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3.1 Evaluación de la migración leucocitaria en embriones de Danio rerio (pez zebra).

Table 8outlines the outcome measures and delivery time points.

Demography and baseline assessment

Appendix 3includes an example of the CRF listing the demographic and clinical data that were collected at pre-enrolment and pre-randomisation stages. This includes the baseline assessments that are carried out during visit‘A’at the time of enrolment.

Clinical outcomes

For the randomised pilot trial we used a package of outcome measures consistent with consensus recommendations for outcome assessment in back pain trials. These included pain measurement, physical function, emotional function, back-related function, generic well-being, disability (social role), satisfaction with care, patient rating of improvement and satisfaction with treatment, symptoms (pain), adverse events, participant disposition and a modified form of the Patient Generated Index (PGI).67,108In this feasibility

trial we assessed performance of these measures and with a view to reducing the questionnaire burden in the main trial.

Table 8summarises the outcome measures and their time of completion by participants. The main

questionnaire packages are completed at baseline (at trial entry assessment) and follow-up (3 and 6 months post randomisation). A pain severity (today) score was recorded daily for 35 days from 7 days before first treatment session and following this weekly until 3-month follow-up. Health utility (EQ-5D-5L) was recorded weekly from 1 week prior to first treatment session until the night before injection appointment when we asked participants to record it daily for 8 days and then weekly until the 3-month follow-up. In addition, intervention participants record a pain severity 45–60 minutes before and after receiving an injection. Clinical data were collected and recorded by physiotherapists and clinicians, covering patients’assessments, injections and involvement in the physiotherapy intervention. Copies of questionnaires are provided inAppendices 4and5.

Primary outcome

The primary outcome for this feasibility trial was a numerical rating scale for pain collected via text messaging over 3 months following randomisation.84

A method for frequent (daily) collection of pain-related outcome data using a text messaging system was developed and piloted within the feasibility trial. To test the feasibility of using an electronic diary, a review of studies using electronic diary-related pain or pain-related disability measurement was conducted, as well as the identification or development of an application or text system with candidate diary prompts and

choice of prompts and frequency.117Research participants find electronic symptom diaries acceptable and

can generate valid symptom data.118During the exploratory phase, initial feasibility testing, we refined the

diary recording for the needs of the trial.

For those participants unable or unwilling to use a text messaging system, we used a paper-based system. We collected data on pain severity using an 11-point numerical rating scale (Pain-NRS).84Data on pain were

collected daily for 35 days starting 1 week prior to randomisation and then weekly for until 3 months after randomisation. It was felt that any benefit or harm in the immediate post-injection period was likely to change on a daily basis, and, therefore, less frequent data collection should identify any between-group differences.

Our second primary outcome focused on back pain related disability. We used the RMDQ at baseline and

TABLE 8 Outcome measures and delivery time points

Type of data Outcome measures

Time points

1a 2b 3c 4d 5e

Demographic Age, gender, ethnic group, age at leaving full-time

education, occupation, current work status

Yes

History Time since completely free of back pain Yes

History Previous back pain treatments Yes

Medications Current medications Yes Yes

History Satisfaction with health state Yes Yes

History Troublesomeness question Yes Yes

Back pain related disability RMDQ83

Yes Yes

Back pain related disability The MVK questionnaire disability score84,99 Yes Yes

Back Pain Severity The MVK questionnaire pain scale99

Yes Yes

Modified form of PGI109,110 Yes Yes

Psychological distress DAPOS111

Yes Yes

Pain self-efficacy Pain self-efficacy questionnaire112 Yes Yes

Health-related quality of life SF-12v2, reported as physical and mental

component scores113

Yes Yes

Health utilities EQ-5D-5L114,115 Yes Yes Yes Yes

Well-being WEMWEBS116

Yes Yes

Pain distribution Troublesomeness grid103 Yes

Back Pain Severity today 11-point pain rating scale84

Yes Yes

Current work status If appropriate date of return to work Yes

Health and social service resource use

Including hospital and community resource, as well as costs to individuals and carers

Yes DAPOS, Depression, Anxiety, and Positive Outlook Scale; MVK, Modified Von Korff; SF-12v2, Short Form questionnaire-12 items version 2; WEMWEBS, Warwick–Edinburgh Mental Well-Being Scale.

a Baseline: following clinical assessment.

b Intervention only: day of injection 45–60 minutes before and after injection.

c Daily pain score: for a period of 35 days starting 7 days before first physiotherapy treatment (via text messaging), after which weekly until the end point (3 months).

d EQ-5D-5L: weekly from first physiotherapy treatment session until the night before injection appointment when daily for 8 days; then back to weekly until the end point (3 months).

It was planned that the between-group analysis would be looking for a‘signal’that the intervention package might be effective. If we failed to find an indication that there may be a worthwhile benefit, there would be no need to proceed to a full trial. We were not, here, interested in the point estimate for any between-group differences. Rather, we were interested in whether or not it was plausible that FJIs would achieve a benefit of sufficient magnitude to make them a worthwhile intervention. Thus, a decision not to proceed to a main trial would have been based on it being implausible that the intervention would achieve a worthwhile clinical effect. The size of effect below which the clinical and academic community accept that the use of FJIs was not worth considering was decided at the consensus development conference. However, because of the early closure of recruitment, no between-group analyses were undertaken (seeAnalyses).

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