptom score ranged across control groups from 0.4 to 5.61

The mean severity of symptom score ranged across control groups from 0.2 to 3.45

513
(5 studies6)

++O
low3,5,7,8

Incidence of common cold

618 per 1000

382 per 1000 (354 to 431)

RR 0.64 (0.47 to 0.88)

394
(2 studies9)

+OO
very low3,10‐12

Number of participants symptomatic after 7 days of treatment

563 per 1000

373 per 1000 (143 to 508)

OR 0.45 (0.2 to 1.0)

476
(5 studies13)

++OO
very low14‐16

School absence (number of days)

The mean days of school absence ranged across control groups from 1.3 to 1.35 days

The mean days of school absence in the intervention groups was 0.37 lower (0.7 to 0.04 lower)

394
(2 studies9)

+OO
very low10,17,18

Antibiotic use

330 per 1000

127 per 1000 (52 to 200)

OR 0.27 (0.16 to 0.46)

394
(2 studies9)

++OO
low10,19,20

Any adverse event

349 per 1000

424 per 1000 (132 to 898)

OR 1.58 (1.19 to 2.09)

1217
(8 studies)

+++O
moderae21‐23

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval
RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1No serious study limitations: all the studies had adequately concealed allocation and blinded both participants and study staff to be considered at low risk of bias. Whether free of other bias was unclear in Macknin 1998; Petrus 1998; Turner 2000a; Turner 2000b; Turner 2000c. Petrus 1998 did not adequately describe the sequence generation. Blinding was inadequate in Turner 2000a; Turner 2000b; Turner 2000c.

2Serious inconsistency: there was high statistical heterogeneity. I2 statistic = 89%. The heterogeneity was due to differences in the nature of the different interventions (zinc gluconate versus acetate lozenges, zinc lozenges versus zinc syrup), wide dose ranges, varied duration of symptoms prior to administration of zinc (varying from 24 to 48 hours) and characteristics of the study population (children versus adults).

3No serious indirectness: studies both from low‐income and high‐income regions have assessed this comparison. Therefore, the result can be confidently generalised to all situations.

4No serious imprecision: though the 95% CI around the pooled effect is narrow, the lower limit does not suggest a clinically important reduction in the duration of cold (a decrease in duration of ≤ 1 day is not shown to be important to patients).

5Publication bias cannot be ruled out.

6No serious study limitation: all the studies had adequately concealed allocation and blinded both participants and study staff to be considered at low risk of bias. Whether free of other bias was unclear and adequate sequence was not generated in one study (Petrus 1998).

7Serious imprecision: the 95% CI around the pooled effect is wide, the lower limit is crossing the point of no effect.

8Serious inconsistency: there was high statistical heterogeneity. I2 statistic = 84%. The heterogeneity may be due to differences in the nature of the different interventions (zinc gluconate or acetate lozenges, zinc sulphate syrup) and dose range (30 to 160 mg/day) as well as mean duration of symptoms prior to administration of zinc (varying from 24 to 48 hours), as well as the characteristics of the study population (children versus adults). However, subgroup analysis was not possible as there were not enough studies for each variable.

9Kurugol 2006b is a community‐based intervention including 200 healthy school children and studying the effect of daily administration of 15 mg zinc sulphate syrup over a period of seven months. Vakili 2009 is also a community‐based intervention including 200 healthy school children and studying the effect of daily administration of 10 mg zinc sulfate tablets over a period of seven months.

10Serious study limitation: though the study by Kurugol 2006b was of high quality, that by Vakili 2009 was of poor methodological quality.

11Serious inconsistency: there is substantial heterogeneity between the two trials: I2 statistic for heterogeneity = 88%. Both trials showed a benefit with zinc, however the size of this effect was much larger in Vakili 2009. The heterogeneity was due to differences in the trial methodology and the nature of the interventions.

12No serious imprecision: the 95% CI around the pooled effect is narrow. Even the lower limit suggests a clinically important reduction in the incidence rate ratio of cold which is shown to be important to patients.

13No serious study limitations: allocation concealment was unclear in two studies, i.e. Smith 1989 and Weismann 1990, though both the studies blinded both participants and study staff.

14Serious inconsistency: there was high statistical heterogeneity. I2 statistic = 75%. The heterogeneity may be due to differences in the nature of the different interventions (zinc gluconate or acetate lozenges) and dose range (30 to 160 mg/day) as well as mean duration of symptoms prior to administration of zinc (varying from 24 to 48 hours, as well as the characteristics of the study population (children versus adults). However, subgroup analysis was not possible as there were not enough studies for each variable.

15Serious indirectness: only studies from high‐income regions have assessed this comparison. Therefore, the result cannot be generalised to all situations.

16No serious imprecision: both limits of the 95% CI suggest a clinically important reduction in proportion of participants given the intervention symptomatic after seven days of treatment.

17Serious inconsistency: there is substantial heterogeneity between the two trials: I2 statistic test for heterogeneity = 64%. Both trials showed reduced days of school absence with intervention, however, the size of this effect was much larger in Kurugol 2006b. The heterogeneity was due to differences in the trial methodology and the nature of the interventions.

18No serious imprecision: though the 95% CI around the pooled effect is narrow, the lower limit does not suggests a clinically important reduction in the duration of school absence (a decrease in duration of ≤ 1 day is not shown to be important to patients).

19No serious inconsistency: there was no statistical heterogeneity. I2 statistic = 0%.

20No serious imprecision: both limits of the 95% CI suggest a clinically important reduction in the rate of antibiotic use with intervention.

21No serious study limitations: all the studies had adequately concealed allocation (except Weismann 1990, in which allocation concealment is unclear) and blinded both participants and study staff to be considered at low risk of bias. Whether free of other bias was unclear in Macknin 1998 and Weismann 1990. Weismann 1990 did not adequately describe the sequence generation.

22No serious inconsistency: there is no statistical heterogeneity. I2 statistic = 21%. Both the lozenges and syrup preparation trials were pooled.

23No serious imprecision: the 95% CI around the pooled effect is narrow. The resulting adverse events from use of zinc are higher and this is significant.

Figuras y tablas -
Comparison 1. Zinc versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Duration of cold symptoms Show forest plot

14

1656

Mean Difference (IV, Random, 95% CI)

‐1.03 [‐1.72, ‐0.34]

2 Subgroup analysis (duration of cold symptoms) Show forest plot

14

5996

Mean Difference (IV, Random, 95% CI)

‐1.07 [‐1.43, ‐0.71]

2.1 Dose of zinc ≥ 75 mg/day

7

620

Mean Difference (IV, Random, 95% CI)

‐1.97 [‐3.09, ‐0.85]

2.2 Dose of zinc < 75 mg/day

5

722

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.54, 0.79]

2.3 Zinc gluconate lozenges

6

798

Mean Difference (IV, Random, 95% CI)

‐0.81 [‐1.86, 0.25]

2.4 Zinc acetate lozenges

6

544

Mean Difference (IV, Random, 95% CI)

‐1.21 [‐2.69, 0.28]

2.5 Zinc lozenges

12

1342

Mean Difference (IV, Random, 95% CI)

‐1.04 [‐2.02, ‐0.05]

2.6 Zinc syrup

2

314

Mean Difference (IV, Random, 95% CI)

‐0.65 [‐0.92, ‐0.39]

2.7 Children < 16 years age

3

561

Mean Difference (IV, Random, 95% CI)

‐0.62 [‐0.82, ‐0.42]

2.8 Adults

11

1095

Mean Difference (IV, Random, 95% CI)

‐1.12 [‐2.17, ‐0.06]

3 Severity of cold symptoms Show forest plot

5

513

Mean Difference (IV, Random, 95% CI)

‐1.06 [‐2.36, 0.23]

4 Subgroup analysis (severity of cold symptoms) Show forest plot

5

513

Mean Difference (IV, Random, 95% CI)

‐1.06 [‐2.36, 0.23]

4.1 Zinc lozenges

3

199

Mean Difference (IV, Random, 95% CI)

‐1.55 [‐3.62, 0.52]

4.2 Zinc syrup

2

314

Mean Difference (IV, Random, 95% CI)

‐0.27 [‐1.51, 0.97]

5 Incidence of common cold Show forest plot

2

1522

Risk Ratio (M‐H, Random, 95% CI)

0.64 [0.47, 0.88]

Figuras y tablas -
Comparison 1. Zinc versus placebo
Comparison 2. Zinc versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants symptomatic after 3 days of treatment Show forest plot

3

340

Odds Ratio (M‐H, Random, 95% CI)

0.81 [0.27, 2.42]

2 Number of participants symptomatic after 5 days of treatment Show forest plot

3

340

Odds Ratio (M‐H, Random, 95% CI)

0.78 [0.32, 1.95]

3 Number of participants symptomatic after 7 days of treatment Show forest plot

5

476

Odds Ratio (M‐H, Random, 95% CI)

0.45 [0.20, 1.00]

4 Time to resolution of cough Show forest plot

4

453

Mean Difference (IV, Random, 95% CI)

‐1.73 [‐3.49, 0.03]

5 Time to resolution of nasal congestion Show forest plot

5

605

Mean Difference (IV, Random, 95% CI)

‐0.70 [‐1.39, ‐0.01]

6 Time to resolution of nasal drainage Show forest plot

5

599

Mean Difference (IV, Random, 95% CI)

‐1.01 [‐2.01, ‐0.01]

7 Time to resolution of sore throat Show forest plot

4

430

Mean Difference (IV, Fixed, 95% CI)

‐0.46 [‐0.82, ‐0.09]

8 Change in cough symptom score Show forest plot

1

101

Mean Difference (IV, Fixed, 95% CI)

‐0.23 [‐0.26, ‐0.20]

9 Change in nasal symptom score Show forest plot

2

314

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐1.34, 0.94]

10 School absence (days) Show forest plot

2

394

Mean Difference (IV, Fixed, 95% CI)

‐0.66 [‐0.99, ‐0.33]

11 Antibiotic use Show forest plot

2

394

Odds Ratio (M‐H, Fixed, 95% CI)

0.27 [0.16, 0.46]

12 Any adverse event Show forest plot

8

1217

Odds Ratio (M‐H, Fixed, 95% CI)

1.58 [1.19, 2.09]

12.1 Lozenge formulation

6

897

Odds Ratio (M‐H, Fixed, 95% CI)

2.00 [1.40, 2.86]

12.2 Syrup formulation

2

320

Odds Ratio (M‐H, Fixed, 95% CI)

1.03 [0.64, 1.66]

13 Bad taste Show forest plot

12

1483

Odds Ratio (M‐H, Fixed, 95% CI)

2.31 [1.71, 3.11]

13.1 Lozenges formulation

10

1163

Odds Ratio (M‐H, Fixed, 95% CI)

2.66 [1.91, 3.69]

13.2 Syrup formulation

2

320

Odds Ratio (M‐H, Fixed, 95% CI)

1.15 [0.55, 2.39]

14 Nausea Show forest plot

8

932

Odds Ratio (M‐H, Fixed, 95% CI)

2.15 [1.44, 3.23]

14.1 Lozenges formulation

6

612

Odds Ratio (M‐H, Fixed, 95% CI)

2.46 [1.56, 3.89]

14.2 Syrup formulation

2

320

Odds Ratio (M‐H, Fixed, 95% CI)

1.24 [0.50, 3.08]

15 Constipation Show forest plot

7

874

Odds Ratio (M‐H, Fixed, 95% CI)

1.60 [0.82, 3.10]

15.1 Lozenges formulation

5

554

Odds Ratio (M‐H, Fixed, 95% CI)

2.00 [0.88, 4.55]

15.2 Syrup formulation

2

320

Odds Ratio (M‐H, Fixed, 95% CI)

1.0 [0.31, 3.21]

16 Diarrhoea Show forest plot

6

764

Odds Ratio (M‐H, Fixed, 95% CI)

1.89 [0.92, 3.89]

16.1 Lozenges formulation

4

444

Odds Ratio (M‐H, Fixed, 95% CI)

2.09 [0.92, 4.75]

16.2 Syrup formulation

2

320

Odds Ratio (M‐H, Fixed, 95% CI)

1.34 [0.30, 6.09]

17 Abdominal pain Show forest plot

6

824

Odds Ratio (M‐H, Fixed, 95% CI)

1.31 [0.83, 2.07]

17.1 Lozenges formulation

4

504

Odds Ratio (M‐H, Fixed, 95% CI)

1.27 [0.76, 2.11]

17.2 Syrup formulation

2

320

Odds Ratio (M‐H, Fixed, 95% CI)

1.52 [0.53, 4.33]

18 Dry mouth Show forest plot

7

874

Odds Ratio (M‐H, Fixed, 95% CI)

1.37 [0.95, 1.99]

18.1 Lozenges formulation

5

554

Odds Ratio (M‐H, Fixed, 95% CI)

1.42 [0.95, 2.11]

18.2 Syrup formulation

2

320

Odds Ratio (M‐H, Fixed, 95% CI)

1.13 [0.43, 3.01]

19 Mouth irritation Show forest plot

7

822

Odds Ratio (M‐H, Fixed, 95% CI)

1.15 [0.77, 1.73]

19.1 Lozenges formulation

5

502

Odds Ratio (M‐H, Fixed, 95% CI)

1.08 [0.67, 1.73]

19.2 Syrup formulation

2

320

Odds Ratio (M‐H, Fixed, 95% CI)

1.40 [0.62, 3.15]

Figuras y tablas -
Comparison 2. Zinc versus placebo