Pharmacoepidemiological and pharmacoeconomic aspects of untoward reactions of medicines: a latent pr

1
Pharmacoepidemiological and pharmacoeconomic
aspects of untoward reactions of medicines a
latent problem and hidden healthcare expenditures

• Elena Ovchinnikova
• Candidate Medical Sciences
• Quality Supervising Officer,
• Research Center for Testing Medicines
• Federal State Office, Roszdravnadzor

2
Pharmacoeconomics/pharmacoepidemiology

• Pharmacoepidemiology focused on researching
  medicines and their effects at the level of
  populations
• Pharmacoeconomics focused on researching
  clinical and economic benefits of using medicines
  and medicines therapy schemes

3
Phases of obtaining epidemiological data on UR

• Terminology and protocol of study
• Identification
• Registration
• Proving dependence
• Classification

4
Sources of epidemiological data

• Pre-registration pre-registration CS
• Post-registration
• Post-registration CS
• Method of spontaneous informing ?????????
• Monitoring medical treatment and prevention
  institutions, retrospective and prospective
• Monitoring prescriptions
• Epidemiological studies
• Meta analyses
• Sociological studies

5
Representation of data on medicines safety,
obtained through clinical studies (370
randomized CS according to the data of the
Cochrane Library)
Bodil Als-Nielsen et. al. JAMA. 2003
6
Researching UR with regard to children and
pregnant women within CS
In the United States since 2002 the term of
validity of patents is extended for 6 months for
all the medicines, which were tested with the
participation of children, disregarding the fact
whether preparations were approved for
administering for children or not 107th
Congress of the United States of America. Best
pharmaceuticals for children Act, S.1789
109. Such support from the FDA and the
Government has resulted in a larger number of
studies with the participation of children within
the last 5 years, as compared to the number of
studies within the preceding 30 years in the
United States US Food and Drug Administration.
Drug research and children. FDA Consumer
Magazine, January-February, 2003.
66 of medicines were not researched within the
pregnant women for ethical reasons
LIST OF PERMITTED MEDICINES?
7
Number of patients required for identifying rare
unwanted reactions to medicines
8
Factors of clinical application of medicines

• Interaction with other medicines and food
  products
• Pharmacogenetical specific features of patients
• Unreasonable application of medicines
• Polypragmasy
• Errors of administration and application of
  medicines
• Counterfeiting medicines
• Therapeutic inefficiency
• Mistakes related to medicines names
• Significant period of applying medicines
• Unobvious dependence between UR and the medicine
  applied

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Pharmacoepidemiology of UR

• Incidence is from 4 to 40 of the patients who
  take medicines, and 2-3 of total population
• Shear N.H. et al., Drug Actions, Interactions,
  Reactions. 2000
• Serious complications are 6-7
• M. Dukes, 1998
• Lethality frequency is the 4th within ranking
• Shear N.H. et al., Drug Actions, Interactions,
  Reactions. 2000

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Frequency of unwanted reactions according to the
evaluation by specialists (?.?. Ovchinnikova)
11
Discrepancies of pharmacoepidemiological
evaluations of frequency of medicines unwanted
reactions
-Evaluation error? -Patients bias?
12
Untoward reactions either cause hospitalization,
or require prolongation of hospitalization period
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Mortality related to UR

• from the fourth to sixth rank within mortality of
  hospitalized patients
• Every year up to 140,000 people die of
  complications related to medicines therapy in the
  United States

Lazarou J. et al. JAMA, 1998
Porter J. et al. JAMA, 1997
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Expenditures related to the occurrence of UR
Expenditures for treatment of one
untoward reaction

• On the average,
• the occurrence of
• untoward reaction
• resulted in
• an increase of
• treatment cost
• by 2,262 US
• prolongation of
• hospitalization period
• by 1.91 days

Prolongation of in-patient treatment period for
patients having untoward reaction
Classen D.C. et al. JAMA, 1997
15
Financial expenses related to UR

• In the United States from 30 to 130 billions
  US per year
• Johnson JA, Bootman JL. Arch Intern Med
  19951551949-56
• In Switzerland - 70-100 millions CHF per year
• Fattinger K. et al., Br. J. Clin. Pharmacol.,
  2000
• cost 5.5-17 of total spending for healthcare
• Moore N.D. et al. Pharmacoepidemiology
• and Drug Safety, 1995
• In Russia these expenses could amount for 0.58
  to 1.8 billions US

16
Comparative willingness of pharmacists and
doctors to inform about medicines UR, according
to the survey (?.?. Ovchinnikova)
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Willingness of patients to inform about
medicines UR
18
Structure of pharmaco-therapeutic group of
medicines that caused UR, according to SS (1000
SS, ?.?. Ovchinikova, 2003)
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Structure of UR, by disorders of organs according
to the SS (1000 ??, ?.?. Ovchinnikova, 2003)
20
Composition of expenditures related to medicines
UR (1000 ??, ?.?. Ovchinnikova, 2003)
21
Reasons for serious UR related to medicines
(1000 ??, ?.?. Ovchinnikova, 2003)
Non- observance of the instruction of medical
application
22
Key failures to observe the instruction of
medical application (1000 ??, ?.?.
Ovchinnikova, 2003)

• Using inconsistent with indications set out in
  the IMP
• Repeated administration (UPR took place earlier)
• Under-evaluated anamnesis data
• Under-evaluated counter-indications
• Overdosing (absolute)
• Non-observance of dosing
• Unreasonable combination of medicines

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Out-patient practice experience

• UR are the only reason for 0.31 of total visits
  to polyclinics 2.73 millions of visits per year
  1.03 visits per 100 patients
• 88 of these patients visits result in stating
  temporary inability to work, the rest of cases
  require attending in-patient institution
• 76.3 millions of additional prescriptions per
  year are provided
• Aparasu R.R. et al., Manag Care Interface, 2000

24
Comparative data on UR based on the
epidemiological studies and studies obtained
through the prospective active monitoring within
the polyclinics in Moscow (K.E. Nazimkin, 2006)
Total 683 patients
25
Structure of UR in consistence with the medicine
that caused reaction
Active prospective monitoring medicines safety
within a polyclinics based in Moscow (K.E.
Nazimkin, 2006)
Total 683 patients
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Structure of UR in consistence with their type
Active prospective monitoring medicines safety
within a polyclinics (K.E. Nazimkin, 2006)
Total 683 patients
27
Survey of patients, doctors and pharmacists
(E.A. Ovchinnikova, 2006)
Have you ever seen that the names of medicines
were mixed?
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Survey of patients, doctors and pharmacists
(E.A. Ovchinnikova, 2006)
Is prescription required for a prescriptive
medicine?
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Relevance of evaluating UR for Russia

• Multiethnic country
• A large number of registered medicines
• Lack of a proper system of pharmacovigilance
• Lack of adequate methodology of UR of medicines
• Wide consumption of medicines that are unused
  abroad, i.e., impossibility of extrapolating the
  data from foreign countries to the national level
• Lack of large-scale monitoring studies

Unclear things should be clarified. Uneasy deed
should be done with outstandingly great
persistence. Confucius