The study will be a prospective, four-arm randomized control trial (RCT) with the assessor and participant blinded to group allocation. 160 patients with cervical radiculopathy for more than 6 months will be enrolled with a hospital-based randomization process in 4 specialized centers of Dhaka to be recruited between July and December 2022. With a concealed allocation process, the patient will be recruited to any of the specialized physiotherapy approach groups, enrollment in only pain medication groups will be convenient to the respondents who willingly want to take medications only or dropped out from physiotherapy sessions after the initial day of assessment and management. All groups will have a similar number of respondents (n=40). For this trial, we will follow Standard Protocol Items: Interventional Trials 2013 (SPIRIT) guidelines, to maintain the quality of the interventional trial ( Table 1).

Participants will be recruited and treated in three specialized physiotherapy set-ups, and one specialized hospital. The specialized physiotherapy setup includes the Agrani Specialized Physiotherapy center, Specialized physiotherapy and arthritis research center, and Unique pain and specialized physiotherapy center. The only pain medication group will be treated and follow up at Impulse hospitals limited. We are not disclosing the specification of centers for therapy group allocation to ensure the physiotherapists and the patients are blinded to group allocation. We are expecting similar baseline criteria of respondents as all of them are enrolled from Dhaka city, moreover, the block design may ensure more similarity of baseline. Collecting respondents from different centers will increase the rigor of the study and ensure that there was no cross-contamination of data.

Participants will be included in this study with (1) any two of three diagnosis criteria of CR ⁶ as (a) unilateral or bilateral radicular pain with or without neck pain, (b) paraesthesia or numbness and/or weakness, and/or altered reflex in the dermatome or myotome of cervical nerve root C2-C8, and (c) Magnetic resonance imaging (MRI) confirmed nerve root compression related with clinical findings. Other inclusion criteria include (2) CR for more than 6 months, ⁵ (3) Brief Pain Inventory (BPI) pain severity score between 1 and 6 on an 11-point scale ranging from 0 to 10, (4) age between 18 and 50 years, to avoid the degenerative changes of the intervertebral disc, and (5) male or female sex. On the other hand, participants will be excluded if (1) any medical condition prevents the application of desired treatment confirmed by a consultant physician, (2) a pathological source of pain including TB spine, spinal tumor, or abscess, (3) early spinal fracture, (4) rheumatoid arthritis or ankylosing spondylitis, (5) red flags syndrome including cervical myelopathy, (6) patient unwilling or declined to participate in either physiotherapy approaches or pain medication, (7) dropped out within the first week of inclusion.

Overall, four groups of participants will be receiving four independent treatment approaches for 4 weeks. The treatment will be provided by either McKenzie mechanical diagnosis of therapy (MDT) approach, regional approach (RA), structural diagnosis and management (SDM) approach, or only pain medication. There will be no added treatment to ensure the true effect is documented.

McKenzie mechanical diagnosis of therapy (MDT)

McKenzie MDT Cervical spine assessment, diagnosis, and treatment form of the McKenzie Institute will be used to diagnose and treat CR cases with a customized approach. The components of treatment are the findings from the assessment and test movements. The treatment team will consist of 5 physiotherapists working in the musculoskeletal area supervised by a consultant physiotherapist completing McKenzie A and B Module from the McKenzie Institute.

Regional approach (RA)

The regional approach is applied through an assessment and treatment model (Extended data 1 ³² ). The assessment model screens CR as the 1 ^st step of problems and examine the whole region of cervical, thoracic and upper limb region as 2 ^nd and 3 ^rd step. In the 4 ^th step, RA categorizes the screened impairments in a biopsychosocial model. Ra is a universal concept, the diagnosis and treatment are based on a hypothetical principle that asks for examining a region instead of any specific structures. The treatment components are basic manual therapy approaches categorized by correction of asymmetry of alignment, treatment of soft tissues, and restoration of mobility. The RA treatment team consists of 5 physiotherapists working in a musculoskeletal physiotherapy set-up supervised by another physiotherapist with a doctoral degree in evaluating RA concepts ¹³ on spinal mechanical problems.

Structural diagnosis and management (SDM)

SDM is an assessment and treatment approach for musculoskeletal problems. SDM cervical spine assessment (Extended data 2 ³² ) has 5 parts. The components consist of subjective assessment, history, pain assessment at six states, selective cervico-dorsal muscle stretch and strength test, neurological assessment of sensory and motor examination of C1- C8 nerve roots, Dural test or sign, and nerve sensitivity test. From these assessments, a provisional diagnosis of affected structures is made, and the treatment is specified according to the findings of the above assessment. This treatment is provided by a team of 5 physiotherapists supervised by two advanced practice physiotherapists with a minimum experience of 16 years in musculoskeletal physiotherapy.

Pain medication

Physicians will prescribe a wide range of medications to control pain and associated impairments as a simple analgesic as paracetamol, tramadol/paracetamol, codeine-based analgesics, non-steroidal anti-inflammatory pain medication, opioid analgesics, muscle relaxants, corticosteroids, GABA receptor agonists, neuropathic medications. ⁷ The prescribing physicians will be either an orthopedic surgeon, neurologist, neurosurgeon, general practitioner, or physiatrist.

Physiotherapy approaches will be provided once to twice a day for a maximum of 45 minutes session, 5 days a week for 4 weeks, and the pain medication will be prescribed twice or thrice a day, for 4 weeks. The intervention will be monitored through a checklist (Extended data 3 ³² ). We anticipate no major adverse effects, but a checklist will be maintained (Extended data 4 ³² ) for monitoring adverse events of the intervention.

Outcome measurement

Primary outcomes

Pain

A Brief Pain Inventory (BPI) will be the outcome measure for pain. BPI measures pain through 3 subscales covering all domains of impairments, 1) pain severity, 2) pain affective interference, and 3) pain physical interference. Pain severity is measured by a 0 to 10-point scale indicating no pain to pain as bad as can be imagined. It is calculated by the mean of four items. The pain affective interference has seven items scoring 0 to 10 and calculated through average. The pain physical interference is three items scoring 0 to 10, measuring how pain interferes with a person’s activity and livelihood. The BPI is a widely used and recommended tool for musculoskeletal neuropathic pain outcomes. ¹⁹

Range of motion

A goniometer reading will be employed to measure the range of motion (ROM) of the cervical spine. A goniometer is an instrument that measures the available range of motion at a joint. The art and science of measuring the joint ranges in each plane of the joint are called goniometry. This is a universal tool to measure ROM, also valid to measure ROM of the cervical spine. ²⁰

Disability

The neck disability index (NDI) will be used to determine disability induced by CR. The NDI is the most widely used and most strongly validated instrument for assessing self-rated disability in patients with neck pain. It has been used effectively in both clinical and research settings in the treatment of this very common problem. When measuring neck and arm pain associated with impairment in Serbian patients with cervical radiculopathy, the NDI Scale is a reliable tool. ²¹

Secondary outcome

Quality of life

World Health Organization Quality of life questionnaire (WHOQoL) brief questionnaire will be used to determine the quality of life for CR cases. The WHOQOL evaluates how people see their place in life concerning their objectives, expectations, standards, and worries as well as the culture and value systems in which they live. Over four years, it was jointly created in several centers with varied cultural backgrounds. The WHOQOL was successfully piloted on around 4500 respondents in 15 cultural contexts. The new WHOQOL Field Trial Form has been prepared and is currently undergoing field testing because of this data. The WHOQOL generates a multi-dimensional profile of quality-of-life scores across six categories and 24 sub-domains. The tool is validated for determining the quality of life in people having chronic pain. ²²

Teare and colleagues ²³ recommended a minimum of 35 cases in each group of a randomized clinical trial to obtain the precision of the pooled standard deviation and for true effect size. We will be trying to reach 160 samples in total with a minimum of 40 samples for a group.

We will perform hospital-based randomization to recruit CR patients from the population. Hospital-based randomization is a specialized process of cluster randomization. To prevent trial contamination, we will have separate centers acting as a cluster of samples. Patients attending three physiotherapy set-ups between July and December 2022 will be screened for eligibility and if recruited they will further have assigned to the specific physiotherapy treatment group by concealed allocation. The concealed allocation process for physiotherapy groups will be performed through the randomization of 120 numbers (except for the pain medication group) in Microsoft Excel software. Participants in the pain medication group will be clustered from the fourth setup (specialized hospital). After screening, the participant’s treatment center can be changed based on allocation, the centers are located in the city and have similar costs for treatment. Besides, the trial coordinator conducted written permission for the patient’s exchange. To ensure all the group’s recruitment is running with a similar nature and similar baseline criteria are being achieved, randomized block design ²⁴ for group allocation will be adopted.

The study will be followed according to the Consolidated Standards of Reporting Trials (CONSORT) guideline. The study procedure is summarized in Figure 1. After the screening, participants will be briefed about the study and a written informed consent form will be provided to the patients. After consent, four assessors from four centers will take the baseline assessment through the questionnaire. After the baseline assessment is completed, the files will be collected by the research team. Then, participants will be allocated to groups according to concealed process and respondents will be receiving interventions. After 2 weeks, participants will be contacted at their homes or feasible place to take the intermediate assessment by two blinded assessors. These two blinded assessors will also perform the post-treatment in a similar approach. The Baseline measurement includes socio-demographic and clinical information, BPI, ROM, NDI, and WHOQoL, the intermediate test includes BPI, ROM, and NDI and the post-treatment includes BPI, ROM, NDI, and WHOQoL.

All participants except the pain medication group will be blinded to the interventions. The pain medication group will be chosen according to the patient’s interest in not receiving physiotherapy despite of prescription by a physician or any health professionals. The treatment providers will be blinded to the groups, but they will be aware of the treatment of their group. As this will be a multi-center trial, participants, and intermediate and post-treatment assessors will be blinded in this study. Participants will be blinded to the group allocation but not blinded to the treatment components of their group as they will pay for the interventions. The research team will not participate in the trial execution and there will be a separate assessor, treatment provider, monitoring team, and trial manager to ensure the coordination of the trial.

A monitoring team consisting of 4 physiotherapists, who are not participating in the trial in any other duties will monitor the (1) intervention chart and (2) adverse events chart (Extended data 3 and 4 ³² ) and execute the blocking process of enrollment of the trial. They will report to the trial manager. The monitoring team will also keep the filled-up questionnaire, audit the data, and carry out any interim analysis. Any kind of changes in the methods or intervention will be reported to the IRB by the principal investigator through the monitoring team.

It is expected that the stated protocol will have no major adverse events, but if any unexpected event occurs during or after intervention this will be noted, and primarily reported to the concerned professionals by the monitoring team. The concerned therapist will note it in their Subjective, Objective, Analysis and Plan note (SOAP note) and later inform the principal investigator. Before starting treatment, the patient should be informed that if they feel pain, skin irritation, or any kind of discomfort they must report it to their physiotherapist. Any serious harmful effects will be documented and reported during the final publication of the trial.

Data will be analyzed according to its nature by SPSS version 23, and R-4.2.1 for Windows. Screening for normal distribution will be carried out by bell curve, skewness, kurtosis, Kolmogorov–Smirnov test, and Shapiro–Wilk test. Descriptive analysis will be performed using the arithmetic mean and standard deviation for continuous data, and frequency and percentage for categorical data. Baseline computability, between group intermediate and post-treatment changes among four groups, will be performed using MANOVA or Multivariate Kruskal-Wallis (MKW) test based on the distribution of data. Within-group changes among three measurements will be performed by repeated measure ANOVA or Friedman's ANOVA, and subsequent post-hoc tests will be conducted by Paired sample t-test or Wilcoxon test. For missing data, we will use the intention to treat the analysis process. The level of significance P < .05, in the case of post hoc Bonferroni correction, will be made as P < .0125.

The trial obtained ethical permission from the Institute of Physiotherapy Rehabilitation and Research of Bangladesh Physiotherapy Association (BPA) (IPRR/IRB/24/02/2022/063) on 24 ^th February 2022. Also, the trial is registered to the Clinical Trial Registry India, the primary trial site of the World Health Organization (CTRI/2022/03/040922) on 8 ^th March 2022. The researcher will abide by the Helsinki declaration as per ethical guidelines. Before enrollment, a written informed consent (Extended data 5 ³² ) will be signed by the trial participants. The participant’s participation will be voluntary, and they will have the right to withdraw from the trial at any time during the trial. The participants will be assured that participation or withdrawal from the study will not make any change to their regular treatment process. The principal investigator and data auditors will have access to the final trial dataset, after making the process anonymous, the authors will have access to the unanimous data. The investigators are independent persons to assess the patients and document in hard copies, they are contracted not to have any disclosure or access to final data. There will be post-trial care if any adverse effects are noted. As the treatment process is mainly based on exercise and manual therapy, we anticipate no serious adverse effects.

For generating the protocol, we followed Interventional Trials 2013 (SPIRIT) guidelines ( Table 1), ³² and for the RCT we will follow Consolidated statements for reporting randomized trials (CONSORT) guidelines ( Figure 1).

The trial is recruiting participants now.

After the end of the trial, a seminar will be conducted to share the results of the trial with relevant stakeholders. A research paper will be submitted to an indexed journal for publication of the original research. Besides, training sessions for physiotherapy professionals will be arranged based on the most effective treatment concept from the trial. The trial results will be published as open access to ensure the maximum visibility of the original research.