3 Signs of poorly designed clinical trial protocol [Includes research protocol checklist]

3 Signs of poorly designed clinical trial protocol [Includes research protocol checklist]

  The foundation of every clinical trial is a clinical protocol. It is an important document that describes in detail all the crucial elements of the research. In fact, having a clear and well-designed clinical trial protocol is essential before the initiation of a clinical trial. Some of the purposes the protocol serves are:

  • It guides the principal investigator by providing him/her an official record of the procedure that needs to be followed during the clinical trial1.
  • It apprises the study participants of the exhaustive illustration of the trial procedures and methodology2.
  • It informs the independent ethics committee/institutional review board that the study conforms to the ethical standards for clinical research1.
  • It helps the sponsors who are investing in the study to estimate the overall effort required for the trial and foresee if the trial is feasible5.

As the protocol is essentially the roadmap for everyone involved in the study, it should be written succinctly and clearly. Despite the requirements for a well-designed protocol, many of the protocols that we come across are poorly designed. This is because many authors find it challenging to write the protocol. In this article, I will discuss the common mistakes that authors make when writing protocols. They are listed below:       

1. Unclear specification of the sponsor and investigator responsibility

A clear outlining of the sponsor and investigator responsibilities is one of the basic requirements of clinical trial protocols. However, it is commonly observed that many protocols fail to do this3. If the sponsor and investigator responsibilities are not meticulously outlined, there may be delays in initiating the study and conducting the trial. Investigators oversee the regulation of proper handling, stockpiling, and obliterating of the new drug under study4.

Similarly, sponsors oversee quality control to ensure that the trial is conducted and data is generated according to the protocol5. If the protocol lacks clear specification of the sponsor and investigator responsibility, the resulting protocol will not ensure proper and safe use of the new drug during the trial.

2. Lack of methodological details

Methodology forms a crucial part of the protocol. One of the indicators of a poorly designed protocol is the lack of methodological details, such as missing out on reporting the primary outcomes and power calculations that determine the test’s statistical significance6,7.

Hence the content of clinical trial protocol should include methodological insights regarding test size, while the full investigation ought to be reported in the trial. It is only with a clear reporting of the methodological details that the study can be considered reliable and safe.

3. Unclear allocation concealment

A poorly designed trial can be potentially misleading and lead to biases in the study8. Randomization is, therefore, done with the intent to prevent bias from creeping in by distributing subjects into two study arms without any knowledge of their medical condition8. This means the medical condition of the subjects needs to be concealed from the person who oversees the allocation.

Many protocols do not provide sufficient details about the allocation concealments. Hence to make the trial reliable its protocol should ensure that details about allocation concealments are clearly provided.

Clinical trials are vital to testing the efficacy and safety of new treatment methods. Therefore, chalking out a detailed protocol is of extreme importance. Admittedly, this can be a complex and long drawn process, but avoiding the above-mentioned mistakes while developing the trial protocol will help in enhancing the reliability of a clinical trial results for a new drug or treatment method. 

Research Protocol Checklist

  1. Background and rationale - the main reasons for conducting the clinical trial
  2. Objectives - the critical questions the research study addresses
  3. Informed consent - the consent from participants
  4. Subject selection criteria - inclusion and exclusion criteria
  5. Treatment plan and study procedures - research method 
  6. Statistical analysis plan - how data and information will be processed
  7. Assessment of safety and efficacy - listing of any risks
  8. Anticipated results and study limitations   

(Reference: A young researcher's guide to a clinical trial)

 

Related reading:

 

References:

  1. ICH guidelines http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Step_4_2016_1109.pdf
  2. Kane JL, Wang J, Garrard J (2007) Reporting in randomised clinical trials improved after adoption of the CONSORT statement. J Clin Epidemiol 60: 241–249.
  3. Gøtzsche P, Hrøbjartsson A, Johansen H, Haahr M, Altman D, Chan A: Ghost authorship in industry-initiated randomised trials. PLoS Med 2007, 4:e19.doi:10.1371/journal.pmed.0040019.
  4. Allison R. Baer, RN, BSN, Susan Devine, CCRP, Chris David Beardmore, and Robert Catalano, PharmD: Clinical Investigator Responsibilities. J Oncol Pract. 2011 Mar; 7(2): 124–128.
  5. ICH guidelines for sponsors, http://ichgcp.net/5-sponsor
  6. Chan AW, Hróbjartsson A, Haahr MT, Gøtzsche PC, Altman DG: Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA. 2004, 291: 2457-2465.
  7. Chan AW, Hróbjartsson A, Jørgensen KJ, Gøtzsche PC, Altman DG: Discrepancies in sample size calculations and data analyses reported inrandomised trials: comparison of publications with protocols. BMJ 2008, 337:a2299.
  8. Pildal J, Chan AW, Hróbjartsson A, Forfang E, Altman DG, Gøtzsche PC: Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study. BMJ 2005, 330:1049.

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