Clinical Programme – Standards and Inspection

The Standards Section B

• B 1. General - programme size and organisation

• B 2. Clinical Unit Facilities

• B 3. Personnel

• B 4. Quality management

• B 5. Policies and Procedures

• B 6. Donor selection, evaluation and management

• B.7. Therapy administration

• B 8. Clinical research

• B 9. Data management

• B10. Records

Assessment of compliance

• Documentation

– Submitted

– Available on site

• Observation

• Interview

PlanGo through checklist and note what you need to see and who and what you need to ask

Documentation – Clinical programme

• Submitted before inspection– Organigramme of programme

– CVs, registration, evidence of

training, educational activity for

all senior medical staff

– Nursing summary (staffing,

training etc)

– Quality manual and SOP for SOP

– List of SOPs

– Patient and donor consent forms

– List of patients (Activity data)

– MED-A data for 10 consecutive

patients

• Documentation to see on site

– Patient notes

– Sample donor notes

– Selected SOPs (e.g. donor evaluation)

– Proformas for HDT

– Training records

– Audit reports

– Adverse Event (AE) reports

– Minutes of meetings

• Quality review meetings

• Patient management meetings

– etc

B 1. General - programme size and organisation

Definition of a programme

Programme size

B1.1 Definition of a Clinical Transplantation

Programme • i.e. what is considered as a “single

programme”

• particularly relevant to: – A combined adult and paediatric programme (on

same site or different sites)– Programmes with a second clinical site or “satellite”

units, e.g. local hospital doing a small number of autologous transplants.

• Rationale– two smaller programmes that are really working

separately should not join up just to meet activity targets for accreditation

B1.1 Definition of a Clinical Transplantation Programme

• an integrated medical team • housed in geographically contiguous or proximate space• single Programme Director• common

– protocols– quality management– training– data management

Programmes that include non-contiguous institutions in the same metropolitan area* must also demonstrate

• joint review of clinical results • evidence of regular interaction

* Defined for JACIE as “Geographically near enough to allow close and regular interaction”

B1. Evidence

• ?single Programme Director– documents (organigramme, minutes of meetings)

– interviews with staff (nurses, junior doctors)

• ? Common clinical protocols / training / QMP– documents

• SOPs• evidence of joint nursing training and competency assessment• Common patient database /data management• evidence of joint quality meetings

– Interview (nurses, junior doctors, quality manager)

• ? Regular interaction (non-contiguous units)– Documents (minutes of meetings etc)– Interview (especially staff at second site)

• B1.3 The Clinical Program shall abide by all applicable laws and regulations.

B 1.5 & 1.6 Programme size

• Minimum number of new allo or auto transplant patients in the preceding year (plus additional requirements for specific situations)

• Allo includes ID-sib, haplo, VUD, RIC-allo etc.

• The transplant unit can define the 12 month period but it must end within 12 months before the application

• The transplant unit must supply a complete list of patients for this 12 month period

B1.5 & 1.6 Programme Size

Programme Type

Total minimu

m require

d

Allominimu

m required

Autominimu

m require

d

Change re: 3rd edition

Allo OR Auto 10 or 5 10 OR 5 Auto minimum reduced from 10

Allo AND Auto

10 10 AND Nominimum

reqd

No total minimum and accredited allo unit considered to have met numeric

req for autos

Combined Paed & Adult programme

10 5 Adult and 5Paed for allo and same for auto

increased from 4

More than 1 clinical site

As above 5 per site increased from 4

B 2. Clinical Unit

what facility must have

safety requirements

B2. Clinical Unit Ward /OP

B2.1 There shall be a designated inpatient unit of adequate space, design, and location that minimizes airborne microbial contamination.

Guidance: “Inspectors will recognize that the unit facilities may vary between centres”

- recognition of an increasing use of ambulatory approaches to

transplantation,-the standard is not meant to imply that every

unit must have laminar airflow available-HEPA filtration with positive pressure is

recommended for high-riskpatients, but is not required for every unit.

B2. Clinical Unit Ward /OP

A designated area for outpatient care that reasonably protects the patient from transmission of infectious agents and can provide appropriate patient isolation, administration of intravenous fluids etc

Provisions for prompt evaluation and treatment by a transplant consultant/senior physician available on a 24-hour basis.

Nurses experienced in the care of transplant patients.

A nurse/patient ratio satisfactory to cover the severity of the patients’ clinical status.

Note - Inspector must make a judgement on these issues.

B2.3 Other required services

• A transfusion service providing 24-hour availability of CMV appropriate and irradiated blood products

• A pharmacy providing 24-hour availability of medications

• For allogeneic programmes, HLA testing laboratories accredited by the European Federation for Immunogenetics (EFI)

B2.Clinical Unit - Evidence

• Facilities - On site tour isolation facilities air handling (for high risk patients) - should be documentable

from a facilities management office. hand washing signage designated OP area - Can it be used for infusions?

• Nurse staffing Are there enough nurses available to cover the patients’ needs? Can nursing staff provide for >1nurse/patient if required? documentation / Interview senior nursing staff

• Safety issues– Documentation (SOPs, training logs) – Observation and Interview (safety training)

B 3. Personnel

B 3. Personnel

Team - including requirements for paediatric BMT

Programme director (PD) – qualifications, training, responsibilities

Other senior / consultant physicians - qualifications, training

Mid-level practitioners - training and competency

Nurses - training and competency, policies and SOPs

Consultants in other specialties – qualifications

Other staff (co-ordinator, dietitian etc)

Responsible for all administrative and clinical operations, including

selection of patients and donors, collection of cells, and processing of cells whether internal

or contracted services, quality management (can be delegated) Review of all AEs oversight of the medical care provided by the Programme

including medical care provided by the physicians on the transplant team.

verifying the knowledge and skills of the physicians of the transplant team.

Programme Director

PD - Evidence

• check he / she

– is responsible for administrative and medical operations of the Unit (interviews, minutes of meetings)

– Reviews the care of the attending physicians (interviews, minutes, outcomes audits, appraisals)

Other Staff - Evidence

Senior Physicians

• CV

• Training documents ; letter from PD etc

• CPD documentation

• interview

Mid level practitioners

• competency record

• interview

Other Staff - Evidence

• Nurses

•qualifications in haematology• in-service training log• personal CPD record• centrally kept competency record• SOPs for nursing procedures

• interview

• Other staff – seek confirmation of

•transplant co-ordinator•pharmacy staff•Dietetics•social support•physiotherapy staff•data management staff

B 5. Policies and Procedures (SOPs)

B5. Policies and Procedures

Evidence

Look at SOP for SOP

Look at selected SOPs – can request prior to visit

Look for evidence of document control - approval, date implementation, data review

Ask staff about SOPs – where and how to access

Observe if staff use the SOPs while carrying out a procedure

Ask to see how deviations are documented

B 6. Donor evaluation, selection and care

Evaluation procedures

Consent

B6. Donor EvaluationProcedures 1

procedures must address risk of disease

transmission to recipient and risk to donor from collection

There must be written criteria for donor evaluation and selection.

The use of a donor not meeting the criteria must require documentation of the rationale for his/he selection by the transplant physician and the informed consent of the donor and the recipient.

For allogeneic donors, A transplant physician must document in the recipient’s medical record the prospective donor’s suitability before the recipient’s high-dose therapy is initiated.

* unless otherwise specified applies to allogeneic and autologous donors

B6. Donor Evaluation Procedures 2

Procedures must be in place to ensure both

confidentiality of donor and patient health information.

Any abnormal findings must be reported to the prospective donor with documentation in the donor record of recommendations made for follow- up care.

Issues of donor health that pertain to the safety of collection procedure must be communicated in writing to the collection facility staff.

B6. Donor Evaluation Procedures 3

Prospective donors must be evaluated by medical history,

physical examination and laboratory testing.

The medical history must include at least the following

Vaccination history

Travel history.

Blood transfusion history

Questions to identify persons at high risk for significant transmissible infections.

B6. Donor EvaluationProcedures – 4 IDM

B6.6.1 Within 30 days* prior to (each) collection, each donor must be tested for evidence of infection by the following communicable disease agents:

Human immunodeficiency virus, type 1Human immunodeficiency virus, type 2Hepatitis B virusHepatitis C virusHuman T-lymphotropic virus, type I**Human T-lymphotropic virus, type IITreponema pallidum (syphilis)Cytomegalovirus) (unless previously documented to be positive)

*HTLV will only be required if there are specific risk factors

Allogeneic Donors

HLA-A, B, DR typing by an EFI-accredited laboratory.

ABO group and Rh type and appropriate red cell compatibility with the recipient.

Pregnancy assessment for all female donors of childbearing potential *

* In 3rd edition assessment must be within 7 days of stanting conditioning of allgeneic recipient or of stanting mobilisation if autologous donor

B6. Donor Evaluation Procedures Other tests

Informed consent from the donor must be obtained and documented by a licensed physician or other

health care provider familiar with the collection procedure

(for allogeneic donors, before the high dose therapy of the recipient is initiated.)

The procedure must be explained in terms the donor

can understand, and must include information about the significant risks and benefits of the procedure and tests performed to protect the health of the donor and recipient and the rights of the donor to review the results of such tests.

(Does not specifically have to be written info but probably should be)

B6. Donor Consents

B 7.Therapy administration

High dose chemotherapy

Administration of HPC

B7.000 Therapy Administration

B7.1 There must be a written policy to ensure that the preparative regimen is administered safely.*

B7.1.1.1 The treatment orders must include the patient height and weight, specific dates, daily doses (if appropriate) and route of each agent. Pre-printed orders should be used for protocols and standardised regimens.

B7.1.1.3 The pharmacist preparing the chemotherapy must verify the doses against the protocol or standardised regimen listed on the orders.

B7.1.1.4 Prior to administration of chemotherapy, two persons qualified to administer chemotherapy must verify the drug and dose in the bag or pill against the orders and the protocol, and the identity of the patient to receive the chemotherapy.

Similar principles for radiotherapy

B7.000 Therapy Administration

B7.2 There shall be a policy to ensure safe administration of cellular therapy products.

B7.2.1 Two qualified persons must verify the identity of the recipient and the product prior to the infusion of the product.

B7.2.2 There must be documentation in the patient’s medical record of the unit identifier for all infused products.

Therapy Administration Evidence

• Therapy administration

– Ask to see protocols in the Unit and Pharmacy

– Review patient charts to confirm treatment given

– Interview pharmacist and nurses about normal practice

– Ask nursing staff about chemotherapy training

– May watch treatment being given to check practice against SOP

B 8. Clinical Research

requirements

Formal review of investigational treatment protocols Documentation for all research protocols Informed consent

arrangements for financial disclosure

evidence Are investigational protocols undertaken? If yes

see protocolsee ethics Committee and R&D approvalsee patient info sheetsSee evidence of patient consent

B8. Clinical Research

B 9. Data Management

B9. Data Management

• The Programme must– keep complete and accurate patient records.– collect all the data contained in the Minimum

Essential Data Forms of the EBMT.– use its data to periodically audit patient outcomes.

• Evidence– on site audit of notes/ MED A data– audit reports, annual reports etc

• Note– Outcomes are not a standard– Reporting to the EBMT/IBMTR is not a standard

B 10. Clinical Unit Records

B10. Records

B10.5 Records In Case Of Divided Responsibility

B10.5.1 If two or more facilities participate in the collection, processing or transplantation of the product, the records of each facility must show plainly the extent of its responsibility.

B10..5.2 The Programme must furnish to other facilities involved in the collection or processing of the product, transplant outcome data in so far as they concern the safety, purity and potency of the product involved.i.e. Engraftment data, AEs

Clinical Programmes – Most Common and Important Deficiencies

•B6 - Donors

•B6.3.2 - IDMs not tested within 30 days of collection

•B9 - Data management

•B4.10.4 - Corrective actions

•B2.6 - Outpatient area

• - Discharge

Common problems with Clinical Programme

• Different units not functioning as a single programme - (lack of common training, common SOPs, close and regular interaction)

• Training of medical staff not documented

• Quality management problems

– Adverse event reporting not adequate (e.g. adverse events not reviewed by Programme director

– No regular audits or infrequent audits

Common problems with Clinical Programme

SOPS• SOPs

– references not included– examples of forms and labels not

appended to SOPs– SOPs not reviewed annually

• Inadequate document control

• deviations from SOPs not documented

Common ProblemsPatient / Donor issues

No record of verification of patient’s diagnosis

Not clear if donor is always informed of abnormal results and if arrangements are made for follow-up

No formally documented criteria for defining suitable donor

Not clear how the decision is made to use a donor not meeting the programme’s selection criteria

Pregnancy not always assessed in female donors of childbearing age

B6.000 Donors - Problems

• Lack of written donor information

e.g. collection procedures and risks of G-CSF, central lines

• Missing/inconsistent donor info e.g. travel, transfusion, immunisation histories

• Lack of clear selection criteria

• No clear ‘final authorisation’

• Not relaying donor info to collection facility

• No record in patient record of donor suitability e.g. HLA, CMV, ABO

SOLUTIONS• Clear,

comprehensive

and unambiguous

policies and

procedures

• Checklists

• Final approval

documents

Testing for IDMs

• B6.1 states that “there shall be donor evaluation procedures to protect the recipient from the risk of disease transmission from the donor”

• B6.6 “Within 30 d prior to collection all HPC donors shall be tested for evidence of clinically relevant infection – HIV 1/2, HBV, HCV, HTLV 1/2*, syphilis

• Deficiencies – medical history doesn’t include the correct questions

- specific tests e.g. syphilis omitted - not repeated if SCT delayed

Data Management

• B9.1 describes the requirement to collect all TED/MED-A data

• At a minimum – patient outcomes, donor screening and testing and recipient 100d mortality

• Deficits – incomplete or incorrect forms, lack of engraftment data

- clinical status at SCT not well recorded

- lack of chemo prescription, date of administration not recorded