Medical Writing

MEDICAL WRITING
‘If it is not recorded it did not happen’
[A frequently repeated saying for documentation]


Introduction
1. A Doctor’s writing is proverbially said to be readable only by dispensers. I am not sure whether this has ever been researched. But there is no doubt that medical writing does require deciphering. I am also not sure if the doctor’s wife really needed the pharmacist’s help for deciphering the love letters. But surely help would not have been required if doctor had developed the skill of good medical writing and wife had learnt to understand the jargon used by doctor.

2. Clinical research is required to be documented for approval, conduct and acceptance by regulatory authorities. Various documents like protocol, case report form (CRF) and study report are required to be completed. Everyone connected with clinical research has to understand the process and present it skillfully. That requires good medical writing. Hence it is important for everyone connected with clinical research. The responsibility of preparing documents rests with principal investigator and sponsors. They need help. Good medical writers are hence in demand. Good medical writing is an art and skills need to be developed for this. This paper attempts to describe the essential skills for good medical writing.

Definition
3. Medical writing can be defined as “Understanding the clinical process and presenting it skillfully’. Other definition could be ‘Art of presenting a scientific work in words’. The purpose of medical writing is to plan the study, keep case records, analyze the findings and publish them. Protocol, which specifies objectives and methodology of clinical research, is one of the very important medical documents. So a separate module is included in the course for protocol design. In short every medical communication is medical writing. For clinical research medical writing is the link between observation and data generation. All data for analysis comes from case record forms (CRF). Clinical research workers have to analyze the data and not only transcribe it. Hence they require better understanding of medical writing than those doing medical transcriptions.

Objectives
4. The objectives of medical writing are given in the definition. For clinical research the objectives are:
a. Present the plan for research (Protocol, Application)
b. Maintenance of case records (CRF)
c. Converting the case records into data
d. Documentation of work for regulatory approval (Study Report)
e. Documentation proving adherence to GCP (SOP, Consent form)
f. Research publication (Paper writing)
5. The medical documentation can be classified according to its objective as given above. To fulfill the objectives each type of writing will have some special characteristic. It will be discussed separately. First we will try to understand the common requirements for good medical writing.
6. All stake holders in medical research, namely research workers, regulators, patients (participants), sponsors, competitors, and the beneficiary (society) need to read medical papers some time or other. Some documents are meant for regulators (protocol) while others may be primarily for patients (consent form). Beneficiaries and peers are interested in published reports. Target reader’s interest and capabilities of understanding needs to kept in mind while preparing these documents. Sometimes the requirements may be contradictory. One example is the contradiction between confidentiality and transparency. Both are pillars of ethical practices/ GCP and have their own place and importance. CRF is confidential but transparency is essential for data to be considered as authentic. Sponsors like to underplay the adverse events but its knowledge is very important for beneficiary. This needs to be understood and appreciated. For being effective, medical documents must be prepared keeping such requirements and target reader in mind.

Ingredients
7. What ever is important must be documented. That is the saying quoted at the start of this paper. It emphasizes that documents must be complete and through. The essentials or ingredients for good medical writing can be laid out from the understanding of the objectives and target population. We will then not need the ‘dispenser’ but will of course need a medical dictionary.
8. Medical writing, like any other means of communication needs to be learnt, understood and practiced for being effective. Good working ‘medical knowledge’ is the backbone of documentation and effect comes from good communication skills. You can judge this paper on these criteria and improve it later.
9. Reliability is one aspect, which can never be over emphasized. No research is valuable if ethical principles have not been adhered to. Examples of shady work are innumerable. ‘Nuremberg Trial’ and ‘Tuskegee Syphilis Study’ are well known. You can refer to the website ‘the talking drum. com’ for some more interesting information on unethical practices labeled as human genocide. Recent Indian examples are trial of Ragaglitazar, by Novo Nordisk, streptokinase trial by Shantha Biotech, modified insulin trial by Biocon and Letrozole promoted by Sun Pharma for use as a fertility treatment. You can refer to these in various articles published including those by Scot Carney (Dec 2005) and Sandhy Shrinivasan (Sep 2004) available on the net.

10. The ingredients of good medical writing can hence be listed below:
a. Fluency of language
b. Comprehension of human physiology and pharmacology
c. Understanding medical terminology
d. Use of ‘standard terms’ from specified sources
e. Knowledge of regulatory requirements
f. Learning the language of the ‘tools’ used
g. Awareness of target reader of the document
h. Demonstrated following of GCP/ value systems
11. We will try and cover these in subsequent paragraphs. Of course a lot of this is common sense. But then common sense is rare. In the syllabus also there is a topic on ‘common sense guidelines’. This paper is not a complete treatise on medical writing. It is only an introduction to the subject. Very Good literature is available on all these aspects. Some references are listed at the end of this paper. Regulatory authorities have taken care to issue guidelines for every step. I will request you all to go through all these especially the requirements given by the regulators without which no approvals can be received.

Fluency of language (writing)
12. Availability of manpower with skills in English is counted as one of the advantages for India. It is one of the reasons for the clinical research being allocated to our country by global firms. If you do not fit the bill you naturally tend to loose out. Writing skills do appear to be deteriorating. Pride in the regional language called as ‘own language’ appears to be one reason. But surely it should not be considered same as pride in speaking or writing poor English. Some advertising culture like ‘Khokho Patil’ and ‘Munna Bhai’ has also contributed to deterioration of English speaking skills. The writing skills have suffered due to the SMS culture also. I have used an abbreviation, which I assume you know. But I want to emphasize that I have followed a wrong practice. SMS may be taken as ‘short man syndrome’ or ‘single male service’. If you want to use acronyms or abbreviations please do it after explaining it. Suffice to say that one needs to give attention and develop good command over English. It is the language in use for clinical research and will be so in foreseeable future.
13. For medical writing the language has to be simple, precise and devoid of jargons. There are enough complicated words in medical terminology. Do not add any more. ‘Pun’ makes good humor but is bad medical writing. Coining new words, the present trend in newspaper reporting, will attract attention but may be the cause for refusal of permission.

Comprehension of human physiology and pharmacology
14. The mechanism of drug action is covered in pharmacology. The two words: ‘Pharmacokinetics’ and ‘Pharmacodynamics’ will be repeated often enough during your course. So I will try and cover some basic aspects of human physiology and drug pharmacology.

Pharmacology: Drug action and metabolism
15. Pharmacology deals with the mechanism of action of drugs in all its aspects. The process of absorption, maintenance of effective concentration in blood, delivery at the target (site of action), breakdown and finally excretion is called as drug metabolism. Hepatic cells (Liver) breakdown the drug into its metabolites through enzyme: Cytochrome P 450 system. They are then excreted either by kidneys, gastro – intestinal system or respiratory system. At the target site drug or its effective metabolite enters the cells through specific receptors. This is an active process and does not occur by simple diffusion. In some cases even absorption from gut is an active process requiring specific receptors to which the drug binds for absorption and circulation. Most drugs act by stimulating or depressing some enzyme system responsible for the function. Drugs circulate all over the body and their reach is not restricted to target organs only. They may sometimes produce harmful effects on reaching the organs or cells, which are not targeted. For example the anticancer drug not only kill the cancerous cells but also the normally dividing cells. This is called as drug toxicity or adverse drug reaction (ADR).
16. Pharmacokinetics is defined as quantification of drug and metabolite concentrations in the body as a function of time. It gives an idea of what the body does to the drug (Dr Baliga). Pharmacodynamics on the other hand is defined as quantifying the drug action as a function of the drug or metabolite concentration (or administered dose). It gives an idea of what the drug does to the body (Dr Baliga). I will draw your attention to an excellent presentation by Dr Baliga on this subject. It is available on our computers. These studies are done on animals before human clinical trials and are also studied in phase I trials. Now these studies can be done in vitro on tissue cultures and also by computer modeling (simulators). This saves time in pre - clinical studies.

Use of ‘standard terms’ from specified sources
17. A very important use of medical writing is for generation of data. Coding the medical records does this. Coding can be defined as conversion of text (verbatim record) to standardized terminology for statistical analysis. This reduces diversity in data. For example, reduced blood pressure, low BP, and fall in blood pressure all mean ‘hypo-tension’. Stomach pain, abdominal pain and stomachache all have same meaning. By using only one standard term for all such texts improves the accuracy and efficiency of the data.

18. Many coding dictionaries are available for this purpose. These include: a. MedDRA: Medical Dictionary for Regulatory activities
b. WHODD: World Health Organization Drug Dictionary
c. WHOART: World Health Organization Adverse Reaction Terms
d. COSTART: FDA’s coding symbols for a thesaurus of Adverse Reaction terms
e. ICD 9 CM: International classification of Diseases 9th Revision

19. MedDRA: Following lines are extracted from first chapter of MedDRA.
I quote:
“The Medical Dictionary for Regulatory Activities (MedDRA) was designed for the specific use of sharing regulatory information for human medical products. However, unless users can achieve consistency in the way they assign particular terms to particular symptoms, signs, diseases, etc., the new terminology will yield little improvement over the divergent practices of the past. This Points to Consider document is an ICH-endorsed guide for MedDRA users. It is designed to be updated based on MedDRA changes, and is a companion document to the MedDRA Terminology. It was developed and is maintained by a working group charged by the ICH steering committee consisting of regulatory and industry representatives of the European Union, Japan and the United States, as well as representatives from Canada, the MedDRA Maintenance and Support Services Organization (MSSO), and Japanese Maintenance Organization (JMO). Specific examples contained in this document are based on MedDRA version 5.0.

“1.1 Objective of this document
The objective of this ICH Points to Consider document is to promote consistent term selection. Organizations are encouraged to document their term selection strategies, methods, and quality assurance procedures in organizational–specific coding guidelines, which should be consistent with the Points to Consider document. Consistency in term selection will promote medical accuracy when using MedDRA to share data worldwide. This will in turn facilitate a common understanding of data shared across and/or between academic, commercial and regulatory entities. The document could also be used by healthcare professionals, researchers and other interested parties outside of the regulated pharmaceutical/biological industry. The document is intended to provide term selection advice where it is needed either for a business purpose or regulatory requirement. There may be examples that do not reflect practices or requirements in all regions; this document does not intend to communicate specific regulatory reporting requirements. In addition, it is expected that as experience with MedDRA increases, there will be changes to the document.” Unquote
20. A MedDRA Browser is available free and is for demonstration. You may down load this from internet and practice the use. However it is not very difficult for computer literate individuals. MedDRA is used for coding medical history, signs and symptoms as well as adverse events (AE) including adverse drug reactions (ADR). For coding of drugs however WHODD is used commonly. For classification of diseases (especially past medical history) ICD 9M is used. Please see the presentation on MedDRA available on our computer in the department.
21. Auto coding and Manual Coding: Coding can be automated. Computer will try and match the exact words given in the dictionary and code it to standard term. However exact verbal expression may not be available. In this case manually the term can be found using general medical knowledge. As a dictum however clarifications can be sought from principal investigator when in doubt. Similar sounding terms or spellings with minor variations are better clarified and queried before locking the data.

Knowledge of regulatory requirements
22. This is another aspect very important for medical writing. Presently the regulatory requirements are country specific although trials are global. ICH is an effort to bring common regulatory requirements and is gaining acceptance. Regulatory requirements have been covered in course CRM 104. I will just touch on some aspects.
Awareness of target reader of the document
23.The style of writing and contents of the paper should be chosen keeping the target reader in mind. For example applications for permission from authorities should be in persuasive tone. A paper for publication or study report must give details of methodology so that the paper can be subjected to meta - analysis. References must be sited in the style preferred by the journal. Protocol should be exhaustive and clear such that every one be it principal investigator, data recorder, sponsor, regulator or auditor is clear on objective of trial, methodology, number of participants and end point considerations. Standard Operative procedures (SOP) are meant for detailed description of procedures or specific functions and define individual responsibility. The narrative of SOP is generally in the assertive tone like passing orders.
24.It is generally a good practice to let some one else read and correct the document prepared by you. Others can judge clarity of your writing better. Since one is very clear in own mind the writing tens to be less explanatory and hence lacks clarity for others. Format for Informed Consent should be in as simple language as possible as the participant is not very educated in most cases. In fact that is one of the criticisms on trials in India.
Demonstrated following of GCP/ value systems
A saying goes that Caesar’s wife must not only be honorable but also appear to be honorable. So GCP guidelines must not only be followed but Good Clinical Practices must be documented. The sponsor has obvious financial interest in trial. Principal Investigator is knowledgeable and hence is powerful. He is also interested in positive outcome of the trial either due to financial interest or due to academic interest (vanity). Enough examples of intellectual dishonesty are available in literature. So medical writing and record keeping must give sufficient evidence that GCP have not been compromised during trial.
Principal investigator is responsible for maintaining GCP norms. He/ she is responsible even if he/she has delegated some authority to his/ her colleagues. Some times individual rights (human rights) are sacrificed on the pretext of doing good to a larger section. Does our ancient philosophy believe in this? A well - known Sanskrit verse reads like this:
“Ekam Tyajet Kulasyarthe; Gramsyarthe kulam tyajet;
Gramam Janapadasyarthe; Atmarthe prithivim tyajet”.
(Sacrifice the interest of individual for family, sacrifice the interest of one family for the interest of the village. Sacrifice the interest of village for state but for the interest of ‘Atman’ sacrifice the world.)
This may be true for defending the country but not for drug trials. If this parameter is used for clinical trials then you are sacrificing the interest of your Atman – your inner self and that is not the teaching. In any case sacrificing your self may be laudable but by compromising human rights you are you are killing some one else. That is not sacrifice but is genocide. So please make sure that you not on;y follow GCP but give enough proof of that in your documentation.

Summary
Good medical writing requires development of communication skills. Ability to express your thoughts in simple and clear terms will enhance the quality of your writing. Target reader must be kept in mind. A good knowledge of medical terms, human physiology, drug metabolism and regulatory requirements is absolutely essential. No medical writing will be acceptable if it does not demonstrate adherence to GCP norms.