Health Reg + Research

Universities for Allied Medicines

posted 16 Jun 2012, 13:58 by NicolaAvery

Global Access Licensing Framework (access to essential medicines - university development)

  • Generic production - 
  • “at-cost” or other provisioning requirements should be used as a supplement to generic provisioning 
  • non-exclusive licensing (compared to traditional terms / years etc)
  • products that are originally licensed for lifestyle indications should have global access provisions in their license - when non-lifestyle indications - researched / peer reviewed
  • The financial impact to pharmaceutical companies of allowing generic competition in resource-limited countries is negligible, especially when the global access license offers licensees revenues from reasonable royalties on the generics
  • excessive waiting time for reference to clinical trials for bioequivalent drugs
  • at cost - when drug/research/production too complex or demand too small
  • publication of redacted licences
  • metrics for strategies of implementation of licences and frequency of implementation

Tips for understanding studies

posted 2 Jun 2012, 00:44 by NicolaAvery via

"A surrogate marker is an event or a laboratory value that researchers hope can serve as a reliable substitute for an actual disease. A common example of this is blood cholesterol levels. These levels are surrogates, or substitutes, for heart disease. If a medical study demonstrates that a medication can lower cholesterol level 10%, then we assume that this will also lower the risk of cardiovascular disease. Why doesn’t this same study determine if an anti-cholesterol drug decreases heart attack rates directly? After all, most folks would rather be spared a heart attack than have a silent decrease in their blood cholesterol levels. It is much easier and cheaper for researchers to measure surrogates than actual disease events"


Clinical Trial Core Components

posted 21 May 2012, 13:37 by NicolaAvery   [ updated 10 Jun 2012, 12:12 ]

Observational Studies: Groups are studied & contrasts made between groups. The observed data collected are analyzed
Analytic Studies: Also called Experimental. Study the impact of a certain therapy. Ultimately the investigator controls factor being studied
Clinical Trial: Considered the “true” experimental study. “Gold Standard” of clinical research. Often a prospective study that compares the effect and value of an intervention against a control in human subject.

 Types of Research Study
 Types of Clinical Trial
  • Retrospective: Refers to time of data collection
  • Prospective: Refers to time of data collection
  • Case Control Study: Persons w/ disease & those w/out are compared
  • Cohort Study: Persons w/ and/or w/out disease are followed over time
  • Cross-sectional Study: Presence or absence of exposure to possible risk factor measured at one point in time. Prevalence obtained.
  • Prevalence: The # of new cases and existing cases during specified time period.
  • Incidence:  The # of NEW cases per unit of a population at risk for disease occurring during stated time period.

  • Randomized/blinded trial
  • Randomized/double blinded trial
  • Non-randomized concurrent controlled trial
  • Placebo trial
  • Historical controlled trial
  • Crossover Trial
  • Withdrawal trial
 Designing an Experiment*  Designing a Clinical Trial*
Test a hypothesis
Change one factor at a time (the independent variable)
Observe outcomes (the dependent variables)
Compare effect of two different antibiotics on bacterial growth rate
Independent variable:  type of antibiotic
Dependent variable: growth rate of bacteria
Must ensure that every variable (e.g. temperature, concentration of antibiotic, duration of experiment) remains the same except for choice of antibiotic
Compare effectiveness of two different medical procedures
Two groups of patients, each receives a different medical procedure (independent variable)
Observe clinical outcomes in the groups of patients (dependent variables)
Primary outcome:  Most clinically important outcome
Secondary outcomes: Other clinical results of interest
Compare effectiveness of two different types of antibiotics to treat bacterial pneumonia
Independent variable: Type of antibiotic
Dependent variables:
Primary outcome: duration of symptoms
Secondary outcomes: severity of symptoms
Must ensure that every variable (e.g. ages of patients, concentration of antibiotic, severity of initial disease) remains the same except for the choice of antibiotic
* via


  • Involve human subjects
  • Move forward in time
  • Most have a comparison CONTROL group
  • Must have method to measure intervention
  • Focus on unknowns: effect of medication
  • Must be done before medication is part of standard of care
  • Conducted early in the development of therapies
  • Must review existing scientific data & build on that knowledge
  • Test a certain hypothesis
  • Study protocol must be built on sound & ethical science
  • Control for any potential biases
  • Most study medications, procedures, and/or other interventions

Computational method predicts new uses for existing medicines (NIH)

posted 19 May 2012, 12:32 by NicolaAvery

"The scientists drew their data from the NIH National Center for Biotechnology Information Gene Expression Omnibus, a publicly available database that contains the results of thousands of genomic studies on a wide range of topics, submitted by researchers across the globe. The resource catalogs changes in gene activity under various conditions, such as in diseased tissues or in response to medications.

Butte’s group focused on 100 diseases and 164 drugs. They created a computer program to search through the thousands of possible drug-disease combinations to find drugs and diseases whose gene expression patterns essentially cancelled each other out. For example, if a disease increased the activity of certain genes, the program tried to match it with one or more drugs that decreased the activity of those genes."

  • An anti-ulcer medicine - cimetidine, which matched with lung cancer - tested on human lung cancerous cells in dishes, slowed the growth of cancer cells
  • An anticonvulsant - topiramate - matched with inflammatory bowel disease (incl Crohns), in rats decreased symptoms, better than prednisolone

"The scientists noticed that diseases with similar molecular processes (for example, those that affect the immune system) clustered together in the analysis. So did drugs with similar effects (for example, those that slow cell division). The researchers believe that, by studying unexpected members of these clusters, they could learn more about how certain diseases progress and how some drugs work at the molecular level."

Medical Regulatory History

posted 9 Apr 2012, 11:19 by NicolaAvery   [ updated 20 May 2012, 02:19 ]

Pharmacopoeias appearing from 16th century onwards


"There were over 50 legislative attempts to address aspects of medical regulation between 1840 and 1886, with the Medical Act of 1858 establishing the General Medical
Council (GMC). The GMC has four main statutory functions: setting standards for good medical practice; assurance of the content and quality of basic medical education; running the registration and licensing system for doctors; and handling complaints and concerns about doctors’ fitness to practise."

MHRA established 2003 (Medicines Control Agency + Medical Devices Agency), medical regulation more formalised after Thalidomide experimentation 1950s/60s, Committee on Safety of Drugs 1963, then Medicines Act 1968 - Commmittee on Safety of Medicines, then 2005 - Commission on Health Medicines. Medicines Act required medicines to be licensed before being introduced to UK Market. Since then superseded by European legislation

EEC 65/65 Council Directive to regulate post thalidomide - similar to Medicines Act. Since then 1975 - 75/318/EEC - "analytical, pharmacotoxicological and clinical standards
and protocols in respect of the testing of proprietary medicinal products" and 75/319/EEC - "law, regulation and administrative action relating to medicinal products" introducing mutual recognition procedure, then 87/22/EEC - centralized procedure. EMA established 1993

US The Evolution of Public Health Regulation, Eleanor D. Kinney Bioterrorism, Public Health and the Law, Law 801: Health Care Law Seminar Professor Vernellia R. Randall

In US, focus on local public health agency for public health issues, initially 1793 Baltimore, then across US in early 19th century. Then moved to states as more was understood about infectious diseases and the spread. Federal Public Health Regulation - three phases
  • when specific health threats not adequately addressed at local, state levels including Marine Health Service = National Public Health Service in 1912and food and drug safety regulation - food,drug and cosmetic act 1906 which led to FDA
  • New Deal - establishment of FDA and improved food, drug and cosmetic act 1938 - demonstrated safety of new drugs required, 1930 Ransdell Act - establishment of National Institutes of Health then post WWII - Centers for Disease Control, including Medicare and Medicaid programs, 1979 education & health combined into department of Health and Human Services
  • workplace health and safety - Occupational Health & Safety Act 1970, established Occupational Health and Safety Administration
"One important issue regarding risk is the irrationality of perceptions of risk, particularly when the risk has attracted media and public concern. Often, in that event, the atmosphere in which agency decisions are made responding to the risk is politically charged and even emotional. Many have argued that public knowledge and pressure disproportionately influence policymakers. Others maintain that interest groups have too much influence in driving the agenda of risks to be addressed and the factors to be considered in their assessment.

Risk assessment is especially important to public health agencies. Almost all public health regulation is about risk to health and safety. Specifically, much of public health regulation addresses ways to reduce risks to health and safety in the environment, workplace, and other settings. Also, much of public health practice involves educating the public about the risks of various practices and habits. Through sound risk assessment, a public health agency can make more accurate determinations of what are the most serious risks on which to focus regulatory attention. A good scientific understanding of the nature of the risk should suggest regulatory techniques that will be the most effective in addressing the risk at a reasonable cost. Public health agencies, in particular, need good data on which to base risk assessment."

Other International (supported by WHO)

"establishment in 1990 of the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH), a collaborative initiative between the EU, Japan and the United States with observers from WHO, EFTA and Canada. ICH harmonization focuses primarily on technical requirements for new, innovative medicines. However, countries with limited resources are mostly generic markets and may have difficulties of implementing numerous sophisticated ICH standards. Pharmaceutical regulatory harmonization facilitates the availability of safe, effective and good quality pharmaceuticals",

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