![](media/image1.png)

## **SNOMED International**

**A Division of College of American Pathologists**

**Written Comments to**

**Food and Drug Administration**

**Safety Reporting Requirements**

**for Human**

**Drug and Biological Products**

**April 14, 2003**

College of American Pathologists

325 Waukegan Road

Northfield, Illinois 60093

\(847\) 832-7000

\(847\) 832-8000 - Fax

\(800\) 323-4040

www.SNOMED.org

# **ORGANIZATION BACKGROUND**

The CAP is a not-for-profit medical society serving nearly 16,000
physician members and the laboratory community throughout the world. The
CAP is an advocate for high quality and cost-effective patient care. The
College has approximately 40 years of experience in the development and
ongoing maintenance of controlled clinical terminology and specifically
SNOMED^®^, the Systematized Nomenclature of Medicine. It's experience in
the development and ongoing maintenance of controlled clinical
terminology extends well beyond just the interests of pathologists.
SNOMED International and the CAP appreciate the opportunity to comment
on the proposed rule.

.

**THE COLLECTION OF INFORMATION FOR DRUG SAFETY:**

**RECOMMENDATION**

The Food and Drug Administration is proposing to amend its pre- and
postmarketing safety reporting regulations for human drug and biological
products. As reported in the Federal Register / Vol.68, No. 50, "the
intended effect of these changes is to further worldwide consistency in
the collection of safety reports and submission of safety reports,
increase the quality of safety reports, expedite FDA's review of
critical safety information, and enable the agency to protect and
promote public health." The proposed changes are viewed as an "important
step toward global harmonization of safety reporting" and a way to
"harmonize the reporting requirements of U.S. Federal
agencies...continuing to work together to address the best ways to
streamline information sharing and harmonization."

[We propose that the agency reconsider its approach by differentiating
the requirements for the collection of safety data from the requirements
for the aggregation and use of the data for specific analytical and
reporting purposes.]{.underline}

[More specifically, we propose that the agency consider SNOMED
CT]{.underline}^®^ [as a more appropriate terminology for the collection
of safety data if harmonization and administrative simplification is
indeed a goal.]{.underline}

**THE RATIONALE**

Patient safety issues will vary over time and across clinical
investigators, sponsors and research organizations. The agency's own
proposed rule spans a range of safety issues, sources and uses of safety
data as well as urgency of reporting:

-   Minimum data set and full data set for an individual case safety
    report prepared by manufacturer or applicant;

-   Active query with the initial report of a suspected adverse drug
    reaction or medication error by a health care professional that
    includes the collection of patient history, physical exam,
    diagnostic results, and supportive lab tests;

-   Supporting documentation for a report of a death or hospitalization
    (e.g., autopsy report, hospital discharge summary);

-   Spontaneous reports from an individual health care professional or
    consumer;

-   Company core data sheet prepared by applicants for a drug substance
    which contains material related to indications, dosing, pharmacology
    and other information in addition to safety information;

-   Reports of actual or potential medication errors;

-   U.S. Drug labeling for an approved drug or licensed biological.

Therefore, we believe safety reporting and health care delivery requires
a terminology standard that is a broad integrated whole, not a
collection of domain-specific or use specific terminology fragments. The
terminology infrastructure must have breadth, scope and sustainable
maintenance processes to ensure that it not only meets the needs of
today, but those of tomorrow. Finally, to foster efficiency and
expedited reporting, the many different uses (e.g., safety
documentation, research, public health, health care delivery and
decision support) in addition to the FDA's safety reporting initiatives,
should rely on the same detailed clinical information that is gathered
at the point of care and aggregated, analyzed and ultimately reused for
different purposes.

To meet these requirements, safety reporting and healthcare delivery
needs a clinical terminology standard that:

-   Creates internal consistency within and between the electronic
    patient record, study case report forms, and FDA safety reports;

-   Facilitates information sharing with government agencies, sponsors
    and contractors of clinical research and investigators, in addition
    to caregivers from various clinical/functional groups, practicing
    across the continuum of care, with different computer platforms;

-   Provide for consistent and complete retrieval required for public
    health and safety reporting as well as population based studies at a
    very detailed level using data collected by different sources and
    disparate methods;

-   Enable aggregation and analysis at levels of abstractness that may
    differ from when the data was collected;

-   Meet the essential elements of good terminology design as recognized
    by the medical informatics community and U.S. standards
    organizations.

Active queries and other database analyses to rule out the causal
relationship between a product and an adverse event requires collecting,
aggregating and correlating data about the trigger event, and medical
and surgical interventions used to treat the event. This means
integrating data points. Emergency room data may have to be linked to
laboratory data for a definitive diagnosis and integrated with
radiologic findings and even prescribing information in a timely manner.
Such efforts would be greatly facilitated by a standard clinical
terminology that is used at the point of care.

Evidence indicates that SNOMED CT fulfills these basic requirements for
the collection of safety data more effectively than MedDRA at this time.

Testimony to the Institute of Medicine (IOM) Committee on Patient Safety
Data Standards earlier this year from Blackford Middleton and others
suggested that the committee establish acceptable standard controlled
vocabulary and codes for a minimum data set, and recognized SNOMED CT
within an HL7 RIM message as a means to achieve the level of "semantic
interoperability" (i.e., interoperability based on meaning) that is so
critical to patient safety and health care delivery. We concur and
further recommend that SNOMED CT be the central ingredient in any
patient safety infrastructure.

In March of this year, the National Committee on Vital and Health
Statistics (NCVHS) Subcommittee on Data Standards for the Patient
Medical Record received a report from its consultant evaluating 38
clinical terminologies against specific criteria. Only ten terminologies
were perceived to meet the essential criteria, SNOMED CT being the most
comprehensive and rated the highest.

The National Library of Medicine and the College of American
Pathologists are in the final stages of executing a contract for the
distribution of SNOMED CT through the Library's UMLS Metathesaurus. This
would make SNOMED CT widely available to the research and patient care
community. Combined with the recognition of the SNOMED CT Structure as
an ANSI standard and the current evaluation of SNOMED CT by the
Consolidated Healthcare Informatics as part of the e-gov initiative,
SNOMED CT is best positioned as a, if not the, clinical terminology
standard for the U.S. The same cannot be said for MedDRA.

As part of its long-term strategy, the CAP recognizes the importance of
consistency internationally to enable data transfer and accurate
communication across the globe. To that end, the CAP has been working
with the National Health Service in the United Kingdom, the developers
of Clinical Terms V.3 formerly known as the READ codes, to further
deploy SNOMED's value beyond national borders and maximize utilization
of resources available to develop a truly comprehensive and
internationally accepted clinical terminology. The U.K. Information
Strategy for Health states that "Subject to successful testing for
implementability, after 1 April 2003\... Electronic patient records and
Electronic Health Records should use the NHS preferred clinical
terminology, SNOMED® Clinical Terms."[^1]

SNOMED CT users currently exist in 28 countries. A number of the
national governments of these countries are evaluating SNOMED CT as
their clinical terminology standard as they modernize their respective
health care infrastructures.

In addition, third party evaluations of earlier editions of SNOMED have
shown that SNOMED was superior to other terminologies and classification
schemes specifically for use in adverse event reporting. In a paper by
Liu et al[^2], an object-oriented representation of contraindications
was proposed that would allow computerized checking of drug prescription
safety. It distinguished four types of contraindications: pathological
state, physiological state, findings of investigation procedures and
diagnostic or therapeutic procedures. The vocabulary usable for
expressing the contraindications appropriate for automated prescription
checking was also investigated. SNOMED was shown to give "coverage of
the largest number of categories and thus appears to fit best to the
needs of a database on contraindications."

The experience with the UK and other countries will enable shared
patient safety initiatives on a global basis.

**ABOUT SNOMED CT**

SNOMED CT, comprehensive clinical terminology used to code, retrieve and
analyze clinical data is "best of breed." SNOMED CT content and
structure are well positioned to fulfill the role of collecting safety
data. The breath, scope and expressivity of SNOMED CT are unparalleled.
Its quality has been consistently rated #1 by independent third parties.
[^3] [^4]

The scope of SNOMED CT encompasses the entire medical record. The
terminology can precisely represent clinical information across the
scope of health care. The January 2003 version of SNOMED CT contains
more than 333,000 medical concepts, over 900,000 descriptions or
synonyms related to these concepts, and approximately 1,300,000 computer
readable hierarchical and semantic relationships between concepts. (See
Appendix 1&2) Represented are symptoms (e.g., rash and erythema);
findings and diagnoses (such as ventricular fibrillation, liver
necrosis, S3 Gallop, anthrax septicemia and widening of mediastinum);
living organisms; medications (at the clinical and proprietary drug
level with dosage forms, strengths, units, routes of administration);
blood and blood components; chemical substances (including vaccines,
toxins, and contrast agents); medical devices; laboratory tests and test
results (e.g., serum potassium level); procedures (e.g., sigmoidoscopy);
anatomic structures and standard assessment tools (such as Glasgow Coma
Scale, Bethesda Codes).

The ability to record detailed information on adverse drug reaction
relies upon existence of terminology content in two areas. Drugs
themselves, and the disorders, signs and symptoms that may be the result
of an adverse reaction to the drug. SNOMED CT is very rich in both of
these areas as exemplified by the example of U.S. drug labeling vs.
SNOMED content for adverse effects associated with the drug Moricizine.
(See Appendix 3)

Many of the common medical concepts are used across clinical domains,
and, at varying levels of specificity:

-   Symptoms, signs, disorders may be documented by nurses, physicians,
    allied health professionals and veterinarians.

-   A laboratory test performed may be documented in the lab using a
    test name that indicates analyte, method and scale, (i.e. LOINC or
    local code) whereas the order is written at the more general level
    (e.g., serology rickettsial antibody test).

The SNOMED CT structure links equivalent expressions to the appropriate
medical concept and aggregates concepts across multiple hierarchies. It
defines each concept semantically. (See Appendix 4) Physicians, nurses,
pharmacists and other clinicians can express concepts at the level of
detail appropriate to them. It provides a single integrated terminology
for the many different types of concepts that must be linked to each
other for safety reporting and care delivery:

-   Allergies to drugs

-   Procedures to devices

-   Diseases to contraindications.

An example related to cytovene is presented in Appendix 5.

The computer-readable format enables the clinical concepts reported by
one person in one software system to be interpreted and linked to terms
with the same meaning in another system, providing enhanced
compatibility across software applications. And, SNOMED makes it
possible for patient safety reports other than drug safety reports
(e.g., adverse events that occur during surgery) to use the same
underlying infrastructure. It streamlines record keeping by facilitating
better communication and reuse of coded information. Thus, by supporting
the day-to-day work of clinicians, SNOMED CT addresses, at the same
time, the special needs of investigators, such as safety reporting. For
example:

-   Its content is used to meet some of the most pressing patient safety
    needs related to electronic drug and laboratory order entry.
    University of Nebraska for example, initiated an electronic order
    entry system using SNOMED CT for its problem lists.

-   Its breadth facilitates therapeutic decision support as is
    demonstrated by use of SNOMED CT within TheraDoc's expert system
    inference engine used at University of Utah Health Sciences Center.
    The new proprietary US drug extension of SNOMED CT released earlier
    this year brought into a single terminology framework codes for
    indications, contraindications, allergies, side effects, virtual
    drug and proprietary product information.

-   SNOMED CT includes codes, hierarchies and semantic definitions for
    the National Quality Forum's (NQF's) never events, to support
    patient safety initiatives.

-   All medical concepts needed to code and analyze autopsy reports,
    another important patient safety measure, are included and have been
    successfully used to establish a web-based autopsy database at Duke
    University.

-   Other users like Micromedix are tagging content using SNOMED CT to
    facilitate just-in-time access to knowledge bases that can prevent
    errors from occurring.

-   The CAP has been working with the Centers for Disease Control and
    the American College of Surgeons Commission on Cancer. As of January
    2004, the Commission requires that data elements contained in CAP's
    cancer checklists be reported for each site and specimen as part of
    its accreditation program. These checklists will be available as
    SNOMED CT encoded templates to reduce errors of omission and to
    facilitate accurate electronic reporting.

-   Life sciences researchers are using SNOMED CT for indexing and
    mining information from databases. Genelogic, a provider of
    genomics-based information products and services, stores and
    retrieves tissue samples that match the highly specific criteria of
    researchers.

The SNOMED CT semantic infrastructure also facilitates the complete and
consistent retrieval of data for clinical research, postmarketing safety
reporting, outcome analysis and other public health analyses, allowing
aggregation at varying levels of specificity and by a wide variety of
defining characteristics (e.g., etiology, drug, morphology, etc.).

The design of SNOMED CT has been driven by the expressed needs of the
market place for features that improve their ability to develop useful
applications. In response to these needs, the design adds unique numeric
identifiers, includes links to legacy codes, supports a sustainable
migration and maintenance strategy, permits adaptability for national
purposes, and fosters alignment with other standards such as HL7, XML,
and DICOM.

As an American National Standards Institute (ANSI) approved standards
developer, the College of American Pathologists has committed to a
review process that incorporates ANSI's minimum due process
requirements. The SNOMED CT structure has been balloted as an ANSI
standard and at the close of the balloting process, CAP reported that
74% of the canvass list voted. Of those responding to the initial and
recirculation ballot, 89% voted in favor of the SNOMED CT structure as
an ANSI standard.

And, from the perspective of the FDA's need for harmonization with ICH
and WHO, data collected using SNOMED CT can be mapped to classification
systems such as MedDRA for regulatory reporting.

# 

# 

# 

# 

# **CONCLUSION**

In summary, we urge the agency to recommend a terminology standard for
the collection of safety data that is a broad integrated whole, such as
SNOMED CT, not a narrow data set or domain specific terminology and
classification scheme such as MedDRA. The decision of an appropriate
terminology for statistical analysis and regulatory harmonization should
be considered separately.

SNOMED CT would enable the collection and analysis of comparative data
from the diverse groups reporting events as part of the framework for
building a comprehensive risk assessment and management system for drug
safety. The data collected using SNOMED CT could be repurposed by
mapping to MedDRA when needed for statistical purposes and regulatory
harmonization.

The strengths and benefits of SNOMED as a recognized leader in clinical
terminology have been demonstrated over the span of 40 years. The CAP is
clearly a strong advocate for high quality, cost effective patient care
as shown through its long term commitment to the on-going development of
SNOMED as a comprehensive, broad based terminology. As an organization
the CAP envisioned the importance of standardized terminology to support
quality care and patient safety. Therefore, it has continued to enhance
the structure and expand the scope and global use of SNOMED to ensure
that it is scientifically accurate and representative of the practice of
medicine worldwide.

We would welcome the opportunity to work with the agency toward this
end.

> Appendix 1
>
> ![](media/image5.wmf)

**Appendix 2: SNOMED CT Content**

+----------------+------------------------+-------------+------------+
| **Domain       | #####                  | **Approx.   | **Approx.  |
| Area**         | Example Concepts/Terms | Number      | Number     |
|                |                        | Concepts**  | Terms\***  |
+----------------+------------------------+-------------+------------+
| Clinical       | Rheumatoid Arthritis   | 71,000      | 188,000    |
| disorders      |                        |             |            |
| (diagnoses)    | Coronary Artery        | (All        |            |
|                | Disease                | diseases)   |            |
|                |                        |             |            |
|                | Spiral Fracture of the |             |            |
|                | Humerus                |             |            |
|                |                        |             |            |
|                | Paranoid Schizophrenia |             |            |
+----------------+------------------------+-------------+------------+
| Subjective     | Fatigue                | 837         | 2057       |
| symptoms       |                        |             |            |
|                | Lower Back Pain        | The number  |            |
|                | Radiating to Foot      | represents  |            |
|                |                        | the set of  |            |
|                | Vertigo                | findings    |            |
|                |                        | that can    |            |
|                | Numbness               | either be   |            |
|                |                        | reported by |            |
|                |                        | the patient |            |
|                |                        | or observed |            |
|                |                        | by an       |            |
|                |                        | external    |            |
|                |                        | observer,   |            |
|                |                        | and where   |            |
|                |                        | it could be |            |
|                |                        | either, we  |            |
|                |                        | categorize  |            |
|                |                        | these       |            |
|                |                        | simply as   |            |
|                |                        | findings    |            |
|                |                        | (see        |            |
|                |                        | below).     |            |
+----------------+------------------------+-------------+------------+
| Observed       | S3 Gallop              | 38,000      | 91,000     |
| findings       |                        |             |            |
|                | Tenderness in Right    | (All        |            |
|                | Lower Quadrant         | findings)   |            |
|                |                        |             |            |
|                | Maculopapular Rash     |             |            |
|                |                        |             |            |
|                | Papilledema            |             |            |
+----------------+------------------------+-------------+------------+
| Procedures     | Sigmoidoscopy          | 38,000      | 95,000     |
| performed by   |                        |             |            |
| clinicians     | Urinary                | (Total      |            |
| (preventive,   | Catheterization\       | procedures  |            |
| diagnostic,    | Hip Arthroplasty       | minus lab   |            |
| and            |                        | and         |            |
| therapeutic)   | FEV-1 Test             | imaging)    |            |
+----------------+------------------------+-------------+------------+
| Laboratory     | Serum Potassium Level\ | 25,000      | 64,000     |
| tests and test | CSF Culture            |             |            |
| results,       |                        | (Lab        |            |
| including      | Hepatitis B Surface    | procedures  |            |
| specimen       | Antigen RIA            | plus lab    |            |
| types, testing |                        | test        |            |
| methods, and   |                        | findings,   |            |
| m              |                        | specimens   |            |
| icro-organisms |                        | and         |            |
|                |                        | mic         |            |
|                |                        | rooganisms) |            |
+----------------+------------------------+-------------+------------+
| Radiology      | Abdominal CT Scan      | 3000        | 7000       |
| tests and test |                        |             |            |
| re             | Chest X-Ray            | (Imaging    |            |
| sults/findings |                        | procedures  |            |
|                | Mammogram              | plus        |            |
|                |                        | radiologic  |            |
|                | Thyroid Scan           | findings)   |            |
+----------------+------------------------+-------------+------------+
| Anatomical     | Fibula                 | 26,000      | 75,000     |
| structures     |                        |             |            |
|                | Cerebellum             |             |            |
|                |                        |             |            |
|                | Facial Nerve           |             |            |
|                |                        |             |            |
|                | Vertebral Artery       |             |            |
+----------------+------------------------+-------------+------------+
| Medications    | Glucophage             | 16,500 in   | 53,409 in  |
|                |                        | the SNOMED  | the SNOMED |
|                | lisinopril             | CT core     | CT core    |
|                |                        |             |            |
|                | Benadryl               | 13,531 in   | 32,846 in  |
|                |                        | the US Drug | the US     |
|                |                        | extension   | Drug       |
|                |                        |             | Extension  |
|                |                        | 40,722 in   |            |
|                |                        | the UK Drug | 82,808 in  |
|                |                        | extension   | the UK     |
|                |                        |             | Drug       |
|                |                        |             | Extension  |
+----------------+------------------------+-------------+------------+
| Chemical       | Vaccines               | 23,000      | 59,000     |
| substances     |                        |             |            |
| other than     | Toxins                 |             |            |
| medications    |                        |             |            |
|                | Contrast Agents        |             |            |
+----------------+------------------------+-------------+------------+
| Medical        | Pacemaker              | 2000        | 5000       |
| devices and    |                        |             |            |
| supplies       | Heart Valve Prosthesis |             |            |
| relevant to    |                        |             |            |
| the            | Greenfield Filter      |             |            |
| documentation  |                        |             |            |
| of clinical    | Indwelling Catheter    |             |            |
| care           |                        |             |            |
|                | Ventilator             |             |            |
+----------------+------------------------+-------------+------------+
| Social and     | Marital Status Values  | 5000        | 11,000     |
| c              |                        |             |            |
| are-management | Occupations            |             |            |
| concepts       |                        |             |            |
|                | Healthcare Facility    |             |            |
|                | Types                  |             |            |
+----------------+------------------------+-------------+------------+
| Standardized   | Glasgow Coma Scale     | 2000        | 4000       |
| assessment     | Components             |             |            |
| tools          |                        |             |            |
|                | APGAR Score Components |             |            |
|                |                        |             |            |
|                | Hamilton Depression    |             |            |
|                | Inventory Questions    |             |            |
+----------------+------------------------+-------------+------------+

**Appendix 3:**

**Example U.S. Drug Labeling Content vs. SNOMED**

**Event type: Adverse reaction to drug (SCT ID 62014003)**

**Causitive agent: Moricizine (SCTID 108488000)**

**Associated findings:**

+----------+------------------------+---------------------+----------+
| **ID**   | **Field1**             | **Field2**          | **       |
|          |                        |                     | Field3** |
+----------+------------------------+---------------------+----------+
| 1        | CARDIOVASCULAR         | #                   | V        |
|          |                        | ### SNOMED CT terms | ariation |
+----------+------------------------+---------------------+----------+
| 2        | palpitation            | Palpitations        |          |
+----------+------------------------+---------------------+----------+
| 3        | sustained ventricular  | Ventricular         | Y        |
|          | tachycardia            | tachycardia         |          |
+----------+------------------------+---------------------+----------+
| 4        | cardiac chest pain     | Cardiac chest pain  |          |
+----------+------------------------+---------------------+----------+
| 5        | CHF                    | Congestive heart    |          |
|          |                        | failure             |          |
+----------+------------------------+---------------------+----------+
| 6        | cardiac death          | Death               | Y        |
+----------+------------------------+---------------------+----------+
| 7        | hypotension            | Hypotension         |          |
+----------+------------------------+---------------------+----------+
| 8        | hypertension           | Hypertensive        | Y        |
|          |                        | disease             |          |
+----------+------------------------+---------------------+----------+
| 9        | syncope                | Syncope             |          |
+----------+------------------------+---------------------+----------+
| 10       | supraventricular       | Supraventricular    |          |
|          | arrhythmias            | arrhythmias         |          |
+----------+------------------------+---------------------+----------+
| 11       | atrial fibrillation    | Atrial fibrillation |          |
+----------+------------------------+---------------------+----------+
| 12       | atrial flutter         | Atrial flutter      |          |
+----------+------------------------+---------------------+----------+
| 13       | cardiac arrest         | Cardiac arrest      |          |
+----------+------------------------+---------------------+----------+
| 14       | bradycardia            | Bradycardia         |          |
+----------+------------------------+---------------------+----------+
| 15       | pulmonary embolism     | Pulmonary embolism  |          |
+----------+------------------------+---------------------+----------+
| 16       | myocardial infarction  | Myocardial          |          |
|          |                        | infarction          |          |
+----------+------------------------+---------------------+----------+
| 17       | vasodilation           | Peripheral vascular | Y        |
|          |                        | dilation            |          |
+----------+------------------------+---------------------+----------+
| 18       | cerebrovascular events | Cerebrovascular     | Y        |
|          |                        | accident            |          |
+----------+------------------------+---------------------+----------+
| 19       | thrombophlebitis       | Thrombophlebitis    |          |
+----------+------------------------+---------------------+----------+
| 20       | CNS                    |                     |          |
+----------+------------------------+---------------------+----------+
| 21       | dizziness              | Dizziness           |          |
+----------+------------------------+---------------------+----------+
| 22       | headache               | Headache            |          |
+----------+------------------------+---------------------+----------+
| 23       | fatigue                | Fatigue             |          |
+----------+------------------------+---------------------+----------+
| 24       | hypesthesias           | Hypesthesia         |          |
+----------+------------------------+---------------------+----------+
| 25       | asthenia               | Asthenia            |          |
+----------+------------------------+---------------------+----------+
| 26       | nervousness            | Nervousness         |          |
+----------+------------------------+---------------------+----------+
| 27       | paresthesias           | Paresthesia         |          |
+----------+------------------------+---------------------+----------+
| 28       | sleep disorder         | Sleep disorder      |          |
+----------+------------------------+---------------------+----------+
| 29       | tremor                 | Tremor              |          |
+----------+------------------------+---------------------+----------+
| 30       | anxiety                | Anxiety             |          |
+----------+------------------------+---------------------+----------+
| 31       | depression             | Depression          |          |
+----------+------------------------+---------------------+----------+
| 32       | euphoria               | Euphoria            |          |
+----------+------------------------+---------------------+----------+
| 33       | confusion              | Confusion           |          |
+----------+------------------------+---------------------+----------+
| 34       | somnolence             | Somnolence          |          |
+----------+------------------------+---------------------+----------+
| 35       | agitation              | Agitation           |          |
+----------+------------------------+---------------------+----------+
| 36       | seizure                | Seizure             |          |
+----------+------------------------+---------------------+----------+
| 37       | coma                   | Coma                |          |
+----------+------------------------+---------------------+----------+
| 38       | abnormal gait          | Abnormal gait       |          |
+----------+------------------------+---------------------+----------+
| 39       | hallucinations         | Hallucination       |          |
+----------+------------------------+---------------------+----------+
| 40       | nystagmus              | Nystagmus           |          |
+----------+------------------------+---------------------+----------+
| 41       | diplopia               | Diplopia            |          |
+----------+------------------------+---------------------+----------+
| 42       | speech disorder        | Speech and language | Y        |
|          |                        | disorder            |          |
+----------+------------------------+---------------------+----------+
| 43       | akathisia              | akathisia           |          |
+----------+------------------------+---------------------+----------+
| 44       | memory loss            | Memory loss         |          |
+----------+------------------------+---------------------+----------+
| 45       | ataxia                 | Ataxia              |          |
+----------+------------------------+---------------------+----------+
| 46       | GU                     |                     |          |
+----------+------------------------+---------------------+----------+
| 47       | abnormal coordination  | Coordination        | Y        |
|          |                        | problem             |          |
+----------+------------------------+---------------------+----------+
| 48       | dyskinesia             | Dyskinesia          |          |
+----------+------------------------+---------------------+----------+
| 49       | vertigo                | Vertigo             |          |
+----------+------------------------+---------------------+----------+
| 50       | tinnitus               | Tinnitus            |          |
+----------+------------------------+---------------------+----------+
| 51       | GI                     |                     |          |
+----------+------------------------+---------------------+----------+
| 52       | nausea                 | Nausea              |          |
+----------+------------------------+---------------------+----------+
| 53       | abdominal pain         | Abdominal pain      |          |
+----------+------------------------+---------------------+----------+
| 54       | dyspepsia              | Dyspepsia           |          |
+----------+------------------------+---------------------+----------+
| 55       | vomiting               | Vomiting            |          |
+----------+------------------------+---------------------+----------+
| 56       | diarrhea               | Diarrhea            |          |
+----------+------------------------+---------------------+----------+
| 57       | anorexia               | Anorexia            |          |
+----------+------------------------+---------------------+----------+
| 58       | bitter taste           | Primary bitter      | Y        |
|          |                        | taste disorder      |          |
+----------+------------------------+---------------------+----------+
| 59       | dysphagia              | Dysphagia           |          |
+----------+------------------------+---------------------+----------+
| 60       | flatulence             | Flatulence          |          |
+----------+------------------------+---------------------+----------+
| 61       | ileus                  | Ileus               |          |
+----------+------------------------+---------------------+----------+
| 62       | urinary retention      | Urinary retention   |          |
+----------+------------------------+---------------------+----------+
| 63       | urinary frequency      | Urinary frequency   |          |
+----------+------------------------+---------------------+----------+
| 64       | dysuria                | Dysuria             |          |
+----------+------------------------+---------------------+----------+
| 65       | urinary incontinence   | Urinary             |          |
|          |                        | incontinence        |          |
+----------+------------------------+---------------------+----------+
| 66       | kidney pain            | Kidney pain         |          |
+----------+------------------------+---------------------+----------+
| 67       | impotence              | Impotence           |          |
+----------+------------------------+---------------------+----------+
| 68       | decreased libido       | Decreased libido    |          |
+----------+------------------------+---------------------+----------+
| 69       | RESPIRATORY            |                     |          |
+----------+------------------------+---------------------+----------+
| 70       | dyspnea                | Dyspnea             |          |
+----------+------------------------+---------------------+----------+
| 71       | hyperventilation       | Hyperventilation    |          |
+----------+------------------------+---------------------+----------+
| 72       | apnea                  | Apnea               |          |
+----------+------------------------+---------------------+----------+
| 73       | asthma                 | Asthma              |          |
+----------+------------------------+---------------------+----------+
| 74       | pharyngitis            | Pharyngitis         |          |
+----------+------------------------+---------------------+----------+
| 75       | cough                  | Cough               |          |
+----------+------------------------+---------------------+----------+
| 76       | sinusitis              | Sinusities          |          |
+----------+------------------------+---------------------+----------+
| 77       | MISCELLANEOUS          |                     |          |
+----------+------------------------+---------------------+----------+
| 78       | sweating               | Sweating            |          |
+----------+------------------------+---------------------+----------+
| 79       | musculoskeletal pain   | Musculoskeletal     |          |
|          |                        | pain                |          |
+----------+------------------------+---------------------+----------+
| 80       | dry mouth              | Dry mouth           |          |
+----------+------------------------+---------------------+----------+
| 81       | blurred vision         | Blurred vision      |          |
+----------+------------------------+---------------------+----------+
| 82       | drug fever             | Drug fever          |          |
+----------+------------------------+---------------------+----------+
| 83       | hypothermia            | Hypothermia         |          |
+----------+------------------------+---------------------+----------+
| 84       | temperture intolerance | Body temperature    | Y        |
|          |                        | finding             |          |
+----------+------------------------+---------------------+----------+
| 85       | eye pain               | Pain in eye/ Pain   | Y        |
|          |                        | around eye          |          |
+----------+------------------------+---------------------+----------+
| 86       | rash                   | Rash                |          |
+----------+------------------------+---------------------+----------+
| 87       | pruritus               | Pruritus            |          |
+----------+------------------------+---------------------+----------+
| 88       | dry skin               | Dry skin            |          |
+----------+------------------------+---------------------+----------+
| 89       | urticaria              | Urticaria           |          |
+----------+------------------------+---------------------+----------+

Appendix 5

![](media/image1.wmf)

[^1]: Building the Information Core-

    Implementing the NHS Plan January 2001

[^2]: "Object-Oriented Modeling and Terminologies for Drug
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[^3]: "The Content Coverage of Clinical Classifications", JAMIA 1996;
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[^4]: "Phase II Evaluation of Clinical Coding Schemes: Completeness,
    Taxonomy, Mapping, Definitions and Clarity", JAMIA, 1997; 3:238-251.