Subject Recruitment and Retention: Barriers to Success in Clinical Trial

The Success to the Clinical trial depends upon the subject Recruitment and Retention but at the same time, successful recruitment of participants for any clinical trial is a challenge.

The Barriers to Recruitment and Retention may be classified in four broad groups: 

1.  Subject-Related Barriers.
2.  Investigator-Related Barriers.
3.  Protocol-Related Barriers.
4.  “Other” Barriers.

 Subject-Related Barriers :

1. Appointment hours are not Flexible.
2. Uncertainty towards the trial.
3. Unrealistic Expectation from the trial.
4. Disease Status.
5. Age of the patient.
6. Level of education.
7. Socioeconomic circumstances.

Investigator-Related Barriers:

1. Logistical Factors.
2. Personal Factors.

Protocol-Related Barriers:

1. Protocol designs with eligibility criteria that are so tight that potential study subjects do not be eligible for entry.
2. Protocols that is too difficult for investigators to follow due to overly Complex study designs.

Other Barriers :

Research studies that fail to meet recruitment goals provide minimal scientific return and may have a negative financial impact on the institution.

Low rates of recruitment and retention:-In order to increase the rate of recruitment and retention

1. Direct advertising should be encouraged.
2. Subject should be give the relevant information during the informed consent process.
3. Subjects rights should  be protected by ensuring the review of documents by IRB/IEC.
4. Develop an understanding of the population being recruited.
5. Provide the clear insight of the inclusion/exclusion criteria.
6. Develop close working atmosphere.

As the clinical trial is increasing the patient recruitment and retention is also becoming challenging.

1. Increased public alertness through campaigns would eliminate the recruitment and retention barriers created by geographic, socioeconomic, and cultural factors.
2. Individuals must be extra alert when dealing with the majority of subjects, who are ignorant, poor, and have a deep respect for and perhaps a blind belief in the physicians treating them.
3. Community education and consultation.

Importance of IT in Clinical Research Industry

The process of drug development and approval process takes a lot of time and is an expensive process. Generally, this process requires millions of dollars in investments and takes many years to complete.

  

Why the drug does takes more than 15 years to be launched into the market?

Since the drugs goes through different stages staring from lead discovery till marketing and each stages of drug discovery takes almost more than 2-3 year as a result of which the total years of drug discovery gets extended to approximately 10-12 years

Successful process takes

•     More than 10 years
•     More than $800 million – $1.2 billion
•     More than 10000 tested compound
•     For one drug

 Figure 1

Pharmaceutical and life sciences companies are outsourcing more of their activities to the IT Companies in a proposal to improve Research efficiencies and shorten the drug development timeline.

IT Players in Clinical Trial:-

• Accenture
• HCL
• Reliance
• Cognizant
• TCS
• Wipro
• Infosys 

Roles of the IT player:-

The IT Companies play major role in reducing the cost of the clinical trial by decreasing the timeline of approval process and increasing the efficiency of the trial by delivering accurate and reliable data. 
So, Pharmaceuticals companies are increasingly looking for partners to sustain them in their revolution, to optimize costs, and to bring innovation to the field of clinical research.
In what ways the IT Companies provides support to pharmaceutical industry?

1. By designing electronic capture instrument which facilitates the capture of massive amount of data generated during the conduct of clinical trial.
2. By designing and ensuring the testing (UAT)and validation of each and every process involved in design of the database.
3. Designing different dictionaries based on the requirement of client to enforce standardization as per the regulatory.
4. Provide support for data communication.
5. Provides confidentiality by ensuring security.
6. Furnish a mechanism to ensure that only authorized users can have access to the database.
7. Providing the opportunity to the Pharma companies to implement the existing standards and regulation.
8. For example, Title 21 Code of Federal Regulations under the FDA defines the guidelines for.
•   Electronic records.
•   System validations.
•   Processing of electronic data and signatures to demonstrate compliance with paper records.
9. By Offering real time web based reporting to client. 
10. By offering online reporting system to enhance and fasten the reporting of any SAE appearing once the drug is being marketed.
11. By bringing efficiency to its US sales and marketing operation, through a range of solutions spanning commercial analytics, sales force planning, sales incentive compensation, customer relationship.
12. Furnish a mechanism for recovering the database if the database is damaged in any ways.

     

Conclusion:-

 The data management processing not only improves the overall cost of the clinical trial but also enhances the sharing and integrity of the clinical data .Henceforth reducing the redundancy.

Targeted delivery system is a niche scientific development, but is there an established delivery mechanism to handle it?

An absolutely novel way of anti-tumor drug delivery for the first time in human using “minicells” derived from bacteria is found to be safe, well tolerated and effective even in advanced stages of cancer. A biotech company in Sydney, Australia, designed the minicells created from small bubbles of cell membrane pinched off the surface of mutant bacteria[1]. These minicells, help to deliver anti-cancer drugs directly to tumor cells, thereby reducing the toxic side-effects that are seen when chemotherapy is given to patients systemically.

In chemotherapy,there are many toxic side effects like Fatigue,Skin Problems,Hair Loss,Loss of appetite, Lymphodema, Vertigo, Urinary tract infections,Hemorrhagiccystitis,hairloss (alopecia) etc..,, Hair loss is one of the most distressing side effect of cancer treatments. Hair loss happens because the chemotherapy affects many other cells in the body, not just the cancer cells. The lining of the mouth, stomach, and the hair follicles are especially sensitive because those cells multiply rapidly just like the cancer cells[2]. 

The chemotherapy drugs are transported through the blood and eventually access the cancer cells. The problem with chemotherapy drugs is that when they attack cancer cells, they can also attack the healthy cells. In most cases, the healthy cells can survive, but sometimes the attack on the healthy cells results in side effects[3]. Minicells acts only on the affected cancer cells because of special form of drug delivery system where pharmacologically active agent is selectively targeted only to the site of action and not to the non-targeted site which then minimizes the side effects caused due to chemotherapy.

The difference is that the normal cells will repair themselves, making these side effects temporary. Minicells acts only on the targeted cells without affecting the normal cells thus minimizing the side effects caused due to the chemotherapy which desperately damages the normal cells. Targeted drug delivery system is a felicitous method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others where only the affected cancer cells gets cured. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue[4].

Minicells are generally filled with anti-tumor drugs and encrusted with antibodies targeting the encumbered minicells to tumors expressing the Epidermal Growth Factor Receptor (EGFR) a protein that is found on the surface of many cancer cells. Minicells acts as the targeted release system helps in reducing the frequency of the dosages taken by the patient, having a more uniform effect of the drug, minimizes side effects of drug, and also helps in reducing fluctuation in circulating drug levels. This shows that the minicells reach the tumor cells averting normal cells which obviously don’t have the same receptors.

The tumor cell determines the bacteria from which this minicell has being derived and activates its defense by swallowing the minicell, which manifests cell nucleus to whichever tumor-killing drug the minicell is carrying [5].Each minicell is 200 times smaller in diameter than a human hair. This is the very promising and advanced treatment for cancer where there is a selective delivery of anti tumor drug at the targeted site which safeguards the normal cells from needless adverse effects.

In the future this will enable a truly tailored medicine approach to cancer treatment, as the million molecules of the drug can be attached to the targeting antibodies and delivered to the body in a secure manner[6]. Targeting of drugs to special cells and tissues of the body without their becoming a part of systemic circulation is a very novel idea. But there are no proper methods to administer into the human body.

Delivery mechanism of minicells is a desired pharmacological response at the selected sites without undesirable interaction at other sites; there by the drug have a specific action with minimum side effects and better therapeutic index[7]. But it is very expensive method and the main drawback is that the minicells will not get absorbed in the gastrointestinal tract when administered orally, moreover there is no much information regarding route of administration of minicells and how they act exactly. 

Although it is very effective in vitro, there is no established mechanism to deliver minicells in vivo. By which route these minicells are administered is not known properly and it is still remained a question, as how to deliver this minicells in best effective manner.

Reference:

• http://chemocare.com/chemotherapy/side-effects/default.aspx 
• http://www.inblackandwhitecopy.com/samples/chemo-side-effects.pdf
• Muller, R; Keck, C (2004). "Challenges and solutions for the delivery of biotech drugs – a review of drug nanocrystal technology and lipid nanoparticles". Journal of Biotechnology 
• http://www.medindia.net/news/first-trial-of-delivering-anti-cancer-drugs-in-humans-109842
• http://www.ecco-org.eu/Global/News/ENA-2012-PR/2012/11/9_11-First-trial-in-humans-of-minicells.aspx