PROSPERO International prospective register of systematic reviews

Review title and timescale

1

Review title

Give the working title of the review. This must be in English. Ideally it should state succinctly the interventions or exposures being reviewed and the associated health or social problem being addressed in the review.

Andrographis paniculata for symptomatic relief of acute respiratory tract infections in adults and children: a systematic review and meta-analysis

2

Original language title

For reviews in languages other than English, this field should be used to enter the title in the language of the review. This will be displayed together with the English language title.

3

Anticipated or actual start date

Give the date when the systematic review commenced, or is expected to commence.

22/02/2016

4

Anticipated completion date

Give the date by which the review is expected to be completed.

30/09/2016

5

Stage of review at time of this submission

Indicate the stage of progress of the review by ticking the relevant boxes. Reviews that have progressed beyond the point of completing data extraction at the time of initial registration are not eligible for inclusion in PROSPERO. This field should be updated when any amendments are made to a published record.

 
The review has not yet started ×    
     
Review stage Started Completed
Preliminary searches Yes Yes
Piloting of the study selection process Yes Yes
Formal screening of search results against eligibility criteria Yes No
Data extraction No No
Risk of bias (quality) assessment No No
Data analysis No No
 

Provide any other relevant information about the stage of the review here.

Review team details

6

Named contact

The named contact acts as the guarantor for the accuracy of the information presented in the register record.

Xiao-Yang Hu

7

Named contact email

Enter the electronic mail address of the named contact.

X.Hu@soton.ac.uk

8

Named contact address

Enter the full postal address for the named contact.

Complementary and Integrated Medicine Research Unit, Primary Care and Population Sciences, Faculty of Medicine, University of Southampton Aldermoor Health Centre, Aldermoor Close, Southampton SO16 5ST

9

Named contact phone number

Enter the telephone number for the named contact, including international dialing code.

+44 (0)23 8024 4085

10

Organisational affiliation of the review

Full title of the organisational affiliations for this review, and website address if available. This field may be completed as 'None' if the review is not affiliated to any organisation.

Complementary and Integrated Medicine, Primary Medical Care, University of Southampton

Website address:

www.southampton.ac.uk/camresearchgroup

11

Review team members and their organisational affiliations

Give the title, first name and last name of all members of the team working directly on the review. Give the organisational affiliations of each member of the review team.

 
Title First name Last name Affiliation
Xiao-YangHuUniversity of Southampton
MargaretBellPatient representative
Yu-TongFeiBeijing University of Chinese Medicine
AndrewFlowerUniversity of Southampton
Lily YuenLaiUniversity of Southampton
Jian-PingLiuBeijing University of Chinese Medicine
MartinLogueUniversity of Southampton
JoanneLordUniversity of Southampton
MichaelMooreUniversity of Southampton
BethStuartUniversity of Southampton
Ruo-HanWuBeijing University of Chinese Medicine
GeorgeLewithUniversity of Southampton

12

Funding sources/sponsors

Give details of the individuals, organizations, groups or other legal entities who take responsibility for initiating, managing, sponsoring and/or financing the review. Any unique identification numbers assigned to the review by the individuals or bodies listed should be included.

This systematic review is funded by the National Institute for Health Research School for Primary Care Research (Project No: 276, Funding round: FR 9).

13

Conflicts of interest

List any conditions that could lead to actual or perceived undue influence on judgements concerning the main topic investigated in the review.

Are there any actual or potential conflicts of interest?

None known

14

Collaborators

Give the name, affiliation and role of any individuals or organisations who are working on the review but who are not listed as review team members.

 
Title First name Last name Organisation details
JeremyHowickCentre of Evidence-Based Medicine, University of Oxford
Review methods

15

Review question(s)

State the question(s) to be addressed / review objectives. Please complete a separate box for each question.

This systematic review will evaluate clinical efficacy, effectiveness and adverse events of Andrographis paniculata for symptoms of acute respiratory tract infections (ARTIs).

16

Searches

Give details of the sources to be searched, and any restrictions (e.g. language or publication period). The full search strategy is not required, but may be supplied as a link or attachment.

MEDLINE, EMBASE, AMED, Cochrane Library, CINAHL, China National Knowledge Infrastructure (CNKI), Wan Fang, Sino-Med Database, and Chinese Science and Technology Journal Database (VIP) will be searched from their inception to March 2016. A range of text words and indexed terms related to “andrographis paniculata” and “respiratory tract infection” will be searched. The reference lists of studies meeting the inclusion criteria will be searched to identify additional relevant studies. A detailed search strategy and search term alternatives for each database are available in the appendix. There will be no exclusions made based on language. Two researchers will screen references for eligibility independently. Study authors will be contacted to obtain relevant missing data if necessary and where resources allow.

17

URL to search strategy

If you have one, give the link to your search strategy here. Alternatively you can e-mail this to PROSPERO and we will store and link to it.

http://www.crd.york.ac.uk/PROSPEROFILES/35679_STRATEGY_20160313.pdf


I give permission for this file to be made publicly available

Yes

18

Condition or domain being studied

Give a short description of the disease, condition or healthcare domain being studied. This could include health and wellbeing outcomes.

ATRIs in adults and children

19

Participants/population

Give summary criteria for the participants or populations being studied by the review. The preferred format includes details of both inclusion and exclusion criteria.

Studies of human participants of all ages, with symptoms of ARTIs. A clinical diagnosis of ARTI will be main inclusion criteria. Diagnoses of upper or lower ARTIs include acute common cold, influenza, rhinosinusitis, laryngitis, tonsillitis, pharyngitis, croup, acute otitis media, bronchitis, pneumonia, and acute exacerbations of chronic obstructive pulmonary disease (COPD). Symptoms of ARTIs are defined as having symptoms such as cough, sore throat, fever, runny nose, discoloured sputum etc, for a duration of less than four weeks. Trials will be excluded if they evaluated patients with asthma, had active or previous peptic ulceration, were hypersensitive to analgesics, had psychosis, or were severely depressed. Exclusion also applied to trials of patients who required hospital admission (for example, for meningitis, severe pneumonia, epiglottitis, or Kawasaki disease), had a known immune deficiency, or were pregnant or breastfeeding (Little et al., 2014).

20

Intervention(s), exposure(s)

Give full and clear descriptions of the nature of the interventions or the exposures to be reviewed

Any form of oral A. paniculata either monograph, or in an herbal mixture (A. paniculata in multi-ingredient formulation) for symptoms of ARTIs. Examples of herbal mixture include: products contain A. paniculata in combination with Scutellaria baicalensis, or in combination with Lonicera japonica, Forsythia suspense, and Aster trinervius. No limitation will be imposed concerning dosage, methods of dosing or duration of administration.

21

Comparator(s)/control

Where relevant, give details of the alternatives against which the main subject/topic of the review will be compared (e.g. another intervention or a non-exposed control group).

Placebo or no intervention; usual care such as analgesics, antivirals, antibiotics, anti-inflammatories, steroids or corticosteroids; or other herbal remedies. Studies comparing different preparations of Andrographis, e.g. comparing tablet with granule preparations, will also be included in this review. Potential groups will be included in this review are: A. paniculata versus placebo A. paniculata versus no intervention A. paniculata versus usual care/standard care/biomedical conventional treatment A. paniculata versus a different herbal intervention A. paniculata (e.g. tablet) versus A. paniculata (e.g. liquid)

22

Types of study to be included

Give details of the study designs to be included in the review. If there are no restrictions on the types of study design eligible for inclusion, this should be stated.

This review will include published and unpublished randomised controlled trials (RCTs). Quasi-RCTs, crossover trials, controlled before and after studies, interrupted time series (ITS) studies, and non-experimental studies will not be included due to their potential high risk of bias.

23

Context

Give summary details of the setting and other relevant characteristics which help define the inclusion or exclusion criteria.

24

Primary outcome(s)

Give the most important outcomes.

Primary outcome measures will be: 1) The mean improvement in RTI symptoms. This may be measured by participant self-report or by clinician/observer assessment. Commonly used measures include: • Changes on visual analogue scales in key symptoms, including temperature, cough, catarrh, etc. • Changes in symptoms scored on a Likert-type scale • Global assessment of symptom improvement by the patient • Global assessment of symptom improvement by treating clinician When individual symptoms are reported, data on two key symptoms: cough and sore throat will be collected as the target symptoms for this review. If these are not available data on overall symptom scores (sum of various symptoms such as temperature, cough, catarrh etc) will be collected and analysed. 2) Adverse events (AEs) includes any anaphylactic, allergic reactions, hypersensitivity reactions, or complications of A. paniculata, such as rash, nausea, fatigue, or worsening of symptoms. AEs due to interactions between A. paniculata in combination with other remedies, or potential interactions with other medications patients take for their co-morbidities will also be collected. Any serious AEs defined according to the International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines as any event that leads to death, is life-threatening, requires hospitalisation or leads to persistent or significant disability; biochemistry results such as electrolytes, liver and kidney function tests (alanine aminotransferase and creatinine) (ICH, 1999).

Give information on timing and effect measures, as appropriate.

25

Secondary outcomes

List any additional outcomes that will be addressed. If there are no secondary outcomes enter None.

1). Mean time to reported remission or resolution of symptoms. This may be measured directly, through patient or clinician/observer report or indirectly as the time to return to normal activities. 2). Reduction in reported antibiotic usage, e.g. number of scripts issued immediate at the time of consultation and update of delayed prescriptions Trials that do not report either our primary and or secondary outcome measures will be excluded from this review.

 

Give information on timing and effect measures, as appropriate.

Timing of effect measures: Some studies may have used a repeated measures approach. Timings of measures for each included trial will be documented with commonly reported time points explored if there was sufficient data available. All outcome measures will be assessed at baseline and the most appropriate follow-up if data available. Otherwise, data at the most appropriate follow-up point will be assessed.

26

Data extraction (selection and coding)

Give the procedure for selecting studies for the review and extracting data, including the number of researchers involved and how discrepancies will be resolved. List the data to be extracted.

A data extraction spreadsheet will be designed and piloted and appropriate changes made for this review. The form will identify trial characteristics, clinical characteristics of A. paniculata considered the items suggested in the consolidated standards of reporting trials (CONSORT) herbal extension in terms of features of herbal intervention (Gagnier et al., 2006), quality assessment, and findings on efficacy, effectiveness and AEs. Two reviewers will extract study data independently, with findings compared and agreed. The following data will be extracted from included studies if available: Details of the study: Aim of study; Study design. Population: Methods of recruitment; Diagnosis and inclusion/exclusion criteria for patients; Syndrome differentiation (if available); Course of conditions/symptoms; Other health problems; Number of patients: screened, eligible, enrolled, randomised to intervention, randomised to control, excluded post randomisation, withdrawn, lost to follow up, included in analysis and each outcome measures; Age; Gender; Geographic location (eg. City/State/Country); Ethnicity; and informed consent. Details of treatment: Name of the product that contains A. paniculata or its constituents (if relevant); Manufacturer (company or pharmacy); Use of internationally agreed nomenclature to identify herbal components; Retention of a voucher specimen of any processed plants; A. paniculata monograph or herbal mixture (in multi-ingredient formulation); A. paniculata formulation that includes details on: Dose form(s), e.g. film coated/sugar coated tablets, hard/soft/enteric coated capsules, liquids, granules, etc; Type of product used, e.g. raw (fresh or dry), extract; Methods of measuring the proportion of andrographolide (if available); The content (e.g. as weight, concentration may be given as range where appropriate) of active ingredients in A. paniculata product; Added materials, such as binders, fillers, and other excipients; and Dose strength(s); Regimen; Herbal mixture details (Botanical Latin, family, pharmaceutical Latin, Chinese pinyin); and co-intervention details. Details of comparison: Types of control, e.g. placebo, usual care; Details of control intervention and regimen. Details of providers, e.g. was practitioner involved etc. Details of AEs: Any AE reported (whether reference or definition of AE was provided); Any acute toxicity reported; Probability of herb toxicity effect, e.g. low, medium, high; Mentioning of contraindications or cautions, tolerability; Potential causative ingredient; Whether the product used is appropriately authorised by country (licensed, registered); and Qualitative testing: product’s chemical fingerprint and methods used, any special testing/purity testing performed, and details of standardisation. Proportion of patients who experienced AEs in the intervention group and controlled group will also be collected, with P value provided if available.

27

Risk of bias (quality) assessment

State whether and how risk of bias will be assessed, how the quality of individual studies will be assessed, and whether and how this will influence the planned synthesis.

The risk of bias of the included RCTs will be assessed independently by two reviewers using the tool developed by Higgins and Green in the Cochrane Handbook for Systematic Reviews of Interventions (Collaboration et al., 2011). We will assess bias over the following domains: Selection bias (random sequence generation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (blinding of researchers conducting outcome assessments), attrition bias (incomplete outcome data), reporting bias (selective reporting), and other sources of bias. A judgement of ‘low risk’ of bias, ‘high risk’ or bias, or ‘unclear risk’ of bias will be provided for each domain. Any disagreements will be resolved by discussion or by involving a third reviewer until consensus is reached.

28

Strategy for data synthesis

Give the planned general approach to be used, for example whether the data to be used will be aggregate or at the level of individual participants, and whether a quantitative or narrative (descriptive) synthesis is planned. Where appropriate a brief outline of analytic approach should be given.

We will combine data from individual studies in a meta-analysis only where appropriate. Overall effect sizes will be estimated using Review Manager (RevMan) Version [5.3]. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. A generic inverse variance random effects model will be used to pool the mean difference (MD) with 95% confidence interval (CI) on target continuous outcomes. It is anticipated that the units of the outcome measures used across studies may not be consistent and therefore it is likely that we will report the effects as standardised mean differences (SMD) rather than MD. A random effects model will be used as it incorporates heterogeneity both within and between studies (Higgin and Green, 2011), e.g. heterogeneity between studies’ follow-up length will be accounted for by use of a random effects model. For dichotomous data, a random effects method will be used to pool the summary risk ratio (RR) with 95% CI. An overall effect size with 0.2-0.5 will be regarded as small, 0.5-0.8 as moderate and more than 0.8 as large (Cohen, 1988). Absolute risk estimates will be calculated using the event rates of controlled groups as baseline risks. Dealing with missing data Where data is missing or incomplete, we will contact study authors to obtain this where possible. If means but not standard deviations have been reported, we will attempt to calculate the standard deviation from the information reported such as p-values, F-values or confidence intervals. As far as possible, we will perform an intention to treat (ITT) analysis for all outcomes. However, it is likely that many studies will report complete cases only. Assessment of heterogeneity We will assess between study heterogeneity using the I-squared statistic which describes the percentage of variation across studies that is due to heterogeneity rather than chance. Rules of thumb for interpretation of this statistic suggest that I-squared >30% equates to moderate heterogeneity, I-squared >50% equates to substantial heterogeneity and I-squared >75% equates to considerable heterogeneity (Higgin and Green, 2011). For all I-squared values about 50%, we will investigate sources of heterogeneity. Although this threshold is widely used, it is somewhat arbitrary and therefore if the I-squared value is below 50% but the direction and magnitude of treatment effects suggest important heterogeneity, we will investigate the potential sources in a sensitivity analysis and take this into account when interpreting the findings. Assessment of reporting biases Funnel plots will be created to investigate potential reporting bias where this is feasible and there are sufficient studies (Egger et al., 1997). Funnel plot tests for asymmetry will be separately conducted in STATA, using the metabias command.

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Analysis of subgroups or subsets

Give any planned exploration of subgroups or subsets within the review. ‘None planned’ is a valid response if no subgroup analyses are planned.

Sensitivity analysis If sufficient number of trials were identified with the same interventions, sensitivity analysis will be conducted for the primary outcomes to determine whether the review conclusions would have differed if eligibility was restricted to trials without high risk of bias; and if eligibility was restricted to trails that provided any detail on authentication/standardisation of the herb. Subgroup analysis If there is sufficient available data, several subgroup analyses will be conducted to compare the effect estimate between studies that evaluate: • Patients with upper RTI versus lower RTI; • Adults versus children (younger than 18); • Andrographis paniculata as monotherapy versus as fixed combinations; • Andrographis paniculata in different preparation, e.g. granule versus tablet or other forms

Review general information

30

Type and method of review

Select the type of review and the review method from the drop down list.

Intervention

31

Language

Select the language(s) in which the review is being written and will be made available, from the drop down list. Use the control key to select more than one language.

English

Will a summary/abstract be made available in English?

Yes

32

Country

Select the country in which the review is being carried out from the drop down list. For multi-national collaborations select all the countries involved. Use the control key to select more than one country.

England, China

33

Other registration details

Give the name of any organisation where the systematic review title or protocol is registered together with any unique identification number assigned. If extracted data will be stored and made available through a repository such as the Systematic Review Data Repository (SRDR), details and a link should be included here.

34

Reference and/or URL for published protocol

Give the citation for the published protocol, if there is one.

Give the link to the published protocol, if there is one. This may be to an external site or to a protocol deposited with CRD in pdf format.


I give permission for this file to be made publicly available

Yes

35

Dissemination plans

Give brief details of plans for communicating essential messages from the review to the appropriate audiences.

Do you intend to publish the review on completion?

Yes

36

Keywords

Give words or phrases that best describe the review. (One word per box, create a new box for each term)

andrographis

andrographis paniculata

acute respiratory tract infection

systematic review

meta-analysis

37

Details of any existing review of the same topic by the same authors

Give details of earlier versions of the systematic review if an update of an existing review is being registered, including full bibliographic reference if possible.

38

Current review status

Review status should be updated when the review is completed and when it is published.

Ongoing

39

Any additional information

Provide any further information the review team consider relevant to the registration of the review.

40

Details of final report/publication(s)

This field should be left empty until details of the completed review are available.
Give the full citation for the final report or publication of the systematic review.

Give the URL where available.

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