PMC:7784828 / 8489-14239 JSONTXT

{"project":"LitCovid-PD-HP","denotations":[{"id":"T14","span":{"begin":5285,"end":5289},"obj":"Phenotype"},{"id":"T15","span":{"begin":5524,"end":5534},"obj":"Phenotype"}],"attributes":[{"id":"A14","pred":"hp_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/HP_0012531"},{"id":"A15","pred":"hp_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/HP_0000716"}],"text":"3. Challenges facing the current drug development process\nThe lack of ample effective and affordable medicines is one of the vexing challenges faced globally. It is imperative to generate novel treatment strategies, however, fair pricing and quick access to medicines remain a massive global challenge. Chronic shortages and rising demands for critical drugs affect patient community with many dying from easily curable diseases [24]. To a large extent, present day drug development and discovery is controlled oftentimes by private entities which are driven by vested economic interests and boundary conditions. This leads to the burden trickling down to patients, their families and carers either through lack of effective medicines or mounting financial costs. Addressing these global issues is the need of the hour and a plausible solution could be devising new tools and technologies, novel methodological approaches, and infrastructural changes to streamline the drug discovery review processes. On the other hand, the desperate need for new effective drugs raises a concern over the efficacy of many of the currently marketed drugs. A study examining efficacy of solid tumors therapies approved by the FDA between 2002 and 2014, found only 30 out of 71 therapies (42%) to have modest clinically meaningful improvements [25]. Sluggish data sharing and irreproducibility of published research remains as another major challenge. A 2016 survey of 1,576 researchers by the journal Nature found that over 70% of researchers have failed to reproduce other scientist’s experiments [26].\nThe challenges in drug discovery and development for academics, research communities, and pharma industries needed for successful drug development can be broken down to cost, risk as well as pace.\n\n3.1. Cost and risk\nThe amount spent to develop an individual drug largely depends on the costs to conduct safety and efficacy studies and also to secure regulatory approvals. Estimates for the cost for Drug development range from ~ 1 billion to whopping 11.8 billion for a single drug [27,28]. However, around 90% of drugs in development for human use do not reach the market due to safety or efficacy concerns. Such failures can be due to lack of efficacy, safety issues, or a lack of funding to complete a trial [29]. In other cases, failing to maintain good manufacturing protocols and follow FDA guidance, as well as problems with patient recruitment, enrollment, retention and follow up can all compound to both complicate and increase the cost needed for drug development [29]. Given this mounting cost with little success due to high attrition rates, it is obvious that the drug development as a business model is very risky purely from an economical and financial sense. Aside from the high cost/high attrition rates nature of the drug discovery process, other drugs, like antibiotics or orphan drugs, are often abandoned and don’t reach the market due to little or no commercial interest [30].\n\n3.2. Pace\nThe process of drug research and development is extremely slow taking at least 7 to 10 years for a lead candidate to reach the marketplace [28]. This is mainly due to the rigorous process needed to ensure safety and efficacy through clinical human trial and as well as obtaining regulatory approvals. Duplication and reproducibility are other factors that also contributes to the slow pace of drug discovery. While duplication and reproducibility can be seen as a squander of time and resources, they remain essential to provide more data and evidence and ensure the safety and efficiency before they are prescribed to the population. The devastating malformations of children born to women prescribed ‘Thalidomide’, to treat morning sickness is a stark reminder of the important of independent rigorous evaluation of a drug’s safety profile before its release for population [31]. A more recent example, hydroxychloroquine as a treatment for COVID-19, highlights the importance of multiple and independent studies needed to demonstrate a drug’s safety and efficiency [32]. Other factors include, suboptimal collaboration or lack of meaningful collaborative efforts among academia, industry, and government institutions despite several effort to encourage collaboration [33]. This have led, on many instances, to academics and pharma sectors working on similar ideas in parallel, in secret, and often in competition. Therefore, the establishment of a trusted and fair framework of collaboration and data sharing can both speed up the pace and improve the outcome of successful drugs.\n\n3.2. Limitations and more of the same\nA large number of drugs approved by the FDA in the past 10 years are new formulations of existing drugs referred to as ‘me too drugs’. While in some cases these drugs have offered some improvements over older versions, in many cases improvements remain marginal with slight changes in side effects or activity profiles [34]. Since these drugs have identical mechanism of action to older versions their innovative value and overall benefit is oftentimes insignificant [35]. Additionally, the molecular effects of several marketed drugs remain unknown despite their proven effectiveness. For example, acetaminophen is used by millions to treat mild to moderate pain while lithium is a first-line treatment for biopolar disorder. Yet the exact molecular target and mechanism of action remain unknown [36,37]. Many diseases particularly those affect the nervous system like Alzheimer, Parkinson’s, and depression lack accurate biomarkers [38,39]. While progress is being made, the lack of reliable biomarkers remains another impediment for the accurate diagnosis, prognosis and effective drug development against these diseases."}

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Challenges facing the current drug development process\nThe lack of ample effective and affordable medicines is one of the vexing challenges faced globally. It is imperative to generate novel treatment strategies, however, fair pricing and quick access to medicines remain a massive global challenge. Chronic shortages and rising demands for critical drugs affect patient community with many dying from easily curable diseases [24]. To a large extent, present day drug development and discovery is controlled oftentimes by private entities which are driven by vested economic interests and boundary conditions. This leads to the burden trickling down to patients, their families and carers either through lack of effective medicines or mounting financial costs. Addressing these global issues is the need of the hour and a plausible solution could be devising new tools and technologies, novel methodological approaches, and infrastructural changes to streamline the drug discovery review processes. On the other hand, the desperate need for new effective drugs raises a concern over the efficacy of many of the currently marketed drugs. A study examining efficacy of solid tumors therapies approved by the FDA between 2002 and 2014, found only 30 out of 71 therapies (42%) to have modest clinically meaningful improvements [25]. Sluggish data sharing and irreproducibility of published research remains as another major challenge. A 2016 survey of 1,576 researchers by the journal Nature found that over 70% of researchers have failed to reproduce other scientist’s experiments [26].\nThe challenges in drug discovery and development for academics, research communities, and pharma industries needed for successful drug development can be broken down to cost, risk as well as pace.\n\n3.1. Cost and risk\nThe amount spent to develop an individual drug largely depends on the costs to conduct safety and efficacy studies and also to secure regulatory approvals. Estimates for the cost for Drug development range from ~ 1 billion to whopping 11.8 billion for a single drug [27,28]. However, around 90% of drugs in development for human use do not reach the market due to safety or efficacy concerns. Such failures can be due to lack of efficacy, safety issues, or a lack of funding to complete a trial [29]. In other cases, failing to maintain good manufacturing protocols and follow FDA guidance, as well as problems with patient recruitment, enrollment, retention and follow up can all compound to both complicate and increase the cost needed for drug development [29]. Given this mounting cost with little success due to high attrition rates, it is obvious that the drug development as a business model is very risky purely from an economical and financial sense. Aside from the high cost/high attrition rates nature of the drug discovery process, other drugs, like antibiotics or orphan drugs, are often abandoned and don’t reach the market due to little or no commercial interest [30].\n\n3.2. Pace\nThe process of drug research and development is extremely slow taking at least 7 to 10 years for a lead candidate to reach the marketplace [28]. This is mainly due to the rigorous process needed to ensure safety and efficacy through clinical human trial and as well as obtaining regulatory approvals. Duplication and reproducibility are other factors that also contributes to the slow pace of drug discovery. While duplication and reproducibility can be seen as a squander of time and resources, they remain essential to provide more data and evidence and ensure the safety and efficiency before they are prescribed to the population. The devastating malformations of children born to women prescribed ‘Thalidomide’, to treat morning sickness is a stark reminder of the important of independent rigorous evaluation of a drug’s safety profile before its release for population [31]. A more recent example, hydroxychloroquine as a treatment for COVID-19, highlights the importance of multiple and independent studies needed to demonstrate a drug’s safety and efficiency [32]. Other factors include, suboptimal collaboration or lack of meaningful collaborative efforts among academia, industry, and government institutions despite several effort to encourage collaboration [33]. This have led, on many instances, to academics and pharma sectors working on similar ideas in parallel, in secret, and often in competition. Therefore, the establishment of a trusted and fair framework of collaboration and data sharing can both speed up the pace and improve the outcome of successful drugs.\n\n3.2. Limitations and more of the same\nA large number of drugs approved by the FDA in the past 10 years are new formulations of existing drugs referred to as ‘me too drugs’. While in some cases these drugs have offered some improvements over older versions, in many cases improvements remain marginal with slight changes in side effects or activity profiles [34]. Since these drugs have identical mechanism of action to older versions their innovative value and overall benefit is oftentimes insignificant [35]. Additionally, the molecular effects of several marketed drugs remain unknown despite their proven effectiveness. For example, acetaminophen is used by millions to treat mild to moderate pain while lithium is a first-line treatment for biopolar disorder. Yet the exact molecular target and mechanism of action remain unknown [36,37]. Many diseases particularly those affect the nervous system like Alzheimer, Parkinson’s, and depression lack accurate biomarkers [38,39]. While progress is being made, the lack of reliable biomarkers remains another impediment for the accurate diagnosis, prognosis and effective drug development against these diseases."}

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Challenges facing the current drug development process\nThe lack of ample effective and affordable medicines is one of the vexing challenges faced globally. It is imperative to generate novel treatment strategies, however, fair pricing and quick access to medicines remain a massive global challenge. Chronic shortages and rising demands for critical drugs affect patient community with many dying from easily curable diseases [24]. To a large extent, present day drug development and discovery is controlled oftentimes by private entities which are driven by vested economic interests and boundary conditions. This leads to the burden trickling down to patients, their families and carers either through lack of effective medicines or mounting financial costs. Addressing these global issues is the need of the hour and a plausible solution could be devising new tools and technologies, novel methodological approaches, and infrastructural changes to streamline the drug discovery review processes. On the other hand, the desperate need for new effective drugs raises a concern over the efficacy of many of the currently marketed drugs. A study examining efficacy of solid tumors therapies approved by the FDA between 2002 and 2014, found only 30 out of 71 therapies (42%) to have modest clinically meaningful improvements [25]. Sluggish data sharing and irreproducibility of published research remains as another major challenge. A 2016 survey of 1,576 researchers by the journal Nature found that over 70% of researchers have failed to reproduce other scientist’s experiments [26].\nThe challenges in drug discovery and development for academics, research communities, and pharma industries needed for successful drug development can be broken down to cost, risk as well as pace.\n\n3.1. Cost and risk\nThe amount spent to develop an individual drug largely depends on the costs to conduct safety and efficacy studies and also to secure regulatory approvals. Estimates for the cost for Drug development range from ~ 1 billion to whopping 11.8 billion for a single drug [27,28]. However, around 90% of drugs in development for human use do not reach the market due to safety or efficacy concerns. Such failures can be due to lack of efficacy, safety issues, or a lack of funding to complete a trial [29]. In other cases, failing to maintain good manufacturing protocols and follow FDA guidance, as well as problems with patient recruitment, enrollment, retention and follow up can all compound to both complicate and increase the cost needed for drug development [29]. Given this mounting cost with little success due to high attrition rates, it is obvious that the drug development as a business model is very risky purely from an economical and financial sense. Aside from the high cost/high attrition rates nature of the drug discovery process, other drugs, like antibiotics or orphan drugs, are often abandoned and don’t reach the market due to little or no commercial interest [30].\n\n3.2. Pace\nThe process of drug research and development is extremely slow taking at least 7 to 10 years for a lead candidate to reach the marketplace [28]. This is mainly due to the rigorous process needed to ensure safety and efficacy through clinical human trial and as well as obtaining regulatory approvals. Duplication and reproducibility are other factors that also contributes to the slow pace of drug discovery. While duplication and reproducibility can be seen as a squander of time and resources, they remain essential to provide more data and evidence and ensure the safety and efficiency before they are prescribed to the population. The devastating malformations of children born to women prescribed ‘Thalidomide’, to treat morning sickness is a stark reminder of the important of independent rigorous evaluation of a drug’s safety profile before its release for population [31]. A more recent example, hydroxychloroquine as a treatment for COVID-19, highlights the importance of multiple and independent studies needed to demonstrate a drug’s safety and efficiency [32]. Other factors include, suboptimal collaboration or lack of meaningful collaborative efforts among academia, industry, and government institutions despite several effort to encourage collaboration [33]. This have led, on many instances, to academics and pharma sectors working on similar ideas in parallel, in secret, and often in competition. Therefore, the establishment of a trusted and fair framework of collaboration and data sharing can both speed up the pace and improve the outcome of successful drugs.\n\n3.2. Limitations and more of the same\nA large number of drugs approved by the FDA in the past 10 years are new formulations of existing drugs referred to as ‘me too drugs’. While in some cases these drugs have offered some improvements over older versions, in many cases improvements remain marginal with slight changes in side effects or activity profiles [34]. Since these drugs have identical mechanism of action to older versions their innovative value and overall benefit is oftentimes insignificant [35]. Additionally, the molecular effects of several marketed drugs remain unknown despite their proven effectiveness. For example, acetaminophen is used by millions to treat mild to moderate pain while lithium is a first-line treatment for biopolar disorder. Yet the exact molecular target and mechanism of action remain unknown [36,37]. Many diseases particularly those affect the nervous system like Alzheimer, Parkinson’s, and depression lack accurate biomarkers [38,39]. While progress is being made, the lack of reliable biomarkers remains another impediment for the accurate diagnosis, prognosis and effective drug development against these diseases."}