Optimizing the management algorithm for adults with functional constipation failing a fiber/laxative trial in general gastroenterology: Cost-effectiveness and cost-minimization analysis

Abstract

INTRODUCTION:

Anorectal function testing is traditionally relegated to subspecialty centers. Yet it is an office-based procedure that appears capable of triaging care for the many patients with Rome IV functional constipation that fail empiric over-the-counter therapy in general gastroenterology, as an alternative to empirical prescription drugs. We aimed to evaluate cost-effectiveness of routine anorectal function testing in this specific population.

METHODS:

We performed a cost-effectiveness analysis from the patient perspective and a cost-minimization analysis from the insurer perspective to compare three strategies: (1) empiric prescription drugs followed by pelvic floor physical therapy (PFPT) for drug failure; (2) empiric PFPT followed by prescription drugs for PFPT failure; or, (3) care directed by up-front anorectal function testing. Model inputs were derived from systematic reviews of prospective clinical trials, national cost datasets, and observational cohort studies of the impact of chronic constipation on health outcomes, healthcare costs, and work-productivity.

RESULTS:

The most cost-effective strategy was up-front anorectal function testing to triage patients to appropriate therapy, in which the subset of patients without anal hypocontractility on anorectal manometry and with a balloon expulsion time of at least 6.5 seconds would be referred to PFPT. In sensitivity analysis, empiric PFPT was more cost effective than empiric prescription drugs except for situations in which the primary goal of treatment was to increase bowel movement frequency. If adopted, gastroenterologists would refer ~17 patients/year to PFPT, supporting feasibility.

DISCUSSION:

Anorectal function testing appears to be an emergent technology to optimize cost-effective outcomes, overcoming testing costs by phenotyping care.

INTRODUCTION

Chronic constipation accounts for >2.1 million referrals to gastroenterologists and other specialists each year in the United States.¹ Many gastroenterologists regard constipation as a benign disorder of slow intestinal transit, and so the mainstay of specialty care management involves cycling over-the-counter (OTC) laxatives and reinforcing the need to increase water intake and dietary fiber.² Over one-half of patients do not respond to these interventions yet face limited choices largely due to cost.³ Specifically, conflict arises among insurers that would pay for prescription drug treatments, patients who would pay out-of-pocket for additional OTC laxatives or dietary changes, and gastroenterologists that seek to minimize unnecessary testing.⁴ Unsurprisingly, patients seeking specialty advice for chronic constipation report care dissatisfaction, high levels of healthcare utilization, and impaired quality-of-life rivaling congestive heart failure or diabetes mellitus.^2,5,6 Routine consideration for other major causes of constipation poses an opportunity to obviate these barriers.

Functional defecatory disorders are defined by abdomino-anal incoordination during defecation^7,8 and are apparently common among patients with chronic constipation seeking routine gastroenterology care.⁹ Yet dogma limits evaluation to treatment-refractory patients in subspecialty centers, for which only patients with dyssynergia qualify for intensive biofeedback on a battery of tests. It is possible that many more patients might benefit from pelvic floor therapy. In this broader context, we recently demonstrated that pelvic floor physical therapy delivered in the community is a reasonable alternative to prescription drug therapy to manage patients meeting Rome IV criteria for functional constipation that fail a low-cost trial of OTC therapy in general gastroenterology.¹⁰ And, routine anorectal function testing appears capable of predicting the likelihood of success of pelvic floor physical therapy, which is important because access to pelvic floor physical therapists can be limited.^11,12 These findings demand acceptance that the most important test parameters on anorectal function testing might reasonably differ among treatment-naïve patients receiving local pelvic floor physical therapy, compared to outcomes that should rely on dyssynergia for treatment-refractory patients receiving biofeedback. The recent American College of Gastroenterology-American Gastroenterology Guideline leveraged significant randomized control trial data comparing prescription drug therapy to no therapy^14,15, and other guidelines on benign anorectal disorders leverage randomized control trial data that evaluate intensive testing and treatment designed for use by expert centers.⁹ Meanwhile, the decision node relevant to all gastroenterologists is clearly posed in the clinical decision support tool that accompanies recent guidelines¹³ and to our knowledge remains unanswered: Should patients in general gastroenterology that fail empiric OTC therapy receive pelvic floor testing or undergo empiric prescription drug therapy?

We conducted a cost-benefit analysis from patient and insurer perspectives to determine the optimal strategy to manage patients in the general gastroenterology community that are at the point of considering prescription drug therapy. Namely, our study reflects patients that have sufficient symptom severity and have failed that fail a low-cost trial of empiric OTC laxatives or soluble fiber supplementation.

METHODS

We adapted a recently published decision-analytic model that was developed to assess costs and outcomes among patients with chronic constipation (Supplemental Figure 1). The published model developed assumptions on treatment efficacy, tolerability, and safety using the RAND/UCLA Appropriateness Method that are previously described in detail.³ This study adhered to the CHEERS checklist and methodologic guidance from the Second Panel on Cost-Effectiveness in Health and Medicine.¹⁴

Our base-case patient was a commercially-insured, middle-age individual with chronic constipation that has reached gastroenterology specialty care, meets clinical Rome IV functional constipation criteria and has failed a trial of empiric OTC therapy, is up-to-date with colon cancer screening and lacks warning signs for malignancy. Our study is not designed to imply or suggest that patients should undergo pelvic floor evaluation prior to low-cost OTC therapy. Guidelines strongly recommend that gastroenterologists advise an empirical low-cost trial of daily OTC osmotic laxatives and/or soluble fiber supplementation prior to considering more advanced forms of treatment, including pelvic floor evaluation or prescription drug therapy.^15,16

We modeled three competing strategies to managing patients failing a trial of osmotic laxatives or soluble fiber supplementation in general gastroenterology care, for whom the broadly relevant question is to define the next best step in management: (1) “status quo”: empiric trial of prescription drug therapy as first-line followed by consideration of pelvic floor physical therapy for treatment-refractory patients (noting that this status quo aligns with usual care and conflicts with guidelines advocating physiology-based management), (2) “empiric pelvic floor physical therapy”: empiric trial of pelvic floor physical therapy as first-line followed by prescription drugs for treatment-refractory patients, or (3) “testing-directed care”: care directed by up-front anorectal function testing in which patients with abnormal testing would attend pelvic floor physical therapy or with normal testing would receive prescription drugs (to test the impact of embracing a physiology-oriented management paradigm across general gastroenterology on novel squeeze profiles).

Our primary analysis considered all patients meeting Rome IV criteria for functional constipation presenting to the general gastroenterologist. Here, efficacy was defined on the most appropriate measure for each modality: for pelvic floor physical therapy, we applied a global PAC-SYM measure representative of the comprehensive constipation symptom domain; and, for drugs we applied the FDA responder endpoint that anchors on stool form and completeness of evacuation.¹⁷ To accommodate scenarios in which the patient and general gastroenterologist aimed to choose treatments based primarily on transit, we then conducted a parallel analysis among the subset of patients reporting fewer than three weekly complete spontaneous bowel movements (CSBM) at baseline. In the parallel analysis, efficacy was defined solely on improvement in weekly CSBMs (FDA responder endpoint), thereby matching traditional constructs of the transit-oriented constipation paradigm across all treatments.¹⁷

Outcomes and costs

Efficacy, tolerability, and safety were modeled on integrated clinical trials data from systematic reviews and network meta-analyses. Costs were adjusted to 2022 US dollars and sourced from national, federally-managed datasets including: the Centers for Medicare and Medical Services (CMS) National Average Drug Acquisition Cost (NADAC) database to capture average wholesale commercial drug prices¹⁸; national observational data on the added costs in a commercially insured population associated with symptomatic chronic constipation compared to an age- and sex-matched non-constipated control population¹⁹; and, observational studies evaluating work-productivity losses with symptomatic chronic constipation¹⁹. Sources for all model inputs are reported in Table 1 including previously published inputs for the original model. Costs such as childcare and transportation were included to more conservatively (and not optimistically) estimate the cost-effective benefits of pelvic floor physical therapy in light of the inherent need for office appointments.

Table 1: Model inputs.

Reproduced from the original publication for the underlying model and updated to include 2022 year costs and additional inputs for the comprehensive algorithm.³

Description	Base-case value	Min	Max	Distribution	References
Outcomes
Linaclotide 145mcg responder rate	15.6%			Beta: N=994	Shah, et al. (2018)32 Luthra, et al. (2019)33
Linaclotide 145mcg discontinuation rate	5.8%			Beta: N=994	Shah, et al. (2018)32 Luthra, et al. (2019)33
Linaclotide 72mcg responder rate	13.4%			Beta: N=411	Shah, et al. (2018)32 Luthra, et al. (2019)33
Linaclotide 72mcg discontinuation rate	2.9%			Beta: N=411	Shah, et al. (2018)32 Luthra, et al. (2019)33
Lubiprostone 24mcg responder rate	45.2%			Beta: N=239	Luthra, et al. (2019)33 FDA Technical Review34
Lubiprostone 24mcg discontinuation rate	10.7%			Beta: N=271	Luthra, et al. (2019)33 FDA Technical Review34
Plecanatide 3mg responder rate	20.7%			Beta: N=1,133	Shah, et al. (2018)32 Luthra, et al. (2019)33
Plecanatide 3mg discontinuation rate	1.7%			Beta: N=1,169	Shah, et al. (2018)32 Luthra, et al. (2019)33
Prucalopride 2mg responder rate	18.1%			Beta: N=1,237	Luthra, et al. (2019)33 FDA Technical Review35
Prucalopride 2mg discontinuation rate	6.1%			Beta: N=659	Luthra, et al. (2019)33 FDA Technical Review35
Pelvic floor physical therapy responder rate	39.6% for PAC-SYM response 12.3% for CSBM response			Beta: N=60	Shah, et al. (2022)11
Pelvic floor physical therapy discontinuation rate	11.7%			Beta: N=60	Shah, et al. (2022)11
Number of chronic constipation-related office visits per year	1.44	0	10		Taylor, et al. (2020)19
Quality-adjusted life years
Health utility associated with usual care	0.813	0.723	0.813		Parker, et al. (2011)20
Health utility associated with treatment response	0.098	0.040	0.120		Parker, et al. (2011)20
Health utility associated associated with linaclotide 145mcg	0.907			Anchored on changes in health utilities associated with treatment response in sensitivity analysis	Carson, et al. (2010)36 Parker, et al. (2011)20 Schoenfeld, et al. (2017)37
Health utility associated with linaclotide 72mcg	0.911				Parker, et al. (2011)20 Schoenfeld, et al. (2017)37
Health utility associated with lubiprostone 24mcg	0.905				FDA Technical Review34 Parker, et al. (2011)20
Health utility associated with plecanatide 3mg	0.924				DeMicco, et al. (2017)38 Parker, et al. (2011)20
Health utility associated with prucalopride 2mg	0.886				Tack, et al. (2015)39 Parker, et al. (2011)20
Costs
Cost of linaclotide 145mcg pill	$15.71	$0	$15.71		NADAC Database18
Cost of linaclotide 72mcg pill	$15.70	$0	$15.70		NADAC Database18
Cost of lubiprostone 24mcg pill	$5.95	$0	$5.95		NADAC Database18
Cost of plecanatide 3mg pill	$16.27	$0	$16.27		NADAC Database18
Cost of prucalopride 2mg pill	$15.58	$0	$15.58		NADAC Database18
Number of required physical therapy visits	3 visits	1	6		Shah, et al. (2022)11
Cost of pelvic floor physical therapy consultation (CPT 97162 or 97163)	$102.43	$0	$200		Physician Fee Schedule40 Shah, et al. (2022)11
Cost of pelvic floor physical therapy treatment visits (CPT 97140, 97110, 97112, 97530, and 97535)	$164.39	$0	$250		Physician Fee Schedule40 Shah, et al. (2022)11
All chronic constipation-related healthcare costs per year	$2,566.08	$0	$5,000		Taylor, et al. (2020)19
Work-productivity impairment due to chronic constipation	29.1%			Beta; ɑ=0.61 and ß=1.51	Taylor, et al. (2020)19
Mean annual wage	$46,800	$0	$100,000		US Bureau of Labor Statistics41
Half-day cost of childcare to attend clinic (accounting for 25% of households having children)	$14.50	$0	$14.50		US Census Bureau42 Cost of Care Survey43
Transportation to/from medical visits	$20	$0	$20		Muennig (2008)44

Clinical inputs were collated from systematic reviews and network meta-analyses and checked against primary sources including FDA multi-discipline reviews, integrated clinical trial analyses, and clinical trial reports. CPT=Computerized Procedural Terminology; CSBM=complete spontaneous bowel movement; NADAC=National Average Drug Acquisition Cost Database; PAC-SYM=Patient Assessment of Constipation Symptoms

Effectiveness

We modeled treatment effectiveness based on the increase in quality-adjusted life years (QALYs) that were associated with improved quality-of-life among patients with constipation. For prescription drugs, disease-specific quality-of-life outcomes reported in integrated clinical trial analyses and FDA technical reviews were mapped onto the valid and reliable EuroQOL EQ-5D-5L health-related quality-of-life measure that is widely used to inform QALY gains.²⁰ As with any non-lethal chronic illness, we expected that effectiveness gains would be numerically small though not clinically insignificant. For context, 0 QALYs means death and 1.0 QALY means perfect health. For example, a patient with chronic constipation that responds to treatment would have 0.05 greater QALYs at the end of one year, compared to a patient that does not respond to typical treatment. Over 20 years with disease, this would result in the equivalent of one full additional year of complete health for the patient that responds to treatment.

Analysis

Base-case analysis was performed to evaluate the one-year costs accumulated with each strategy from insurer and payer perspectives. This time horizon aligns with the usual timeframe for health plan determinations on annual deductibles, premiums, and co-pays. We assumed that incremental cost-effectiveness ratios (ICER) below a willingness-to-pay threshold of $100,000 per QALY-gained were cost-effective. Probabilistic sensitivity analysis was conducted on 100,000 simulated patients to evaluate the robustness of cost-effectiveness estimates. Recognizing our intention to evaluate overarching conceptual strategies to use pelvic floor physical therapy or prescription drugs at all, we modeled the most cost-effective prescription drug strategies in primary analysis. Comparisons among individual drugs are reported previously for subsets of patients that prefer this approach.³ Sensitivity analyses were conducted across all model input, including to evaluate the capacity of anorectal function tests to influence cost-effectiveness from a patient perspective and cost-savings from an insurer perspective. A 3% annual discount rate was applied. Analysis was performed using TreeAge Pro 2022 R2 (TreeAge Software Inc, Williamstown, MA).

RESULTS

Costs and effectiveness gains are described for each strategy in Table 2 and updated from previously reported prior-year 2021 costs.

Table 2: Cost-effectiveness of algorithmic treatment strategies for chronic constipation among patients referred to general gastroenterology that fail an initial empiric trial of osmotic laxative or soluble fiber supplementation.

Relative cost effectiveness of prescription drug or pelvic floor physical therapy strategies depend on the primary goals of treatment and likelihood of treatment success.

Strategy	Total cost ($/year)	Total effectiveness (QALY gained/year)	Incremental cost ($)	Incremental effectiveness (quality adjusted life year or QALY)	Incremental cost-effectiveness ratio or ICER ($/QALY-gained)
Insurer perspective
Continued usual care (rotating over-the-counter products and dietary advice)	$2,566	0.813	Reference	Reference	Reference
Empiric pelvic floor physical therapy for patients with infrequent hard/lumpy stools that primarily seek improvement in CSBM frequency*	$2,583	0.821	$17 additional cost	+0.008	$2,173/QALY-gained compared to usual care
Empiric prescription drug**	$7,146	0.832	$4,580 added cost	+0.019	Dominates usual care $429,430/QALY-gained compared to empiric pelvic floor physical therapy for patients that primarily seek improvement in CSBM frequency
Empiric pelvic floor physical therapy for patients that meet Rome IV functional constipation criteria that seek global symptom improvement*	$1,964	0.838	$602 saved	+0.025	Dominates usual care and empiric prescription drug
Care directed by up-front laboratory-based anorectal function testing for appropriate patients that meet Rome IV functional constipation criteria*** (AGA/ACG guideline recommendation)	$1,350	0.856	$1,216 saved	+0.043	Dominates all empiric strategies
Patient perspective
Continued usual care (rotating over-the-counter products and dietary advice)	$13,761	0.813	Reference	Reference	Reference
Empiric pelvic floor physical therapy for patients with infrequent hard/lumpy stools that primarily seek improvement in CSBM frequency*	$11,293	0.821	$2,468 saved	+0.008	Dominates usual care
Empiric prescription drug**	$9,607	0.832	$6,154 saved	+0.019	Dominates usual care and empiric pelvic floor physical therapy for patients that primarily seek improvement in CSBM frequency
Empiric pelvic floor physical therapy for patients that meet Rome IV functional constipation criteria that seek global symptom improvement*	$7,971	0.838	$5,790 saved	+0.025	Dominates usual care and empiric prescription drug
Care directed by up-front laboratory-based anorectal function testing for appropriate patients that meet Rome IV functional constipation criteria*** (AGA/ACG guideline recommendation)	$4,684	0.856	$9,077 saved	+0.043	Dominates all empiric strategies

^*Strategies involving pelvic floor physical therapy apply only to patients with dominant bowel or rectal symptoms, as opposed to abdominal sensory complaints as dominant symptoms. Strategies involving pelvic floor physical therapy are only applicable to patients that are interested in this treatment modality and that are appropriate candidates in the judgment of the patient and managing physician.

^**For the purposes of modeling, prucalopride was the most cost-effective/cost-saving drug at a willingness-to-pay threshold of $100,000/QALY-gained. The intention of this model is to consider the choice to use prescription drugs at all and to defer individual prescription drug choices to the patient and physician based on available rebates and formulary availability informed by previously published analyses.

^***This analysis was restricted to the subgroup of patients with the greatest likelihood of clinical response identified on laboratory-based anorectal function testing that lack anal hypocontractility defined by the London consensus. On 3D-high definition anal manometry equipment (Medtronic, Minneapolis, MN, USA), this subgroup corresponds to a maximum squeeze pressure of at least 192.5mmHg. This definition was developed in a recent prospective clinical trial anchored on understanding the optimal predictors of treatment response in community settings.

Cost-effectiveness and cost-savings of empiric pelvic floor physical therapy or empiric prescription drug therapy for patients failing a trial of osmotic laxatives and/or soluble fiber

The Rome IV criteria broadly define functional constipation based on having least two symptoms of: straining, sensation of incomplete evacuation, sensation of anorectal obstruction/blockage, needing manual maneuvers to defecate, lumpy/hard stools, and infrequent stools (fewer than three weekly spontaneous bowel movements). For these patients, the empiric pelvic floor physical therapy strategy would be more cost-effective and cost-saving compared to the status quo strategy of empiric prescription drugs from both patient and payer perspectives, respectively, if the primary treatment goal anchors on achieving composite improvement in abdominal, rectal, and bowel symptoms (Figure 1). This empiric strategy assumes broad availability of local pelvic floor physical therapy expertise, which may not reflect local practice settings.

Figure 1: Cost-effectiveness of routine chronic constipation strategies in general gastroenterology.

Analyses are presented from insurer perspectives (panel A) and patient perspectives (panel B). Management approaches incorporating patient needs/preferences and physiologic testing inform cost-effective care.

Following a traditional transit-oriented paradigm, the subset of patients with fewer than three weekly CSBMs may desire to improve CSBM frequency as a primary treatment goal. This logic follows the recommended design of FDA-regulated drug trials. For these patients, the status quo strategy of empirically prescribing prescription drugs for chronic constipation was more cost-effective from a patient perspective but more expensive from a payer perspective compared to an empiric pelvic floor physical therapy strategy (Figure 1).

Routine, up-front anorectal function testing with anorectal manometry and traditional balloon expulsion is on cost-effective/cost-saving algorithmic care for chronic constipation

Referring patients on the basis of routine, up-front anorectal function testing (a testing-directed care strategy) would optimize limited pelvic floor physical therapy resources toward patients that are likely to achieve the greatest cost-savings and clinical benefit. (Figure 2). Patients that did not have anal hypocontractility as a major motility disorder according to the London consensus (defined by a squeeze pressure > 192.5 mmHg on at least one of 3 attempts) had the greatest likelihood of clinical response (66.7% expected likelihood of response) compared to other definitions for test interpretation in a recent prospective clinical trial. An estimated 28.8% of patients that undergo anorectal manometry would have meet this definition and subsequently be referred to pelvic floor physical therapy (15 of 52 patients in the intention-to-treat analysis in the underlying clinical trial).

Figure 2: Sensitivity analysis on treatment preferences that maximize cost-savings to insurers by varying the expected clinical response to pelvic floor physical therapy.

Anorectal function testing appears capable of stratifying patients to the optimal treatment based on expected cost-savings to insurers. 3D-HDAM: high-definition anal manometry (Medtronic, Milwaukee, WI, USA). BET: balloon expulsion test (Mui Scientific, Mississauga, Ontario, Canada). PT: physical therapy.

From a patient perspective, the status quo strategy of empiric prescription drugs would be more cost-effective than an empiric pelvic floor physical therapy strategy, if the expected likelihood of meaningful clinical response with pelvic floor physical therapy were below 26%. The empiric pelvic floor physical therapy strategy would be more cost-effective than the status quo strategy of empiric prescription drug, if the expected likelihood of meaningful clinical response with pelvic floor physical therapy were above 26%. Anorectal manometry was not sufficient to change treatment preferences from a patient perspective according to this threshold, because the expected likelihood of clinical response with pelvic floor physical therapy remained above 26% regardless of test result. In other words, an empiric pelvic floor physical therapy strategy remained the preferred cost-effective treatment option to patients regardless of anorectal manometry finding.

Balloon expulsion testing was able to stratify patients across this threshold to identify the subset of patients with a likelihood of clinical response less than 26% (expulsion time < 6.5 seconds). The expected frequency of an abnormal balloon expulsion test would be 7.6% according to this definition (four patients of 52 in the intention-to-treat analysis in the underlying clinical trial). These findings were stable across contemporary willingness-to-pay thresholds in standard probabilistic sensitivity analyses that are designed to account for variation in population sizes and point estimates for model inputs in underlying clinical trials (Supplemental Figures 2–3).

Determinants of treatment preference in sensitivity analysis

The major determinant of cost-effective treatment preference from patient and payer perspectives was likelihood of clinical response to pelvic floor physical therapy, which can be guided by anorectal function testing (Figure 3). Other clinical outcomes, such as expectations on treatment outcomes with individual prescription drugs or constipation disease severity (defined as the impact of constipation on overall health-related quality-of-life), did not significantly impact findings (Supplemental Figures 4–5 for multiple one-way sensitivity analyses across model inputs). From a patient perspective, the status quo strategy of empiric prescription drugs would be preferred (1) among patients that experience lower impact of constipation disease severity on take-home pay and (2) among patients that do not work for pay.

Figure 3: Sensitivity analyses show that expected clinical response to pelvic floor physical therapy is the most important determinant of cost-effective treatment choice from a patient perspective.

Pelvic floor physical therapy was generally more cost-effective than prescription drugs from an insurer perspective, but this assumes clinical appropriateness of the intervention and appropriate screening.

DISCUSSION

We evaluated whether anorectal function testing to triage patients to up-front pelvic floor physical therapy would be cost effective for patients with chronic constipation that see a general gastroenterologist, fail a standard trial of low-cost osmotic laxative or soluble fiber supplementation, and meet Rome IV criteria for functional constipation. An algorithmic testing-directed care strategy employing routine, up-front anorectal function testing optimizes pelvic floor physical therapy utilization for the subset of patients that are most likely to achieve health benefits and cost-savings to themselves and their insurer (Figure 4). If routine anorectal function testing were adopted, an average gastroenterologist that sees 1,000 new consultations annually could anticipate to refer 17 patients to a local pelvic floor physical therapist each year, given that chronic constipation comprises ~6% of typical gastroenterology referral volume and that recent data suggest ~30% of patients that reach general gastroenterology, fail a trial of OTC therapy, and meet Rome IV functional constipation criteria will have an abnormal anorectal function test.^1,11 This finding strongly supports feasibility in practice.

Figure 4: Optimized cost-effective and cost-saving treatment algorithm for chronic constipation in general gastroenterology.

Up-front screening questions to ascertain appropriateness of pelvic floor physical therapy were incorporated into clinical trials data that support this model and are therefore necessary to reproduce similar results.

Constipation is broadly stratified into two basic etiologies of recto-anal evacuation disorders and slow intestinal transit.²¹ Pelvic floor physical therapy aims to improve functional evacuation disorders, while prescription drugs aim to improve intestinal transit. If the treatment goal is primarily to improve intestinal transit among patients complaining of infrequent CSBMs, then prescription drugs appear to be more cost-effective for that subset of patients. If the treatment goal is to improve global abdominal, rectal, and bowel symptoms among patients experiencing a global set of symptoms consistent with Rome IV criteria, then empiric pelvic floor physical therapy appears more cost-effective and cost-saving for that subset of patients. However, individual symptoms are poorly predictive of clinical outcomes with pelvic rehabilitation both for treatment-naive¹⁰ and treatment-refractory²² patients.

The American College of Gastroenterology and American Gastroenterological Association published new practice guidelines relevant to pharmacologic chronic constipation management.^15,16 The scope of these guidelines was to rigorously evaluate evidence for pharmacological treatment compared to no treatment. The clinical decision support tool accompanying this guideline recommended consideration of pelvic floor evaluation before prescribing prescription drugs, considering drug costs beyond the scope of the guideline itself. This contrasts to prior guidelines that advised anorectal function testing for treatment-refractory patients, implied to be after exhausting all treatments including prescription drugs based on the design of supporting randomized clinical trials. What is lost in this conversation is that both answers may be correct: (1) cost is critical in general gastroenterology considering the large number of patients, and (2) the paradigm and positioning of pelvic floor evaluation and management in general gastroenterology does not inherently need to match that of a handful of subspecialty motility centers that can safely continue to rigorously advocate extensive testing and intensive biofeedback for their subgroups of patients.^23–25 Indeed, the reality that drug trials actually enrolled relatively treatment-naïve patients is frequently lost, because the use of prescription drugs is sensibly restricted to truly treatment-refractory patients out of concern for costs in the minds of gastroenterologists that decline to prescribe expensive drugs to many millions of treatment-naïve patients.^2,3 Therefore, our study is the first to support the robustness of this clinical decision support tool¹³ that provides a way out for the many patients caught “in the middle” between evidence and cost—that is to say, the actual evidence base developed across clinical drug trials and our recent pelvic floor trial for patients that reach a general gastroenterologist, meet Rome IV criteria, and fail a low-cost OTC trial.¹¹

Anorectal manometry combined with balloon expulsion testing appears sufficient to triage patients that reach general gastroenterology and fail an OTC trial to the most cost-effective treatment.¹¹ Such predictive capacity relies on squeeze parameters and balloon expulsion times, as opposed to relying on traditional rectoanal profiles of dyssynergic defecation. These parameters are included in standard assessments and are directly and numerically captured from existing anorectal manometry software across manufacturers without relying on physician interpretation according to expert consensus.^8,26 Despite insurer reimbursement, current technology demands dedicated personnel, physical space, and capital expenditure that may also limit broad adoption.²⁶ Advances in anorectal function assessment including investigational point-of-care testing options may further shift the cost-effective care model in favor of using up-front testing to direct therapy and candidate selection that are needed to facilitate broad adoption in general gastroenterology.^27,28

Discussing the nature of constipation treatment options is an important first step prior to any anorectal function testing, so that patients are able to align with the single most compatible treatment at the outset. Compared to daily medication or laxative routines, patients who pursue pelvic floor physical therapy must be willing to undergo rectal examination/therapy and to dedicate time. As demonstrated by Rao, et al. commitment to biofeedback as a core of pelvic floor physical therapy results in sustained clinical response.²⁹ In fact, the time investment to undergo pelvic floor physical therapy should be balanced against the potential work-productivity gains associated with treatment response. Our findings suggest that work-productivity loss due to constipation is an important factor from a patient perspective, which can relate to prolonged toileting rather than absence from work especially among patients that reach a gastroenterologist in their care journey, fail OTC therapy, and meet Rome IV functional constipation criteria. Based on our model assumptions of high work-productivity impairment, many patients that are not significantly impacted by constipation may find pelvic floor physical therapy (and testing for evacuation disorders) less relevant to their care.

Our findings are relevant to the many patients with constipation symptoms that are not significantly affected by disorders of gut-brain interaction. Prior to enrolling in the underlying clinical trial providing data for this study, patients were asked two questions in routine care. First, is abdominal pain the prevailing symptom? If so, the patient was triaged toward treatments for disorders of gut-brain interaction rather than evaluating the pelvic floor.³⁰ Second, does pelvic floor physical therapy sound reasonable, or would you like to try a different form of therapy?³¹ As a result of this process, patients in our general gastroenterology practice who chose anorectal function testing and pelvic floor management had 88.3% adherence, no measurable clinical depression or anxiety, and no demonstrable association between low levels of gastrointestinal symptom-specific anxiety and clinical outcome.

Inherent limitations of our study design should be considered. First, our findings do not compete with dogma. For treatment-refractory patients in subspecialty centers, evidence-based protocols anchor on the presence of dyssynergic defecation on at least 2 of 3 anorectal function tests to identify patients for intensive biofeedback.⁹ Instead, our findings apply to the many patients that otherwise continue to receive rotating empirical advice even after meeting Rome IV criteria and failing an obviously low-cost initial trial of empirical OTC therapy just as recommended in guidelines.² Second, incorporating pelvic floor physical therapy into routine practice demands availability. This is mitigated by our finding that the average gastroenterologist could anticipate to refer only ~17 patients per year to pelvic floor physical therapy in light of the increasing number of availability of this specialty in many communities, such as across rural northern New England. Third, our findings should not be used to limit prescription drug availability by insurers, because acceptance of pelvic floor physical therapy depends on a conversation with the patient rather than a requirement based on a test or insurance carrier.¹⁰ Finally, the relative size of pelvic floor physical therapy clinical trials is generally small. Yet, trials of similar sample size are accepted as the basis for recent clinical practice guidelines that advocate consideration for pelvic floor disorders.⁹ We mitigated this common limitation to all behavioral intervention trials using standard probabilistic sensitivity analyses and extensive sensitivity analyses on model inputs.

In summary, the optimal algorithmic approach to chronic constipation should begin with a conversation on appropriate management options. Our findings suggest that these options could include a trial of up-front pelvic floor physical therapy, which while may be perceived as provocative, is safe. Our findings suggest that routine anorectal function testing in general gastroenterology is indeed less expensive than routinely and empirically prescribing prescription drugs to all patients.³ Patients who express interest in pelvic floor physical therapy can then undergo anorectal function testing to ensure physiologic appropriateness considering limited physical therapy resources and patients’ time. Such an approach holds the promise of improving clinical outcomes and costs for one of the most common reasons for referral to the general gastroenterologist.

Study Highlights.

WHAT IS KNOWN

• Anorectal function testing is a brief, safe, office-based procedure capable of identifying pelvic floor dysfunction. Yet it is traditionally relegated to subspecialty centers.

• Meanwhile, over two million patient see U.S. general gastroenterologists for constipation annually. One-half of patients report dissatisfaction and/or non-response to rotating, empirical laxative treatments without anorectal function testing in usual care.

• The cost-effectiveness of a paradigm to offer up-front anorectal function testing after an initial fiber/laxative trial in general gastroenterology is unknown.

WHAT IS NEW HERE

• Anorectal function testing appears cost-effective and cost-saving compared to prescription therapy among patients in general gastroenterology that fail a trial of fiber/laxatives, because health gains and downstream cost savings with phenotype-guided testing outweighs up-front testing costs.

• Abnormal anorectal function testing identifies patients that benefit from community-based pelvic floor physical therapy.

• Normal anorectal function testing identifies patients that benefit from intensifying the medical regimen.

• If adopted, the general gastroenterologist would expect to refer 17 patients per year to a local pelvic floor physical therapist, supporting feasibility in practice.

• Our findings support the emergence of anorectal function testing technology and practice that is currently limited to specialty centers.