Towards an optimal therapy strategy for myogenous TMD, physiotherapy compared with occlusal splint therapy in an RCT with therapy-and-patient-specific treatment durations

Background Temporomandibular Disorders (TMD) may be characterized by pain and restricted jaw movements. In the absence of somatic factors in the temporomandibular joint, mainly myogenous, psychobiological, and psychosocial factors may be involved in the aetiology of myogenous TMD. An occlusal appliance (splint) is commonly used as a basic therapy of the dental practice. Alternatively, a type of physiotherapy which includes, apart from massage of sore muscles, aspects of cognitive-behavioural therapy might be a basic therapy for myogenous TMD. Treatment outcome of physiotherapy (Ph-Tx) was evaluated in comparison to that of splint therapy (Sp-Tx), using the index Treatment Duration Control (TDC) that enabled a randomized controlled trial with, comparable to clinical care, therapy-and-patient-specific treatment durations. Methods Seventy-two patients were randomly assigned to either Ph-Tx or Sp-Tx, with an intended treatment duration between 10 and 21 or 12 and 30 weeks respectively. Using TDC, the clinician controlled treatment duration and the number of visits needed. A blinded assessor recorded anamnestic and clinical data to determine TDC-values following treatment and a 1-year follow-up, yielding success rate (SR) and effectiveness (mean TDC) as treatment outcomes. Cohen’s d, was determined for pain intensity. Overall SR for stepped-care was assessed in a theoretical model, i.e. a second of the two studied therapies was applied if the first treatment was unsuccessful, and the effect of therapy sequence and difference in success rates was examined. Results SR and effectiveness were similar for Ph-Tx and Sp-Tx (long-term SR: 51–60%; TDC: −0.512– −0.575). Cohen’s d was 0.86 (Ph-Tx) and 1.39 (Sp-Tx). Treatment duration was shorter for Ph-Tx (on average 10.4 weeks less; p < 0.001). Sp-Tx needed 7.1 less visits (p < 0.001). Conclusions Physiotherapy may be preferred as initial therapy over occlusal splint therapy in stepped-care of myogenous TMD. With a similar SR and effectiveness, physiotherapy has a shorter duration. Thus patients whose initial physiotherapy is unsuccessful can continue earlier with subsequent treatment. The stepped-care model reinforces the conclusion on therapy preference as the overall SR hardly depends on therapy sequence. Trial registration isrctn.com/ISRCTN17469828. Retrospectively registered: 11/11/2016 Electronic supplementary material The online version of this article (doi:10.1186/s12891-017-1404-9) contains supplementary material, which is available to authorized users.

Enhancements of 35.0% and 40.0% in mean TDC-values (TDC less negative, a second therapy is then less effective than splint therapy) are equivalent to a reduction of 25.5% and 29.7% respectively of the difference between scores from a single variable, like 'pain intensity', between the start of treatment and the last post-treatment measurement (see below). Reductions of 35% and 40.0% in mean TDC-values (TDC more negative, a more effective second therapy) are equivalent to an enhancement of 19.7% and 22.2% of the difference in scores of 'pain intensity', before and after treatment. Hence, the power of the present study was sufficiently large for detecting fairly small inter-therapy differences in effectiveness.
As an example of the calculation of the equivalence between an enhancement in TDC and a reduction in the difference in values of 'pain intensity': the mean TDC-value of splint therapy (reference of effectiveness) is -0.575 (cf. Results, Table 3 For a post-hoc power assessment of a detectable treatment effect on the difference from single scores of pain intensity which were actually obtained (cf. Results, Table 4), individual difference values were considered between the last post-treatment measurement and the start of treatment. Considering the number of 35-37 included patients, a mean difference value of 27.7 scale-% for the entire group of splint therapy and a common SD value of 24.4 for physiotherapy and splint therapy, this study has 39% power at a level of 5% type I errors to detect an intertherapy difference of 35.0% in the mean difference value of pain intensity, and 80% power to detect a difference of 58.4%.
Considering the exchange rates between changes in TDC-values and changes in difference values from 'pain intensity' before and after treatment (see above), the power is larger for TDC-values (a multidimensional variable) than for differences in the actual scores of pain intensity (a unidimensional variable). Two-way ANOVA (p-values/significance levels, NS, non-significant) with the factor therapy (unpaired observations, 2 levels), and procedure stage (paired observations, 3 levels). Stages: the initial visit, the start of treatment (start-Tx) and the last post-treatment measurement of pain intensity (LM).

Rules for progressing and ending splint therapy
1) The intended visit program includes maximally 5 visits (including the start visit, week 0) with intervals of 6 weeks and minimally 2 visits. The intended maximal duration of wearing a splint each night is thus 24 weeks while the intended minimal duration of wearing is 6 weeks.
TDC is determined by the clinician at each possible visit, first to decide when the splint can gradually been withdrawn (paragraph 2), and second to regard the progress of treatment.
If TDC is > -0.212 following the first 3 visits, treatment with a splint is ended because the patient is not sufficiently responsive (paragraph 3).
If following 3 visits or more, TDC is ≤ -0.379 (reaching functional status) at two successive visits and the discrepancy rule † does not apply, treatment is ended as being potentially successful (paragraph 4).
If -0.379 < TDC ≤ -0.212, a patient is sufficiently responsive, and treatment is continued if the preset maximal number of 5 visits is not exceeded. If the maximal number of 5 visits is reached, treatment is finished (paragraph 5). Patients whose treatment is ultimately considered by the clinician as being potentially successful or unsuccessful, are transferred to the assessor for blinded evaluation and the decision regarding treatment success for the randomized controlled trial; 2) Withdrawal of wearing the splint can start at the 2 nd visit (week 6) § or at a later visit if TDC ≤ -0.379 and the discrepancy rule † does not apply. This withdrawal has a total duration of 6 weeks and is gradually carried out (week 1, 1 night less wearing; week 2, 2 nights less etc.). If the patient's status appears to have worsened above the upper limit of functional status (TDC>-0.379) following 6 weeks of withdrawal, full wearing is resumed for the next 6 weeks; 3) If at the 3 rd visit or at a later one (week 12 or later) the patient's responsiveness to treatment is insufficient (TDC > -0.212), the patient is asked for compliance of splint wearing. If compliance is sufficient or cannot be fulfilled, splint treatment is then ended as potentially being unsuccessful; 4) At the 3 rd visit or at a later one (week 12 or later), patients might have a functional status at this visit and the previous one (i.e. TDC≤ -0.379 and no application of the discrepancy rule † for a period of 12 weeks). Furthermore withdrawal of the splint will have been completed at this stage (paragraph 2). Treatment of these patients is then ended as being potential successful; 5) At the 5 th visit (week 24), treatment is ended for the remaining patients. The clinician determines the patient's status and decides as follows: *If the patient has functional status (TDC≤ -0.379 and no application of the discrepancy rule † ) while withdrawal of the splint (paragraph 2) is completed, treatment is considered as being potentially successful; *If the patient has functional status while the patient is still wearing the splint, the withdrawal process is started and controlled 6 weeks later (additional 6 th visit of the program, at week 30). If the patient has still functional status, the treatment is considered as being potentially successful. If the patient's status has worsened following withdrawal, treatment is considered as being potentially unsuccessful; *If the patient has not attained functional status (TDC > -0.379), treatment is considered as being potentially unsuccessful. § Each visit is related to a week number with respect to the start of treatment (1 st visit of treatment, week 0). † The following option has been added to the procedures of TDC-outcome to comply with usual clinical care and for ethical reasons. The patient's opinion as reflected in anamnestic items on daily functioning of the oral system was given priority in the treatment outcome if the index of overall relative change (including changes related to items from clinical tests) indicated a 'successful' treatment while the anamnestic items alone indicated an 'unsuccessful' treatment. To that end, the following 'discrepancy rule' was applied to the decisions of the clinician as well as conclusions of the investigator based on the data from the assessor. If the overall TDC was ≤ -0.379 (successful treatment), but TDC-anamnestic-items was >-0.212 (treatment with insufficient effect according to the patient), the treatment was considered as unfinished or, if further continuation of the treatment was not possible, the treatment was considered as being unsuccessful. The discrepancy rule was only occasionally applied, i.e.
in 2.9 % of the patients (1 out of 35) with splint therapy.

Rules for progressing and ending physiotherapy
1) The intended visit program includes maximally 15 visits (including the start visit, week 0) with intervals of 0.5 -6 weeks and minimally 10 visits. The maximal duration of physiotherapy is 21 weeks while the minimal duration is 10 weeks. Patients whose treatment is ultimately considered by the clinicians (physiotherapist and responsible dentist) as being potentially successful or unsuccessful, are transferred to the assessor for blinded evaluation and the decision regarding treatment success for the randomized controlled trial; 2) The maximal treatment program includes stage (i) a start visit (week 0) with only intake for physiotherapy, and stage (ii), 6 visits with a frequency of 2 visits/week, thus 3 weeks in total, during which exercises are instructed to be carried out at home and their performance is controlled during the visits. At the end of stage (ii) (week 3) the physiotherapist determines TDC. For patients of the maximal program, treatment will not be successful (-0.379 < TDC ≤ -0.212 or TDC ≤ -0.379 but the discrepancy rule † does apply). Treatment is then continued with stage (iii), 6 visits with a frequency of 1 visit/week during which the performance is controlled of specific exercises which have been carried out at home (end of this stage at week 9). Furthermore the physiotherapist determines TDC at each visit of stage (iii) with the conclusion of a non-successful treatment for patients of the maximal program. Stage (iii) is followed by stage (iv), 2 visits within a week in which the patient's status is subsequently determined by the clinician (the physiotherapist) and the dentist who is responsible for the patient (week 9-10). With a non-successful treatment at stage (iv), either according to the physiotherapist and/or the responsible dentist, stage (iv) is followed by stage (v), a final period of 6 weeks during which specific exercises are carried out at home.
Stage (v) is followed by stage (vi), two visits within a week for determining the patient's status by the physiotherapist and the dentist respectively (end at week 21).
Patients from the maximal program might then have a potentially successful treatment (TDC ≤ -0.379 and the discrepancy rule † does not apply) according to the physiotherapist as well as the dentist. However, regardless of treatment outcome from the clinicians at stage (vi), the patients are then referred to the blinded assessor; 3) The minimal program includes the components under (i), (ii) and (iv), with specific exercises carried out at home between stage (ii) and (iv), however without intermediate visits for control. TDC is determined by the clinician (physiotherapist) at the start visit, at the end of stage (ii) (week 3), and 6 weeks later at stage (iv) (week 9 for the minimal program rather than week 15 for the maximal program). For the minimal program, the outcome of the TDC-procedure will always be TDC ≤ -0.379 and the discrepancy rule † does not apply. At stage (iv), TDC is also determined by the dentist who is responsible for the patient.

A stepped-care model including two possible therapies
Suppose that a trajectory of stepped-care consists of a first type of therapy 'A', which if unsuccessful, is followed by a second type of therapy 'B'. The number of patients for which therapy A is successful (n A,S ) is given by: (1)) in which n T is the total number of patients in the trajectory and f A,S is the fraction of patients for which therapy A is successful (success rate as a fraction = percentage SR/100).The number of patients for which therapy A is unsuccessful (n A,U ) is then given by: (1-f A,S ) (equation (2)) Therapy A is followed by therapy B for these patients and the number of patients for which this subsequent therapy B is successful (n B,S ) is given by: n B,S = n A,U .f B,S .m (equation (3)) in which f B,S is the fraction of patients for which therapy B is successful if this therapy were applied separately (thus without a preceding therapy A, yielding the 'basic' fractional success rate), and m is a modulation factor which describes the possible influence of a preceding therapy A on the basic success rate of therapy B (m≥0).
A value of m=0 means that all patients whose treatment was unsuccessful following the first therapy A will also have an unsuccessful treatment with the subsequent therapy B. A value of m=1 means that an unsuccessful preceding therapy will not influence the basic success rate of the subsequent therapy. Values of m between 0 and 1 (0 < m < 1) indicate a diminished success rate of the subsequent therapy. This diminishing may occur if following unsuccessful treatments, patients remain who are less or more slowly responsive to any subsequent therapy. The success rate of a subsequent therapy may be enhanced, thus m > 1, if the initial therapy A starts a process of improvement which is continued and enhanced by a subsequent therapy B. When this improvement is continued in a slowly responsive patient, functional status may be attained, merely by a longer treatment duration following two  (5)).
The success rate (SR tr ) expressed as a percentage of the patients whose trajectory is successful If m=1, equation (5) reduces to:

(n A,S + n B,S )/n T = f A,S + f B,S -f A,S .f B,S
(equation (7)), and the success rate (SR tr ) expressed as a percentage of the patients whose trajectory is successful (= [(n A,S + n B,S )/n T ).100] %) is then given by: .100 % (equation (8)) The terms f A,S and f B,S can then be interchanged in the sum part as well as in the product part of equation (7) or equation (8) without influencing the outcome for the overall success-rate of the entire therapy trajectory. Hence, with a reversed sequence of possible therapies in the alternative trajectory, i.e. starting with therapy B followed by therapy A when therapy B is unsuccessful, equation (7) can then be rewritten as: (n B,S + n A,S )/n T = f B,S + f A,S -f B,S .f A,S , without changing the outcome.
Thus from equation (7) or equation (8) it follows that in the absence of a net effect of a preceding therapy on the success rate of a subsequent therapy (m=1), the success rate of the entire trajectory will not depend on the sequence in which the two types of therapies are applied. This invariance of sequence of application will occur regardless of a possible difference in the basic success rate between the two therapies. As an example, suppose that the success rate is 70% for therapy A and 50% for therapy B. The overall success rate of a trajectory that starts with therapy A followed by therapy B when therapy A is unsuccessful, is then 85% according to equation (8). This overall success rate will also occur with a reversed sequence of possible therapies in the alternative trajectory, i.e. starting with therapy B followed by therapy A when therapy B is unsuccessful.
If the success rate of a subsequent therapy is decreased following the application of an unsuccessful preceding therapy (m<1), the overall success rate of a trajectory will depend on the sequence of application of the two therapies. The largest overall success rate will then occur in that trajectory in which the starting therapy has the largest basic success rate (equation (5)). Under the assumption of identical m-values regardless of therapy sequence in a trajectory (which is plausible for therapies of which the success rates, although not identical, are similar when applied separately), the overall fractional success rate in a trajectory with reversed therapy sequence is given by: (n B,S + n A,S )/n T = f B,S + m.f A,S -m.f B,S .f A,S (equation (9)) The difference in overall success rate between two trajectories with reciprocal therapy sequences follows from subtraction of equation (5) with equation (9); this difference, denoted by ∆, is given in an absolute sense by: (10)) in which (f A,S -f B,S ) corresponds with the difference in basic fractional success rate when both types of therapies are applied separately. When (f A,S -f B,S ) is denoted as ∆ 0 , equation (10) can be rewritten as:
As an example, with a basic fractional success rate of 0.70 for therapy A and 0.50 for therapy B, the difference in success rate is 0.20 (20%) when both therapies are applied separately. Suppose that only half of the basic success rate of a therapy is realized when this therapy occurs as the second one in a trajectory of two therapies, thus the value of the modulation factor m equals 0.50. The difference in overall success rate between the two trajectories with reciprocal therapy sequences (0.10; 10%; equation (11)) will then be halved with respect to the difference in separate success rate (0.20; 20%).
If the success rate of a subsequent therapy is increased (m>1), the difference ∆ in overall fractional success rate between two trajectories with reciprocal therapy sequences is also given by equation (11). From equation (11) it follows that for the range of m-values given by 1<m≤2, the ∆-value is, like for the range 0<m<1, also smaller than the difference in basic success rates, ∆ 0 . In contrast to the range of 0<m<1, the largest overall success rate of the trajectory will occur for 1<m≤2 when this trajectory is started with the therapy which has the smallest rather than the largest basic success rate.