Guidelines in Chemotherapy

Djumhana Atmakusuma

Dharmais Cancer Hospital

Guidelines

Evidence base medicine:

- level of evidence

- grade of recommendation

Consensus Evidence base medicine

modified (plus local

considerations +

experiences ?)

Standard

operating

procedures

(SOP)

Must be done (mandatory)

Protocols

Guidelines

Consensus

Standard

operating

procedures

(SOP)

Protocols

Clinical Pathway

Guidelines

• A medical guideline (also called a clinical guideline, clinical protocol or clinical practice guideline) is a document with the aim of guiding decisions and criteria regarding diagnosis, management, and treatment in specific areas of healthcare. Such documents have been in use for thousands of years during the entire history of medicine. However, in contrast to previous approaches, which were often based on tradition or authority, modern medical guidelines are based on an examination of current evidence within the paradigm of evidence-based medicine. They usually include summarized consensus statements, but unlike the latter, they also address practical issues.

• Modern clinical guidelines briefly identify, summarize and evaluate the best evidence and most current data about prevention, diagnosis, prognosis, therapy including dosage of medications, risk/benefit and cost-effectiveness. Then they define the most important questions related to clinical practice and identify all possible decision options and their outcomes. Some guidelines contain decision or computation algorithms to be followed. Thus, they integrate the identified decision points and respective courses of action to the clinical judgment and experience of practitioners. Many guidelines place the treatment alternatives into classes to help providers in deciding which

• Additional objectives of clinical guidelines are to standardize medical care, to raise quality of care, to reduce several kinds of risk (to the patient, to the healthcare provider, to medical insurers and health plans) and to achieve the best balance between cost and medical parameters such as effectiveness, specificity, sensitivity, resolutiveness, etc. It has been demonstrated repeatedly that the use of guidelines by healthcare providers such as hospitals is an effective way of achieving the objectives listed above, although they are not the only ones.

GRADE OF CLARITY OF

METHODOLOGIC IMPLICATIONS

RECOMMENDATION RISK/BENEFIT

STRENGTH OF

SUPPORTING EVIDENCE

A.Randomized controlled trials

(RCTs) without important limitations

B. RCTs with important limitations

C+: No RTCs

C: Observational studies

1. Risk / Benefit:

CLEAR

2. Risk / Benefit:

UNCLEAR

• 1A : 1. Risk/benefit: Clear

A. Randomized controlled trials (RCTs) without important

limitations

Implications: Strong recommendation; can apply to most

patients, in most circumstances,

without reservation

• 1B: 1. Risk/benefit: clear

B. RCTs with important limitations (inconsistent results,

methodologic flaws*)

Implications: Strong recommendation; likely to apply to

most patients

• 1C+ : 1. Risk/benefit clear

C+. No RCTs, but RCT results can be unequivocally

extrapolated; or, overwhelming evidence from

observational studies

Implications: Strong recommendation; can apply to most

patients, in mostcircumstances

• 1C: 1. Risk/benefit: clear

C. Observational studies

Implications: Intermediate-strength recommendation; may

change when stronger evidence available

• 2A : 2. Risk/benefit: Unclear

A. RCTs without important limitations

Implic. : Intermediate-strength recommendation; best

action may differ, depending on circumstances or

patients’ or societal values

• 2B: 2. Risk/benefit: Unclear

B. RCTs with important limitations (inconsistent results

methodologic flaws)

Implic. : Weak recommendation; alternative approaches,

likely to be better for some patients under

some circumstances

• 2C: 2. Risk/benefit: Unclear

C. Observational studies

Implic. : Very weak recommendation; other alternatives

may be equally reasonable

* Such situations include RCTs with lack of blinding, and

subjective outcomes, in which the risk of bias in measurement

of outcomes is high; and RCTs with large loss to follow-up.

Consensus

• Consensus has two common meanings.

One is a general agreement among the

members of a given group or community,

each of which exercises some discretion in

decision making and follow-up action. The

other is as a theory and practice of getting

such agreements (for information on the

practice of achieving formal consensus,

see consensus decision-making).

• Achieving consensus requires serious treatment

of every group member's considered opinion.

Once a decision is made it is important to trust in

members' discretion in follow-up action. In the

ideal case, those who wish to take up some

action want to hear those who oppose it,

because they count on the fact that the ensuing

debate will improve the consensus. In theory,

action without resolution of considered

opposition will be rare and done with atte

Standard Operating Procedure

(SOP)

• The terms standard operating

procedure and standing operating

procedure, both abbreviated as SOP, are

used in a variety of different contexts:

healthcare, education, industry, military,

etc

• A standard operating procedure is a set of

instructions having the force of a directive,

covering those features of operations that lend

themselves to a definite or standardized

procedure without loss of effectiveness.

Standard Operating Policies and Procedures

can be effective catalysts to drive performance

improvement and improving organizational

results. [1] Every good quality system is based

on its standard operating procedures (SOPs).

• Protocols ??

Clinical Pathway

CLINICAL PATHWAYS

Multidisciplinary plans (or blue print

for a plan of care) of best clinical

practice for specified groups of

patients with particular diagnosis

that aid in the coordination &

delivery of high quality of care.

Dr Amrizal Muhammad Nur

• Clinical pathway:

- Management & clinical audit tools

- Began with admission & ended with

discharge (“Predictable”)

- Interdiscipinary in focus

- Merging the medical & nursing plans

of care with other disciplines (e.g;

physiotherapy, nutrition, mental health

etc)

Clinical Pathway

Dr Amrizal Muhammad Nur

Episode Model with Stages and Clinical Activities

Problem Diagnosis Therapy Follow Up

Clinical Events

1

Start End

Activities Activities Activities Activities Activities

DBC

2 3 4 5

Intake Diagnosis Pre Therapy Therapy Follow upSTAGES

1

Dr Amrizal Muhammad Nur

Management of Acute Leukemia

Initial Phase

- Diagnosis

MIC (cytology,

flowcytometry,

cytogentics)

- Treatment of

complications

Induction

Therapy

- Pre-induction

tests: focal

infections,organ/

system

abnormalities

- Induction

chemotherapy:

- AML: D3C7

- ALL: LALA 87

Consolidation

Therapy

Treatment of

complications of

chemotherapy

- Consolidation

chemotherapy:

- AML: D3C7

- ALL: LALA 87

Maintenance

Therapy

Hemopoietic

Stem Cell /

Bone Marrow

Transplant-

ation

Follow-

up

Treatment of

complications of

chemotherapy

(1 day–1 week)

(> 1 month)

(> 1 month)

(> 2 years)

(weeks,

months, years)

(> 1,2,5 yrs)

Relaps:

Treatment

How to develop Consensus & Clinical

Pathway in Dharmais Cancer Hospital

Cancer Working Groups

13 cancer working groups (from 28 medical staff group)

• Gynelogical cancer (cervix, ovarium, korpus uteri)

• Breast cancer

• Nasopharyngeal cancer

• Blood cancers

• Lung cancer

• GIT & hepatic cancer

• Urogenital cancer

• Head & neck cancer

• Musculosceletal cancer

• Skin cancer

• Brain cancer

• Pediatric cance

• Ophthalmologic cancer

Guidelines Consensus

• Revision/Development: August 2005-August 2007 (2 yrs) : - 13 Tim Cancer Working Groups

- 54 cancers 82 consensus

• Format: - NCCN algorithm & manuscript

- Algorithm NCCN = clinical pathway

diagnosis, treatment, follow-up,

complication, co-morbidities

• Problems: difficulties in achieving consensus among member of the team in terms of D/, Th/ and follow up ( many references: NCCN, ICN, ASCO, ECCO, ESMO, cancer working groups)

Management of Acute Leukemia

Guideline of the Management of Acute Leukemia:

NCCN, NCI (USA)–Working Group (Europe, others)

evidence base medicine (EBM):

grade of recommendation - level of evidence

National Consensus

on the Management of Acute Leukemia

Hospital Consensus:

Best Clinical Practice

Essential Care

Package = PPE

Self Experience

Clinical Pathway of “ Best Clinical Practice”

and “Essential Care Package (PPE)”

Hospital Consensus: Best Clinical Practice

Hospital Consensus

Best Clinical Practice

+ Nursing SOP +

Nutrition SOP, others

Revision of Essential

Care Package = PPE

Clinical Pathway

of “Best clinical

practice”

Clinical Pathway

of PPE

Clinical Pathway of Acute Myeloblastic

Leukemia (Outpatient or Inpatient Settings)

• CP 1: Diagnosis of Acute Myeloblastic Leukemia

• CP 2: Initial Treatment of Complications

of Acute Myeloblastic Leukemia

• CP 3: Pre-induction Tests

• CP 4: Induction Chemotherapy (CP 4 a, CP 4 b, CP 4 c, etc)

• CP 5: Consolidation Chemotherapy (CP 5 a, CP 5 b, CP 5 c, etc)

• CP 6: Maintenance Chemotherapy (CP 6 a, CP 6 b, CP 6 c, etc)

• CP 7: Treatment of Complications of the Treatment

• CP 8: Follow up of Acute Myelogenous Leukemia (CP 8)

• CP 9: Bone Marrow Transplantation (CP 9 a Autologous BMT, CP 9 b Allogeneic BMT)

• CP 10: Peripheral Blood Stem Cell Transplantation (CP 10 a Autologous PBSCT, CP 10 b Allogeneic PBSCT)

Intervention Visit/Day 1 Visit/Day 2 Visit/Day 3 Visit/Day 4 Visit/Day 5

Assessment Admission :

Demographic data

& other information

Consultation

& Nursing

Care

- Hematologists-

Med. Oncologists

- Clin. Pathologist

Clin. Pathologists

information the result to

HOM (Rp ?)

Diagnostic /

procedures

- Bone marrow

aspiration/ biopsy

- Peripheral blood

aspiration (Rp ?)

Laboratory

tests

- Cytology,Cytoche

mistry, flowcytome

try, Cytogenetics,

DNA analysis

- CBC,blood smear,

hemostasis (Rp

- Results of Lab tests:

cytology,

cytochemistry, CBC,

blood smear,

hemostasis

Result of Lab tests:

Flow cytometry

- Results of Lab tests:

Histology of BMB

plus imprint cytology

- Results of Lab tests:

Cytogenetics & DNA

analysis

Medications /

Nutrition

-Paracetamol

-Free diet *Rp ?)

Information /

Education

- Information (oral

/ written)

- Informed consent

Results cytology/che-

mistry & flowcytome-

try & th/ are informed

to a patient

- Final result is inform

ed to a patient

- Final treatment is

inform- ed to a patient

Outcome - A patient accepts

BMA/BMB

- No complications

- Diagnosis of AML

(cyto-logy/-chemistry)

are finished

- Diagnosis of AML

(immunoctochemistry

/ flowcytometry) is

finished

- Diagnosis of AML

(histology BMB &

imprint cytology) are

finished

- Diagnosis of AML

(cytogenetics & DNA

analysis are finished

Varians

CP 1 (Best Clinical Practice): Acute Myeloblastic Leukemia: - ICD 10: C 95.0

Diagnostic Procedures of AM: - ICD 9-CM:

Persons in charge: Doctor I: Doctor II: Nurse:

Intervention Visit/Day 1 Visit/Day 2 Visit/Day 3 Visit/Day 4 Visit/Day 5

Assessment Admission

Demographic data

& other information

- Admission - Admission - Admission - Admission

Consultation - Hematologist-

Medical Oncologist

- Dentist

- ENT specialist

- Cardiologist - Dentist (result of

panoramic x-ray)

- HMO

Diagnostic /

procedures

- X – ray: Chest ,

teeth panoramic

-EC

-Echocardiography

- Teeth extraction - Teeth extraction

Laboratory

tests

-CBC, LFT, kidney

function, blood

sugar, uric acid

- Cultures (throat,

urine, stool, blood)

- Hepatitis B,C, HIV

- Results of Lab tests:

all laboratory tests,

except cultures

- Results of cultures

are finished

Medications /

Nutrition

- Free diet - Treatment of focal

infection

- Treatment of focal

infection

- Treatment of focal

infection

Information /

Education

- Information (oral

/ written)

- Informed consent

HMO: information:

- results of diagnosis

& treatment

- induction therapy

Outcome - A patient accepts

all activities

- No complications

No abnormalities - All abnormalities (+

infections) disappear

- A patient is ready for

induction therapy

Varians

CP 3 (Best Clinical Practice): Acute Myeloblastic Leukemia: - ICD 10: C 95.0

Pre – induction tests: - ICD 9-CM:

Persons in charge: Doctor I: Doctor II: Nurse:

Intervention Day 1 Day 2 Day 3 Day 4 Day 5

Assessment Admission

Demographic data

& other information

Nurses assessment Nurses assessment Nurses assessment Nurses assessment

Consultation - Hematologist-

Medical Oncologist

Visit HMO

Visit doctor in charge

Visit HMO

Visit doctor in charge

Visit HMO

Visit doctor in charge

Visit HMO

Visit doctor in charge

Diagnostic /

procedures

ECG, if necessary

Chest X-ray if

necessary

Laboratory

tests

-CBC, LFT, kidney

function, blood

sugar, uric acid

- Cultures (weekly)

CBC CBC CBC, LFT,KF,BS CBC

Medications /

Nutrition

-Oral & parentheral

-Pre medications

-D1 Chemotherapy

- See protocols

-Pre medications

-Day 2. Chemotherapy

-Pre medications

-Day 3 Chemotherapy

-Pre medications

- Day 4 Chemotherapy

-Pre medications

-Day 5 Cehmotherapy

Information /

Education

- Information (oral

/ written)

- Informed consent

- Daily information:

a today program

response & adverse

reactions

- Daily information:

a today program

response & adverse

reactions

- Daily information:

a today program

response & adverse

reactions

- Daily information:

a today program

response & adverse

reactions

Outcome - A patient is ready

and suitable for the

induction

cheotherapy

No adverse events of

chemotherapy

No adverse evets of

chemotherapy

No adverse evets of

chemotherapy

- Daily information:

a today program

response & adverse

reactions

Varians

CP 4.a. (Best Clinical Practice): Acute Myeloblastic Leukemia: ICD 10:C 95.0

Induction chemotherapy “D3C7 regimen”: - ICD 9-CM: 39.35

Persons in charge: Doctor I: Doctor II: Nurse:

Intervention Day 6 Day 7 Week 2 Week 3 Week 4

Assessment Nurses assessment Nurses assessment Nurses assessment Nurses assessment Nurses assessment

Consultation Visit HMO

Visit doctor in

charge

Visit HMO

Visit doctor in charge

Visit HMO

Visit doctor in charge

Visit HMO

Visit doctor in charge

Visit HMO

Visit doctor in charge

Diagnostic /

procedures

ECG, if necessary

Chest x ray if neces

ECG weekly

Chest x ray if necess

ECG weekly

Chest x ray if necess

ECG weekly

Chest x ray if necess

Bone Marrow Aspirat.

Laboratory

tests

-CBC CBC, LFT, KF,BS,

cultures

CBC CBC, LFT,KF,BS CBC , bone marrow

cytology-chemistry,

flow cytometry,DNA

Medications /

Nutrition

-Oral & parentheral

-Pre medications

-D6 Chemotherapy

- See protocols

-Pre medications

-Day 7 Chemotherapy

- Antiemetics drugs

- Supportive drugs

- Blood transfusions

- Antiemetics drugs

- Supportive drugs

- Blood transfusions

- Antiemetics drugs

- Supportive drugs

- Blood transfusions

Information /

Education

- Information (oral

/ written)

- Informed consent

- Daily information:

a today program

response & adverse

reactions

- Daily information:

a today program

response & adverse

reactions

- Daily information:

a today program

response & adverse

reactions

- Daily information:

a today program

response & adverse

reactions

Outcome - A patient is ready

and suitable for the

induction

cheotherapy

No adverse events of

chemotherapy

No adverse evets of

chemotherapy

No adverse evets of

chemotherapy

- Daily information:

a today program

response & adverse

reactions

Varians

CP 4.a. (Best Clinical Practice): Acute Myeloblastic Leukemia: ICD 10:C 95.0

Induction chemotherapy “ D3C7 regimen”: - ICD 9-CM: 39.35

Persons in charge: Doctor I: Doctor II: Nurse:

Conclusion

Guidelines

Evidence base medicine:

- level of evidence

- grade of recommendation

Consensus Evidence base medicine

modified (plus local

considerations +

experiences ?)

Standard

operating

procedures

(SOP)

Must be done (mandatory)

Protocols

Guidelines

Consensus

Standard

operating

procedures

(SOP)

Protocols

Clinical Pathway

• Indonesia ?? Guidelines ???