How Do You Get Your Product Fit for Marketing?
What can go wrong? (30 min)
Each phase of development can have problems or fail completely and starting over again.
Research and Pre Clinical
Animal models or simulations which do not translate or not entirely related to human disease1
Evidence from other pre-clinical studies is insufficient or negative data from other clinical trials is not published in enough detail 2
Identification of appropriate biological targets
Regular access to labs and equipment access are unknown or unreliable
Chemicals and biologics become unstable in different environmental conditions (WHO Technical report, Chinese Traditional Medicine study).
Clinical Phase 1
Unable to recruit trial participants e.g. your target group may not be able to participate due to other drugs or therapies they are receiving
Inappropriate dose selection for next phases (inadequate analysis of pharmacokinetics and pharmacodynamics [ EUPATI PD & PK ] 3
Study design and protocols leads to poor clinical practices4
Clinical Phase 2
Molecular entities do not behave as predicted5
Insufficient or incorrect data collection and analysis leading to assumptions, bias in results interpretation including sampling and statistical errors 6
Lack of efficacy in therapeutic area (e.g. unable to meet cardiovascular or oncology endpoints such as changing / shrinking tumour or disease progression)7
Inadequate documentation or specification of procedures causes manufacturing errors producing adverse clinical results
Clinical Phase 3
Unexpected adverse or serious adverse events such as injury, illness or death8
Unable to demonstrate value compared to existing therapy (e.g. in an HTA)9
Trial design causes a trial to take longer than expected resulting in funding and infrastructure problems (grants for specific activity/ timescale, clinical environments and equipment available for limited time)
Post Marketing Approval
Patients do not read or understand the safety information provided with a drug or device or other pharmacovigilance signals show unpredicted adverse or serious adverse events8 leading to recall of medicines, devices or approval being revoked.
Consistency with multiple manufacturing sites e.g.causing public health issues through inadequate pharmaceutical waste disposal
Supply chain becomes unreliable resulted in manufacturing being suspended and loss of revenue.
Limited scientific knowledge of patients or specified sales targets for pharmacists results in unfair representation of e.g. a generic medicine compared to a brand.
Case Studies
1. Stanley A (2016), pp24-7, Preventing Phase 3 failures, Vol 1 Supplement, Pharmaceutical Technology
2. Failures in Phase 3 Causes and Consequences Clinical Cancer Research Journal, DOI: 10.1158/1078-0432.CCR-15-0124, Retzios A (2009) Why do so many Phase 3 clinical trials fail? Bay Clinical R&D
3. Grignolo A, Pretorius S (2016) Phase 3 Trial Failures: Costly but Preventable, Applied Clinical Trials 25:8
4. Grignolo A, Pretorius S (2016) Phase 3 Trial Failures: Costly but Preventable, Applied Clinical Trials 25:8
5. Grignolo A, Pretorius S (2016) Phase 3 Trial Failures: Costly but Preventable, Applied Clinical Trials 25:8
6. Grignolo A, Pretorius S (2016) Phase 3 Trial Failures: Costly but Preventable, Applied Clinical Trials 25:8, Retzios A (2009) Why do so many Phase 3 clinical trials fail? Bay Clinical R&D
7. Failures in Phase 3 Causes and Consequences Clinical Cancer Research Journal, DOI: 10.1158/1078-0432.CCR-15-0124, Retzios A (2009) Why do so many Phase 3 clinical trials fail? Bay Clinical R&D
8. Failures in Phase 3 Causes and Consequences Clinical Cancer Research Journal, DOI: 10.1158/1078-0432.CCR-15-0124
9. Grignolo A, Pretorius S (2016) Phase 3 Trial Failures: Costly but Preventable, Applied Clinical Trials 25:8
Phase 2 and Phase 3 failures 2013-15 Harrison, Richard K, Nature Reviews Drug Discovery, 15, 817–818
Clinical Pharmacokinetics and Phamacodynamics - concepts and applications 4th edn, Rowland M, Tozer T, 2009, Philadelphia : Lippincott William & Wilkins, available via http://www.worldcat.org/title/pharmacokinetics-and-pharmacodynamics-concepts-and-clinical-applications/oclc/524363543