BASO pyramid in Medical writing

Baseline: correct grammar and spelling, accepted terminology in the field

Style: personal sty l e,language styles,type of manuscript,“house style” of specific journal,conventions, traditions

Opinion: It is important to realize that there is, in fact, room for personal opinion even in the context of scientific writing. This implies that certain issues are not simply “correct” or “incorrect.”

Medical writing- Thomas Mann urge

Many scientific authors hold a firm belief that sentences crowded with information add value to their scientific message, and yet they achieve the opposite. Although this problem is evident across the entire
scientific literature, it is clearly more pronounced among authors with a language background other than English, for example, German or French. The temptation to use ample decoration also comes from the mixing of creative and scientific writing is termed as Thomas Mann urge.

MedDRA Changes - General Remarks

There are two possible types of changes in the MedDRA terminology: simple changes and complex changes. Simple changes are changes to the existing terminology that involve terms at the PT and LLT levels. There are two types of Simple changes: (1) changes introduced by subscribers request and (2) Maintenance changes (also referred to as Associate changes). Maintenance changes are generated as a by-product of other changes requested by subscribers, or changes introduced by the MedDRA Management Board to preserve consistency within the dictionary. Complex changes involve modifications within the entire hierarchy, including the HLT, HLGT, and SOC terminology. Currently, the initial MedDRA terminology version release in one specific year (12.0, 13.0) includes both simple and complex changes, and the subsequent release in the same year (12.1, 13.1) represents a simple change of terminology. These changes are based on MedDRA subscribers' terminology change requests and on MedDRA terminology maintenance needs identified by MedDRA's maintenance organization reviewers. Please note that as a consequence of implementing some of these changes (e.g. demoting a multi-axial PT, adding a new HLT, etc.) it may be necessary to break the multiaxial links, to re-link the replacement terms, and/or to enable additional terms to be included within a particular SOC. All these changes may require modifications to your existing MedDRA coding, guideline development, and data retrieval practices. Keep in mind that changes involve both MedDRA terminology updates as well as Standardized MedDRA Queries (SMQ).

Reference: MSSO

Common Terminology for Adverse Events (CTCAE)- National Cancer Institute

Grading adverse events : By this grading scale, all adverse events are classified as follows:

0=No adverse event or within normal limits
1=Mild adverse event
2=Moderate adverse event
3=Severe and undesirable adverse event
4=Life-threatening or disabling adverse event
5=Death related to adverse event

Individual Safety Case (ICSR) Processing

This involves data entry; data QC check; medical review; reportability assessment; electronic/paper reporting; follow up; case closure; case file archiving.

This can be performed for post-marketing and clinical trial cases (SAEs and SUSARs) and captured within the validated and password protected adverse event safety database. Reports can be generated electronically (or paper format) to the Regulatory Agencies from this database and compliance metrics produced for Companies for notification of adherence to the regulations.
Similarly the database can generate, periodic summary tabulations; line-listings and perform analyses for identifying potential signals and tabulations and specialized queries used in safety reviews.

They are responsible for obtaining follow up information to adverse reaction (ADR) reports to obtain comprehensive information that will allow a proper determination of both causality and the possible mechanism by which the reaction occurred thereby looking to prevent or minimize its appearance.

Source: EMEA Guidelines

Development Safety Update Report( DSUR)

The main focus of the DSUR is data from interventional clinical trials (referred to in this document as “clinical trials”) of investigational drugs including biologicals, with or without a marketing approval, whether conducted by commercial or non-commercial sponsors.It presents an annual review and evaluation of pertinent safety information collected during the reporting period to:

1)summarise the current understanding and management of identified and potential risks;
2)describe new safety issues that could have an impact on the protection of clinical trial subjects;
3)examine whether the information obtained by the sponsor during the reporting period is in accord with previous knowledge of the product’s safety; and
4)provide an update on the status of the clinical investigation/development programme. This guideline defines the content and format of a DSUR and provides an outline of points to be considered in its preparation and submission.

DSUR cannot be considered as:

a)An evaluation of the benefit-risk relationship for the product
b)An interim integrated safety summary (ISS) as submitted for marketing applications
c)A repository or discussion of individual adverse experience cases, unless by exception
d)A signal detection tool
e)An “expert report”

Reference: ICH E2F

Adverse Drug Reactions Classifcations

Classification based on frequency :

a)Very common : > 1/10 ( > 10%)

b)Common (frequent):  > 1/100 and < 1/10 ( > 1% and < 10%)

c)Uncommon (infrequent): > 1/1,000 and < 1/100 ( > 0.1% and < 1 %)

d)Rare:  > 1/10,000 and < 1,000 ( > 0.01% and < 0.1%)

e)Very rare:  < 1/10,000 (< 0.01%)

Adverse Drug Reactions Classifcations: Based on Severity

a)Mild : No antidote or treatment is required; hospitalization is not prolonged

b)Moderate: A change in treatment (e.g., modified dosage, addition of a drug), but not necessarily discontinuation of the drug, is required; hospitalization may be prolonged, or specific treatment may be required

c)Severe: An ADR is potentially life threatening and requires discontinuation of the drug and specific treatment of the ADR

d)Lethal : An ADR directly or indirectly contributes to a patient's death

Medical Coding in Clinical Trials

All data generated in Clinical  trials are ultimately subjected to further analysis. It is very essential that this data gets interpreted uniformly in a standardized format.Medical coding is performed in clinical trial using Standardised medical coding dictionaries.Data listed above like AEs, SAEs, MH , CM and any other category generally are coded. However coding AEs, SAEs and CM is mandate in any given clinical trial.

There are several standardized medical coding dictionaries in the market; however five dictionaries listed below are used for coding:
1. COSTART - Coding Symbols for Thesaurus of Adverse Reaction Terms
2. ICD9CM - International Classification of Diseases 9 Revision Clinical Modification
3. MedDRA – Medical Dictionary for Regulatory Activities
4. WHO-ART – World Health Organisation Adverse Reactions Terminology
5. WHO-DDE– World Health Organisation Drug Dictionary Enhanced

Out of the above five, two widely used medical coding dictionaries used for coding medical terms generated in clinical trials are MedDRA and WHO-DDE.

CCSI(Company Core Safety Information)

All relevant safety information contained in the company core data sheet (CCDS) prepared by the marketing authorization / licence holder and which the MA holder requires to be listed in all countries where the company markets the drug, except when the local regulatory authority specifically requires a modification

The CCSI is the reference information by which listed and unlisted are determined for the purpose of periodic reporting for marketed products, but not by which expected and unexpected are determined for expedited reporting.

For the purpose of periodic Safety Update Report, the CCSI forms the basis for determining whether an ADR is already listed or is still unlisted.

For a clinical trial, the CCSI is the company core data sheet, prepared by the MAH of a marketed product when it is used as an investigational medicinal product, except when the local regulatory authority specifically requires a modification. For investigational products the CCSI is the Development Core Safety Information.

Literature Database- Difference between Medline and Embase Database

MEDLINE (Medical Literature Analysis and Retrieval System Online) is a bibliographic database of life sciences and biomedical information.It is compiled by the United States National Library of Medicine (NLM).MEDLINE uses Medical Subject Headings (MeSH) for information retrieval. Engines designed to search MEDLINE (such as Entrez and PubMed) generally use a Boolean expression combining MeSH terms, words in abstract and title of the article, author names, date of publication.It mainly covers US journals.

Embase(Excerpta Medica), is a biomedical and pharmacological database produced by Elsevier.It tends to be more comprehensive with inclusion of more EU journals (plus US journals) as well as abstracts of scientific meetings, which you would not find in MedLine.