‘Amang’ Rodriguez Memorial Medical Center

Sumulong Highway, Marikina City

Department of Family and Community
Medicine

Journal Appraisal on Therapeutics:

Use of Probiotics in Patients with
Functional Constipation
LOUIJE P. MOMBAEL
ARMMC - POST GRADUATE INTERN
 GENERAL OBJECTIVE

• To present a journal appraisal on the use of Probiotics in Patients with

Functional Constipation using Evidence Based Medicine.
SPECIFIC OBJECTIVES

• To present data on patients diagnosed with Functional Constipation

• To guide the viewers on how resources are selected using online
research database
• To appraise the evidence for its reliability, validity, and applicability
• To integrate the evidence with the clinical expertise, patient
preference and apply it to practice
 Patient M.H.C.; 34 years old / Female
Came on consult due to difficulty of defecating for 2 weeks
Case Scenario:
• Patient had difficulty of defecation, described as hard and decrease in amount of stools.
• Took Biofit which helps on her defecation.
2 weeks • No other symptoms like abdominal pain, vomiting, fever.
• No medications taken. No consult done
PTC

• Still with above symptoms

• Now with sudden onset of left lower abdominal pain described as colicky, non-
1 week radiating and pain scale of 4-5.
PTC
• No meds taken. No consult done

Usual food intake: rice and meat (pork or beef) with 2-3 times of vegetables

Past Medical Hx / Family Medical Hx / Personal & Social Hx: UNREMARKABLE

She asked why does she need to take Probiotics.

Rationale of the Case:

• Functional constipation is a prevalent, burdensome gastrointestinal

disorder whose treatment remains challenging.
• Lately, probiotics have been adopted as an adjunct approach to
normalize intestinal transit time and alleviate symptoms.
Anatomy of Clinical Question

PICOM
Patient Patient with Functional Constipation
Intervention Probiotics
Comparison Without Probiotics
Outcome Normalize bowel function
Methodology Randomized controlled trials
Dilemma

• Among patients with Functional Constipation, how effective is the

use of Probiotics in faster normalization of stool frequency and
consistency.
What type of study is best suited for the case?

TYPE OF QUESTION SUGGESTED BEST TYPE OF STUDY

Therapy RCT > Cohort > Case Control > Case Series
Diagnosis Cross Sectional > Prospective, blind comparison to gold standard
Etiology / Harm RCT > Cohort > Case Control > Case Series
Prognosis Cohort study > Case Control > Case Series
Prevention RCT > Cohort study > Case Control > Case Series
Cost Economic Analysis
Acquiring the evidence

Appraising the evidence

Applying the evidence

Acquiring the evidence: PUBMED

“Probiotics”
25,332 results
Acquiring the evidence: PUBMED

“Probiotics”
and
“Functional
Constipation”
93 results
Acquiring the evidence: PUBMED

“Probiotics”
and
“Functional
Constipation”
Free full text , RCT, 5 years
4 results
Acquiring the evidence: PUBMED

f o r
c e
l al
r i
t ais
A pr
ap
Acquiring the evidence

Appraising the evidence

Applying the evidence

Evidence-based Family and Community Practice

• Is it relevant?
• Is it valid?
• What are the results?
• Is it applicable to my patient?
Is it relevant?

PICOM CLINICAL DILEMMA STUDY

Healthy adults aged 18 to 65 years
Patient 34/F with functional constipation with symptoms of functional
constipation
Intervention Probiotics Probiotics
Comparison Without Probiotics Without Probiotics

Outcome Normalize bowel function Showed a faster normalization of stool

frequency and consistency
Methodology Randomized controlled trials Randomized controlled trials
Is it valid?
• Were the patients randomly assigned to treatment groups?
GUIDE QUESTIONS

• Was allocation concealed?

• Were baseline characteristics similar at the start or trial?
• Were patients and clinicians blinded to treatment?
• Were the outcome assessors blinded to treatment?
• Aside from the experimental intervention, were the groups
treated equally?
• Were all enrolled patients included in the conclusion of the
study?
Were the patients randomly assigned
to treatment groups? YES

In all 94 participants were randomized

as part of the ITT population, with 46
participants in the placebo group and
48 in the probiotic group.
(3 RESULTS – 3.1 Study Parameter, Page 438,
Column II, Paragraph 2 and
FIGURE 1 Participants’ enrollment, Page 439)
Was allocation concealed? YES
The probiotic and placebo capsules were
identical in appearance and taste.
(2 PARTICIPANTS AND METHODS –
2.3 Preparation of probiotic and placebo
capsule, Page 437, Column I, Paragraph 3
Were baseline characteristics similar
at the start or trial? YES

The baseline characteristics of the ITT population are presented

in Table 1, and were shown to be homogeneous in terms of age,
sex, body weight, BMI, heart rate, alcohol consumption and
smoking status (all P > 0.05).
(3 RESULTS – 3.2 Baseline characteristics of the participants, Page
438, Column II, Paragraph 3 and
TABLE 1 Baseline and clinical characteristics of the intention-to
treat population, Page 440)
Were patients and clinicians blinded
to treatment? YES
This was a prospective, randomized,
placebo-controlled, double-blind and
parallel-arm study.
(2 PARTICIPANTS AND METHODS –
2.2 Study design. Page 436, Column II,
Paragraph 4
Were the outcome assessors blinded
to treatment? YES
All study personnel were blinded to
the product. The randomization list
was computer-generated with a block
size of 4. The block size was not
disclosed to the investigators and
allocation was blinded to the
participants as well as the site staff.
(2 PARTICIPANTS AND METHODS –
2.2 Study design. Page 437, Column I,
Paragraph 1
Aside from the experimental intervention, were the
groups treated equally?

• Not mentioned
• Co-interventions also not mentioned
Were all enrolled patients included in
the conclusion of the study? YES
Altogether 88 participants completed the
study per-protocol (PP), with 41 in the placebo
group and 47 in the probiotic group. The ITT
population reported an overall mean
compliance of 98.3% in the placebo group and
99.0% in the probiotic group.
(3 RESULTS – 3.1 Study Parameter, Page 438,
Column II, Paragraph 2 and
FIGURE 1 Participants’ enrollment, Page 439)
What are the results?
What are the results?
What are the results?
What are the results?
Relative Risk (RR) = Rt/Rc
• Risk in Treatment (Rt) = not cured in treatment / N patients in
treatment
• Risk in Control (Rc) = not cured in control / N patients in control

Absolute Risk Reduction (ARR) = Rc-Rt

Relative Risk Reduction (RRR) = I-RR

Number Needed to treat (NNT) = I/RR

What are the results?
• Relative Risk (RR) = Rt/Rc
 Risk in treatment (Rt) = not cured in treatment / N patients in
treatment
1 / 48 = 0.02
 Risk in control (Rc) = not cured in control / N patients in control
5 / 46 = 0.11
Relative Risk (RR)
0.02 / 0.11 = 0.18 or 18%
What are the results?
• RR of 1. There is no difference Relative Risk (RR)
between the two groups thus,
the treatment had no effect
• RR < 1. The treatment
decreases the risk of the
outcome.
• RR > 1. The treatment
increases the risk of the
outcome.
0.02 / 0.11 = 0.18 or 18%
The administration of
Probiotics in patients with
functional constipation
decrease the risk to normalize
the stool frequency and
consistency.
What are the results?
Absolute Risk Reduction (ARR) = Rc-Rt Relative Risk Reduction (RRR) = 1-RR

0.11 - 0.02 = 0.09 or 9% 1-0.18 = 0.18 or 18%

The absolute benefit of giving There is 20% reduction of

Probiotics in patients with symptom in Probiotics in patients
functional constipation is 9% with functional constipation as
reduction of symptom. compared to none
What are the results?
• NNT = 1/ARR
1 / 0.09 = 11.11 or 11

We would need to treat 11 patients in order to

demonstrate normalization stool frequency and
consistency.
How precise was the estimate of
treatment effect?

• 95% CI
Acquiring the evidence

Appraising the evidence

Applying the evidence

Are the results applicable to my patients?
• Is my patient so different to those in the study that the
GUIDE QUESTIONS

results cannot apply?

• Are the medical, social and economic resources needed to
administer the treatment available in your setting?
• According to the study results, how much would my patient
truly benefit from the treatment?
• Are the treatment and consequences consistent with my
patient’s values and beliefs?
• Are the likely treatment benefits worth the potential harm
and costs?
Is my patient so different to those in the
study that the results cannot apply? YES
Biologic Issues Patient Study
Male and Female
Sex Female (Mostly female)
Co-morbidities None None
Age 33 years old 18 to 65 years old
Healthy adults with
Pathology Functional constipation symptoms of functional
constipation
Are the medical, social and economic resources
needed to administer the treatment available in
your setting? YES
YES
 Medical
 Social
 Economic Resources
According to the study results, how much would my patient
truly benefit from the treatment?

• The probiotic group showed a faster normalization of stool frequency

and consistency, with most participants achieving a normalized profile
after 1 week.
Are the treatment and consequences consistent
with my patient’s values and beliefs? YES

• Patients during consult, rely on their physician to do what is best to

resolve the symptoms (constipation)
Are the likely treatment benefits worth
the potential harm and costs? YES
• Based on relative risk

• Cost effectiveness Formula: NNT x price/unit x dose x duration

• 11.11 x P30.50 x 10days = P3,388.55
Recommendations
• Aligning the study inclusion with the study outcomes, because there
are significant variation in functional constipation outcomes.
• The limitations in the current study design may have ultimately
affected its ability to differentiate between groups. As it relates to
microbial profiling, the study did not assess colonic mucosal
microbiota, which may present differences from fecal microbiota in
functional constipation.
• Further studies, since the study employed Rome III criteria, Rome IV
criteria have since been released, which takes the view that functional
bowel disorders exist on a continuum instead of as discrete disorders.