Clinical Trials And The Phases

 

Hello, readers this is my first blog on clinical trials and the phases. As an introduction, I have done graduation in biotechnology and now I am pursuing post-graduation in Statistics at S.K Somaiya College. The transition from life science stream to statistics is not easy nor it is difficult, it’s all about extra efforts from your end. You have to have basic knowledge of statistics like for example measures of central tendency a.k.a mean standard deviation and various other parameters and mathematics for example basics of distributions, differentiations, integrations, combinatorics (added value is that it will also help in quantitative aptitude test to some extend).

The core inspiration to transit my career was first application of data science in statistics then it evolved into working with clinical trial data analysts’ team.

Moving on to clinical trials topic.

        Clinical trial is a process in which a drug/vaccine/ diagnostic test is tested on               human subjects to understand the effect, safety and efficacy of that product.

    PHASES

    I had put a summarized table at the end of this paragraph. Going in a little bit detail        in each of the phase.
    
    

 

Phase Zero:    

 We are talking about preclinical phase. Imagine a lab which had found 1,00,000 compounds in which there are chances that a certain compound in those many compounds have a capability to be more effective or effective antibiotic to treat certain illness in humans. If  my reader belong or had develop career in biomedical or life sciences field, then as an outline you know after getting those compounds certain tests are performed on human cells and animal models.
Out of which very few compounds are selected based on certain criteria, which can be tested in clinical phase a.k.a clinical trials on human subjects.

Some keywords which I recommend to explore more about them: 
Therapeutic index, toxic effect, pharmacodynamics, pharmacokinetics, biochemical tests.
                                                                    

Phase One:

After in preclinical phase a document "Investigational New Drug" application is submitted to FDA for approval to allow organization to conduct clinical trials. In this application all the information generated on the product is documented according to SOPs and the statistical plan, procedure and how many healthy/ immunocompromised/ diseased patients are needed in clinical trial phases. If FDA approves, then Phase I  of clinical trial is conducted. The data generated over the next two phases is analyzed while trial is going on. The analysis is submitted to the authorities to decide whether to move forward to next phase of clinical trial or to terminate it.

• 20-100 subjects (healthy and diseased) are needed
• Dosing schemes are designed and accordingly drug and placebo are given to subjects.

Some keywords:

Therapeutic index, toxic effect, maximum tolerated dose, single ascending dose, multiple ascending dose and many more go ahead and explore more about these terms!

Phase Two:

During this phase a more number of volunteered participants are involved in the clinical trial. This phase aims to record the safety and efficacy of investigational product on human subjects. There are two subparts to this phase IIA and IIB; the former consist of single blind and the latter consist of double blind with standard or placebo group in it.

Phase Three:

After phase two in phase three a large number of volunteered participants are involved in this clinical trial. It is conducted to test the efficacy and monitor adverse and severe adverse reactions of this product on human subjects. There are two subparts to this phase:

IIIA and IIIB; in this IIIA phase data is generated and analysis and all the documents are again submitted to FDA for continuing of the clinical trial but this time the document is named as "New Investigational Product". Once it gets approved to continue the trial the latter phase IIIB is conducted across many different sites (hospitals).

Data generated is stored and locked in a certain database. ECRF/Electronic Case Report forms are filled and data is extracted from those forms and cleaned and stored in database which is basically read for statistical analysis.

Phase Four:

After interacting with biostatisticians, authorities and detailed discussion this phase is conducted to reconfirm the efficacy and safety of drug and to know more about side effects of that product. Further, in this phase many comprehensive studies are performed. 

Finally after all the analysis and thorough investigation and approval from FDA the new investigational product is manufactured according to standard operating procedures and is brought into the market.

The timeline of the whole clinical phase is around 6-12 years.

SUMMARY TABLE:

Phases	Purpose/key points
ZERO	PRECLINICAL LEVEL: “DRUG/COMPOUND IS TESTED ON LAB ANIMALS”
ONE	“DOSING SCHEMES ARE DESIGNED AND THEIR EFFECT IS SEEN ON HEALTHY AS WELL AS DISEASED HUMANS (DRUG WHICH CLAIMS TO TREAT THAT PARTICULAR DISEASE)”
TWO	“EFFICACY MEANS WHETHER THE DRUG IS SHOWING EXPECTED RESULTS OR NOT IN HUMAN SUBJECT WHICH IT SHOWN AT LAB LEVEL AND REPORTING ADVERSE AND SEVERE ADVERSE REACTIONS OF DRUG ON HUMAN SUBJECTS”
THREE	“AGAIN, EFFICACY AND MONITORING ADVERSE AND SEVERE ADVERSE EVENTS”
FOUR	“STATISTICAN'S VALIDATION AND AGAIN PERFORMED TO RECORD SAFETY AND EFFICACY OF DRUG FOR COMPHRENSIVE ANALYSIS”

        



A note to all:

The above information that I have written in this blog about phases their purpose may vary in clinical trials as well as in different reference books. Hopeful, you may found this blog informative and creative well enough!

In the upcoming blog I will post on the clinical data management and good clinical practice.