The Problem with off Label and Unlicensed Medication - Article Example

Paediatrics The Problem with Off label and Unlicensed medication in Pediatrics Licensing of Medication is mandatory under the Medicines Act 1968. In the United Kingdom, the power of granting licenses vests with the Medicines Control Agency (MCA). They are shouldering this responsibility on behalf of the Ministry of Health, who are advised on such matters by an expert Committee on Safety of Medicines (CSM). When a Pharmaceutical Company wishes to apply for a manufacturing license of a particular medicine, it would, first of all, have to convince the concerned authorities, through trials and clinical tests, that the said medicine is safe for use, has sound therapeutic qualities and possesses the required quality. Only after the authorities are satisfied on these counts, is a Marketing Authorization granted. The appropriate dosage of the medicine, the age group of patients who could safely use it, the correct method of its usage, safety measures to be taken while administering the medicines etc., are envisaged in the SPC (Summary of Product Characteristics) and relevant patient details are available in PIL (Patients Information List). The manufacturers of the medicines have to strictly abide by the SPC while promoting the use of their products. But, many of the medicines used on infants and children do not have Marketing Authorization or are outside the scope of MA. These are termed as Off-label or unlicensed medication. Although the use of off label or unlicensed medicines is not illegal, serious concerns need to be voiced since the products have not met the scrutiny tests as per the licensing procedures. If products are used according to their MA, it is the pharmaceutical companies who would be held liable for harmful effects on patients, but in case of off-label and unlicensed drugs, it is the clinician and his employers who could be sued for damages, and not the manufacturers. There are risk involved “to use adult dosage forms for pediatric patients.” (Nunn 2002). Since the dosage of extemporaneous medicines may not always be correct and there may be lack of patients’ profile in the case of off- label and unlicensed medicines. Moreover, harmful drug reactions may also result. The problem with formulation of extemporaneous products The British Pharmacopocia (BP), published by the Royal Pharmaceutical Society of Great Britain, is the officially recognized standard authority for formulation of drugs. The BNF (British National Formulations) published by the BMA and RPS (Royal Pharmaceutical Society) of Great Britain also provide formulations. These are all acceptable formulations. However, an extemporaneous product is a pharmaceutical product, which has been newly compounded without prior preparation and is done in a improvised manner. Many clinical settings and dispensaries have their own special formulations, which is often used in clinical practices. The need for extemporaneous products have arisen because of the lack of proper pediatric formulations. For instance, some medicines given to children are actually formulated for injection use or tablet forms in adults (Dexamethasone), but are powdered and administered to children as Suspensions. The ill effects that may occur if an originally intended tablet is powdered and used as suspensions for oral use. However, the risk of extemporaneous products would lie solely with the pharmacists and a mere disclaimer on the part of the patient or doctor would not absolve liability. The main problem relating to the use of extemporaneous drugs would be one relating to quality, validity and shelf life. Also, the dosage should also be carefully administered in the case of extemporaneous products so that infants and children do not become therapeutic orphans. (Nunn et al 1996). Current legislation in the UK and compare this with the US The legislation in UK is called the Medicine Act 1968 which was spurred by the Thalidomide Tragedy which accounted for the loss of many young lives during the 1960s. It divides Medicinal drugs into 3 categories: prescription drugs, pharmacy drugs (which subject to certain exceptions, could be sold or supplied only through prescription and “under the supervision of the pharmacist”) (The Medicines Act 1968), and general drugs which could be sold directly to the public over the counter. However, in the US, the FDA Modernization Act and Paediatric Rule says that every new application for new product should contain “Pediatric Assessment” which provides, that the product would be “safe and effective” (Guidance for Industry Recommendations for Complying with the Paediatric Rule). The American laws regarding drugs are much stricter than in European countries and the rules “regulate advertising of unapproved uses of drugs and devices.” (History of Clinical Trials: How it all Began). How children differ from adults-physiology There is a vast difference between children and adults in the administration of medication and also among children of different age groups. Many drugs are used without being specifically tested in children or are not specifically licensed. However, the evidence on the scale of harm that off-labels and unlicensed medicines can do are often scanty and there is sufficient indications to prove that the actual cases are much more than reported. The difference in physiology between adults and young children is that young children cannot swallow tablets and therefore, they need liquid medicines. Also, their tolerance level to certain drugs levels may be higher than that of adults. The use of off-label and unlicensed medicines can put the infants into a “greater risk of toxicity.” (Choonara). Moreover, harmful drug reactions may also result. “Adverse Drug reaction in hospitalized children were more frequently associated with unlicensed and off-label drug prescriptions than with licensed ones (6% Vs 3.9%).” (Swiss Medical Weekly 2006). The importance of clinical trials in children-the current problems The main problems regarding clinical trials on children are that there are certain ‘ethical problems’ involved in it. (Fundamental & Clinical Pharmacology). While adults can be taken as volunteers for testing of adult drugs, it is only children who would have to be used for testing in case of pediatrics medicines since pediatric medicines cannot be administered on adults. Further, clinical trials on children ensure a great deal of risk. Sick children and children having rare conditions cannot be subjected to clinical tests. For the purpose of Clinical tests, the four categorization can be made: 1. Conditions affecting children exclusively 2.Conditions affecting children, or which are of special significance to children 3. Conditions occurring to both adults and to children for which currently no treatment is available and 4. Conditions occurring to both adults and to children for which other lines of treatment are available. What is currently being done to address the problem within pediatrics? There has been a Joint Medicines Committee between the Royal College of Pediatrics and Child Health & Neonatal Paediatric Pharmacists Group which has produced a book entitled “ Licensing Medicines for Children” regarding the procedures and methodology to be followed for clinical trials. There is also another book entitled “Medicines for Children” which could serve as reference book to medical professionals regarding relevant information about medicines and the circumstances and justifications for use of “off-label medicines.” The MCA has devised a plan for pediatric use and the Expert committee of CSM has formulated the use of current legislation for inducing pharmaceutical companies to submit pediatric information when requiring fresh licenses for new products and a proposal of 5 year review for established products. Finally for the benefit of Medical practitioners when prescribing pediatric drugs, a National Pediatric Information Centre has been established which would provide current information about medicines. Learning Styles There are six main types of Learning styles as follows: 1. Learning through Seeing (Visual Spatial), Learning through Hearing (Aural- Auditory), Learning through Reading (Verbal- Linguistic), Learning through Physical movements and actions (Physical – Bodily- Kinesthetic), Learning through application of logical tools and Mathematics, Learning through social – interpersonal Learning through lonely and intra person. Learning through Seeing (Visual Spatial) This form of learning is associated with images and graphical representations including Web, idea maps etc and this form of learning can increase thinking powers. Learning through seeing also involves reading the body language and facial gestures of the teacher and understanding the subject through them. The best forms of learning through sight would be seeing and interpreting visual displays like pictures, graphs, pie-charts, books, videos etc Learning through Hearing (Aural- Auditory) This form of learning is through group discussions, classroom lectures, radio programmes, audio cassettes recordings, public and private speeches etc, etc. This form of learning is when the person listens in one- to- one, or one- to- many forms of communications. Learning through Reading (Verbal- Linguistic) This form of learning involves reading books and literature on subjects and learning through them. Through this form the subject develops linguistic skills and mastery of words and makes “efforts to find the meaning of new words” for future usage. (Discover your Learning Style – Graphically). Learning through Physical movements and actions (Physical – Bodily- Kinesthetic) This form of learning involves using hands on approach, through exploration and physical actions. People who follow this form of learning cannot sit still for long and are always on the move, seeking new discoveries and activities. Learning through application of logical tools and Mathematics This form of learning inculcates use of logic and scientific analysis. This style follows set pattern of reasoning and involves numerical and mathematical applications. People who follow this form can undertake complex mental mathematical calculations easily. They are capable of making plans, procedures and prioritizing “before putting them into action”. (Discover your Learning Style – Graphically). Learning through social – interpersonal Such people are socially activated and enjoy being with people. Their learning style derives from interaction with people, listening to others and offering counsel. Learning through solitary and intra person This form of learning is learning to know oneself. Through a process of self introspection the person is able to “develop a deeper understanding of yourself.” (Discover your Learning Style – Graphically). The knowledge and learning imbibed is through knowledge of the self and relating oneself to others harmoniously. Multiple choice and Free response As the term suggests, multiple choice would be when the examinee has to exercise his choice among the alternatives given, after careful thinking and reasoning whereas in free response, he has to give his own interpretations based on his knowledge and use of intelligence and discretion. While in multiple choice he has to only choose the right answer, in free response he has to first know the right answer and then answer it. The Advantages of Multiple Choice are: The examinee only needs to pick the right answer from a certain number of choices. So with an element of luck and guesswork he may get the right answer. The law of elimination would be possible .If the examinee is convinced that 3 of the four answers are wrong; he can easily pick up the right one. Where speed and accuracy matters, the multiple choice would be the right choice and also a good examinee can get full marks if he is able to solve all the questions correctly. The multiple-choice answers equip the person for competitive spirit. The Disadvantages of Multiple choice would be that it leaves no element of doubt and should the examinee be wrong, he would lose all his marks for that question. Another aspect is that in his nervousness, he may misread or miswrite the answer and thus lose marks. Also multiple choices involve negative markings for wrong answers. Coming to the advantages of free response, if the answer is somewhat correct, the examinee would get some marks instead of no markings as in multiple type. In free response the examinee has more time to reflect and frame his answers and thus can get better marks. Working in a planned and organized way would definitely help in free response answers. Where lengthy answering is required it is better to go for free responses. The disadvantages of free response is that a lot depends upon the psyche of the examiner while evaluating the answer scripts. If the style of writing and flow impresses the reader, the examinee gets good marks, but otherwise he may be put to disadvantage. Again, free response is not as scientific and clear cut as multiple choice and could leave a lot of scope for errors. Work Cited Nunn, Tony. B. Pharm, FRPharmS. 2002. Using Unlicensed and Off-Label Medicines. http://www.dial.org.uk/docs/topics-unlicensedmedicines.pdf (accessed on April 8, 2007). Unlicensed and Off-Label Drug Use in a Swiss Paediatric University Hospital. A Plot Study. http://www.smw.ch/docs/pdf200x/2006/13/smw-11275.PDF (accessed on April 8, 2007). Nunn, Tony., Hull, David. 1996. Unlicensed Medicines-Is There a Problem? Priory Lodge Education Ltd. http://www.priory.com/paeds/pwk5.htm (accessed on April 8, 2007). Choonara, Imti. Chapter 5. Paediatric Drug Research. http://www.iuphar.org/pdf/hum_34.pdf (accessed on April 8, 2007). The Medicines Act 1968. The Shipman Inquiry. http://www.the-shipman-inquiry.org.uk/4r_page.asp?id=3116 (accessed on April 8, 2007). Guidance for Industry Recommendations for Complying with the Paediatric Rule (21 CFR 314.55(a) and 601.27(a)). FDA/ Centre for Drug Evaluation and Research 2000. http://www.fda.gov/cder/guidance/3578dft.htm (accessed on April 8, 2007). Discover your Learning Style – Graphically. http://www.learning-styles-online.com (accessed on April 8, 2007). History of Clinical Trials: How it all Began. http://www.healthandage.com/html/res/clinical_trials/content/section1.htm (accessed on April 8, 2007). Fundamental & Clinical Pharmacology. Volume 17 Issue 1 Page 125 – February 2003. http://www.blackwell-synergy.com/doi/abs/10.1046/j.1472-8206.2003.00123.x (accessed on April 8, 2007). Read More