Saturday, April 18, 2020

Some clarity in murky waters

With lockdowns and death of social life, I have taken to Twitter to vent off my frustration with the way the British government has been handling the Covid-19 pandemic. But, as my screen time increased so did my frustration with the amount of misinformation that it out there on many scientific questions and one of these is how the drug development process works. So, I see it fitting to shed some light on how the sometimes very precious medicines make their way to you. 
The drug development industry is one of the most if not the most regulated industry in the world, all aspects of drug development from the conception of the molecule in the laboratory to the day the last patient in any clinical trial has taken the medicine have to be documented, inspected, reviewed and contested before any medicine gets the green light to be marketed and then make its way to the patient. The reason this industry is heavily regulated is due to some disasters that happened in the past from the Nuremberg trials where Nazi doctors were conducting human experiments on concentration camp prisoners to the Thalidomide scandal to name just a few. 
The first step in the development for novel therapeutic molecules is to make sure they show efficacy which is another way of saying that they have the potential to treat an ailment. This is usually done in vitro, if there is a glimpse of evidence that the molecule has a beneficial effect, animal studies can be the next step in the process. These studies will have to be conducted according to guidelines, and the safety of the product has to be assessed in these models. For some indications, there exist animals exhibiting symptoms of the studied condition but these are not available for all indications. Experimentation on animal models is conducted by utilizing multiple concentrations and multiple dosings of the product under investigation. If the animal data show that the product has the potential to be well-tolerated, then the move to clinical trials can be considered. 
The move to the clinical phase of the development is when regulatory agencies such as the FDA which act as the police of the pharma industry start getting involved. For large companies with extensive development experience, the move can be smooth as they have an army of staff with all expertise required. For smaller companies, regulatory agencies tend to take them by the hand offering them incentives, reduced fees and scientific advice. The latter procedure is when the company has a set of questions on the drug development process that they would like to discuss and get validated and through this procedure they can tap into the expertise offered by regulatory agencies around the world. It is of note that most if not all sovereign countries around the world have regulatory agencies. The G7 countries have the largest and most experienced staff but countries rich and poor have committees in place to study and decide whether to approve procedures based on the evidence presented in documents submitted by pharma companies. 
For any company to start a clinical trial, a dossier needs to be compiled this is called the clinical trial application. In this application the drug developer needs to have the protocol that is like a manual to be followed by investigators (clinicians) and staff at the sites where the clinical trial will be taking place in addition to other technical documents detailing the efficacy and quality  and  safety tests that have been conducted to show that the product is fairly safe to proceed to usage in humans. 
Phase I trial is the first-in man, this is the riskiest of all phases for participants, and it usually is conducted on healthy volunteers unless it is unethical to do so (e.g. drugs known to have serious side effects that a healthy patient should not be exposed to). This phase usually focuses on showing safety and involves a small number of volunteers. The drug developer needs an approval from each nation where the trial takes place. This comes after studying the dossier submitted and getting an ethics committee involved to approve the trial. Ethics committees look at whether the way the study is designed ensures the safety and integrity of trial subjects. They have doctors, lawyers, as well as patients in these committees.  Not many nations allow phase I trials to be conducted on their people but countries in the EU, as well as the US and Canada and South Korea do allow phase I trials because they can monitor patients in case of serious incidents following the administration of the drug. 
If all goes well, then the drug developer can move to phase 2, which is a larger trial where both efficacy (proof of concept) and safety are assessed. Some phase 2 trials are used to identify the best dose (safest and most efficacious). These trials are usually multi-center conducted in several countries around the world. An approval needs to be received for this phase from each regulatory agency in each country where the trial is conducted.
If phase 2 trials show evidence that the drug under investigation has the potential to show some efficacy in a larger population then the move goes to phase 3. This phase is a decisive phase in dug development. A huge proportion of trials do not make it past phase 2, but once phase 3 starts, there is a lot at stakes. The trial in this phase are usually designed to show efficacy either in comparison to a placebo (rare these days) or another drug that is thought to be not do good and is already in use by doctors. Phase 3 trials can include even 40-50 countries, with multiple sites in each country. The same process of approval is needed as in phase I and 2, but at this stage, more animal and human data is available and drug developers are scrutinized more by the regulators. Approvals can take months to be handed to them by regulators. 
In general, trials can take from 1 to 4 or 6 years, and the length varies depending on the indication to be treated, the prevalence of the disease and the speed of recruiting the patients. Rare diseases are very hard to recruit for and trials for these would only include 10-20 patients sometimes. 
If all goes well, and it seldom does, the drug developer now has data from phase 3 trials to suggest that the drug is efficacious and superior to either placebo or standard of care. To show this the trial would have been designed to include enough patients (powered) to show that any difference between the treatment group and the placebo group could not be due to chance or in other words proving that the null hypothesis in wrong. 
During the clinical trials, the drug developer would have started to has to prepare a marketing authorization application. In this application all the details of the development need to be documented. This is a colossal dossier especially if the drug is a novel molecule. The experts in the agency make sure that all the guidance laid out by the regulators (e.g. FDA and EMA) have been followed and that the quality of the product is ensured as well as safety and the claimed efficacy can be verified. Questions are asked by regulators at every step of the process, and every regulatory agency can have its own questions that need to be answered in a timely manner with very tight deadlines.
If the evidence to suggest that the drug under investigation has a favorable benefit/risk profile i.e. the benefits from taking the drug to treat an indication outweigh the potential risks associated with it, the drug receives a marketing authorization or a license and can be marketed. However, it does not all stop here, pricing and reimbursement have to then be negotiated with governments around the world before the product can be placed on the market. 
The whole process takes years and years, but for serious diseases like cancer, the process can be sped up as there is a potential for accelerated reviews if drug has the potential to save lives  as is the case with Covid-19. 

Thursday, April 9, 2020

The good, the bad and the ugly

As humanity finds itself in unchartered waters trying to steer away from an invisible enemy, our interconnectedness as human beings has never been more apparent. We are living at a time when a pandemic is sweeping across the planet at unprecedented pace, reshaping the post-modern world as we know it. The incubation period of many viruses which would have elapsed during travel in the olden days seems to be long enough now for these to cross continents in a matter of days. The speed of travel and the pace of life that we have become accustomed to is now coming back to haunt us.

This virus is not a great leveller, those who are considered to be at the bottom of the heap by society are paying a high price during this pandemic. Reports are showing us that wealth and privilege play a great part on deciding who lives and who dies. As I see this pandemic emphasising the inequality of societies around the world, I cannot help but draw parallels with scenes from the epic movie Titanic. First class passengers being the first to evade the sinking ship with guaranteed comfort whilst the lower classes are left to perish in the cold waters.

This pandemic has brought out the worst in people; we are seeing how companies are profiteering in trading with people’s lives by hiking prices of essential life-saving equipment, how air piracy has become a norm with world leaders literally stealing medical equipment destined for others, and how the blaming fingers of politicians are trying to find a scapegoat to divert attention away from their utter failures in dealing with the crisis.

Amidst all this heinousness, the planet is now breathing, neighbours are talking to each, families are getting to know each other and society is already thinking how to make the world a fairer place where the next pandemic will be easier to handle.   

Thursday, April 11, 2019

Beauty and The Beast

In 2008, when the world’s eyes were turned to a new kid in the block, giving a victory speech in one of the most historic passings of power in recent history, thousands of miles away, another history was being made. The president of Algeria was to change the constitution to allow himself to stay “with” the presidency until death do them part. 

When Bouteflika was brought in by the army in 1999, Algeria was trying to turn the page on one of the most difficult and darkest chapters in its history. A decade of blood and terror where the struggle to survive and the fear of facing death was the daily routine of all Algerians. A few years into his rule, peace-in the form of decrease in the number of massacres-started to crawl back into our lives; daily news of death was not the norm anymore, and life started to go back to normality, except that everything had changed, and society was never to be the same again. Suspicion of the other meant that people started to withdraw into self-inflicted confinements, and apathy started to reign. Public space was confiscated from Algerians by the regime in place and the ghost of the black decade was always hovering around to deter people from any attempt of change. The people had divorced their country, their regime and each other.

With all this apathy, a new beast was growing, fuelled by soaring oil prices, the appalling management of public money meant that anything was up for grabs. Algeria was the new Eldorado where anyone who wanted to make a quick buck would go to. The regime running the country continued to deteriorate and became a mafia in all sense of the word, and as the oil prices started to plummet, the mafia had to find new ways to satisfy its insatiable appetite for money, this meant that illegal trading, money laundering and drug dealing was also on the table; the mafia was pushing the country into a dystopia.

My family like many other families had to think of ways to survive in a country under regime that cared for no one and where everyone was for themselves. Water supplied by the government is not trusted for consumption so my dad started a weekly trip to a spring to fill jerrycans with clean water to use for cooking and for drinking as bottled water would not be sufficient. Meat was sourced directly from farms as my sister, an inspector of food quality warned of the dangers of meat consumption, hospitals were to be avoided at all cost as my sister who is a doctor warned against these. Our cities became open air prisons, and got uglier by the day, so trips to the countryside were our escape from small living spaces and eyesores mushrooming like there is no tomorrow.  

As the beast grew bigger, it engulfed every corner of the country and every fabric of society, very few were those who resisted the regime and its practices. But as history has it, against the backdrop of all this chaos, a new beautiful generation which saw the pain, the chaos, and the injustice, and witnessed on a daily basis the further descent of the country into an abyss was waiting for the right moment; it seized it in the most beautiful way , it broke the silence and lifted the fear and the rest is very recent history.

Thursday, November 23, 2017

Back in Blighty

"You must be mad!”. This is how friends and family  greeted my decision to return to England after leaving it some years ago. Four cities and three countries later, I find myself in the town that I used to love so very much, but which I had to leave for greener pastures.
I do question my sanity when I look out of the window and cannot tell whether it is morning or afternoon because of the constant dark aura that wraps this country in the autumn months, or when I look at the sky and the dreary greyness is all I can see. I sometimes wonder if it was the right decision when I think of all the taxes we pay and how childcare fees make you think that you get punished for having children in this country.
I left England because I was lonely, I wanted to be close to family. London was great, it offered me everything I dreamed of as a youngster, yet hitting the age of 30 and having no kids and no family around me made me unhappy.  I convinced my husband that brining up kids in a good area of London without having a million pounds stashed away was going to be impossible. I could not see myself continuing to take the tube or public transport beyond the age of 30 or as a pregnant lady, inhaling all the horrible black dust on the underground…  Aside from the vibrant atmosphere of the city and the illusion that you are somewhat important just because you happen to wear a suit and take a boat to a business meeting, there was nothing to keep us in London, so move away we did.
When I left, I wanted to be somewhere that offered me everything; the family, the children, the sun, and the money. Above all, I wanted a new beginning. Fast forward a few years, my decision, which was great for my social life did not seem to do much for my career. My freelance business never really took off and I had enough of sponging off my husband. So after a few years of dwindling income, I decided it was time to head back to England  to spend more years working in a box, looking at a box and dealing with people who cannot think outside the box, aka the corporate world. Now that I am back, I sit in front of a box all day making sure I clock up enough years, serving my corporate sentence so that I can be free again. For a rebel like me, every day is an agony mostly because of the red tape that exists everywhere. People follow procedures blindly and seem to leave their common sense and brain at home before heading for work. What the business world calls streamlining, I label dumbing down and automating tasks so that work becomes merely a robotic repetitive mechanism. Sitting at your desk wishing your life away until the weekend is what I do. But the weekend is not a time for fun anymore.
We left as 2 and now we are 4. Life with young children is very different; nothing prepares you for it. What seemed like a given before is now a luxury-at least in this country. Life for middle class families here is hard. Finding Alibaba’s treasure cave is easier than finding decent childcare. Nurseries are run by half-wits who cannot even spell and who hate looking after children;  but they ask for astronomical amounts of money.
As parents, we run from school to nursery (which are never near each other) to after school activities to nowhere. The weekends are spent trying to entertain the kids or get ready for a new school week. Nannies and babysitters are so fussy that you think they are doing it for free. As a result, your social life as an adult away from the kids becomes non-existent
In all this chaos, you find pleasure in knowing that your kid attends an outstanding school and seeing them thrive there makes all the agony worthwhile. The school becomes your life again as a parent, and your kid performing a song or a play during a school assembly warms your heart.

Tuesday, October 6, 2015

How green is your grass?

We are told that the grass is greener where we are not. Just like the color of the sea which gets bluer the further away you move from the shores, the grass seems greener the further away you drift from your home.
Undeterred by Dahmane Elharrachi’s song  and the tales of those older than us who tell us that leaving one’s  home is not for the faint-hearted, we embark on a journey of discovery and adventure,  leaving everything familiar behind. We follow our dreams, which we later realize they are not even ours. We taste the different flavors of each land and we keep moving in search of that perfect place to finally realize that it only exists in our hearts.
Some wise people exercise discipline and convince themselves that whatever they have is perfect and that the only way to be content is to accept what is there, deal with it and improve it. This is the case of those Algerians who enjoy their life back home. The case is also true for citizens of other countries who never complain about the bad weather, the high taxes or the dirty and polluted cities. They will just live in their little town or big city never yearning to know what if feels like to be somewhere else.
I came across people on my various trips who are just like me, they have lived in various countries, and are always willing to move, this gives me reassurance. But, I have also met people who stayed in one place all their lives, and worked at the same company for as long as they have been employed; life abroad does not tempt them in the slightest. These people have travelled but they have always come home. I feel jealous of them sometimes. They have found satisfaction, and are confident that the land where they are offers just as much as anywhere else.
Along my trips, I met so many people each with their own story of leaving their land. For some, it is the search of freedom. A roommate of mine in college told me once that she could never imagine herself wearing a bikini in England (on a hot day), but she would gladly do it in Egypt because there she feels free(er). Many other expats also re-iterate the same feeling of being free,  away from the eyes of those who have come to know them very well; as if ones’ homeland becomes a confinement and freedom is only to be found away, anywhere but at home. For those of us who come from conservative societies, we think that our society is suffocating because of customs, and religion; we flee to get away but even those from the free world seem to be fleeing. Some flee taxes, others flee the cold weather, for others it is just the experience to put in a CV to get promoted and earn more money. For a few, it is the love of adventure.
Beacuse you have lived in multiple lands, people think that you are an authority on the best places to live; I personally think that there is no perfect land but that which exists in your heart and that the grass is as green as your eyes make you see it. If one’s heart is content and happy, it will always be happy no matter where it lives, and if you are miserable grumpy soul, you’ll always find faults with every country that you have called home. I belong to the latter category I am afraid.

Thursday, July 9, 2015

Ramdhan Z'man

As someone living in nostalgia, I keep trying to convince myself that many things used to be better before. One of them is Ramadhan. As a kid, I used to get so excited about this month and await its arrival with great anticipation; for me, it meant eating more sweets, and being able to play outside when it is dark.

One of the things I miss dearly these days is the smell of Ramadhan and the aura that accompanied this month. You could not escape it,  it was in the air everywhere; it was not just the smell of coriander in shorba emanating from every house in the neighborhood, not the smell of Z’labia being deep fried or dipped in syrup, not that of Qalbellouz sold in stalls in many places, and not that of orange flower water in the Sherbet. It was all of that and a lot more. Even if you were too young to fast, or were at school where you would not whiff any of the above delightful smells, you could still feel the presence of the month.

As I grow wiser, I feel that aura less and less and start to believe that it was maybe one of those childish feelings I had, which rendered my world a lot more exciting. Sometimes, I wish I could reconstruct the atmosphere in my head for it is a great one. I travel to Algeria in Ramadhan sometimes hoping to experience that feel again but it is not there anymore. All you experience is the heat and the dead streets. I think that people have just given up on trying to make this month exciting.

People complain a lot about this month, I do, sometimes, as well. We find the fast difficult, and I find the cooking difficult. We are expected to fast, pray, be spiritual, and cook decent food without tasting it. If there is an invitee, we pray that the salt is just right.

In all of the extra tasks we create during this month, we distract ourselves from the true essence of this month, and as Ramadhan nears its end, we feel a sort of regret for having complained about its arrival, for not welcoming it warmly enough, for not having done enough good deeds and wonder what our lives will be like next Ramadhan, and whether the aura will visit us again. 

Sunday, May 25, 2014

Mrs La Blanche

Mr Le Blanc, according to Gad Elmaleh, is this guy whom the universe conspires to make his life as smooth as silk. When he eats all the components in his sandwich enter into a pact and decide to do their best to make it to his mouth without soiling his nice clean clothes. Eating a sandwich for him is a pleasure, no mayo, no sauce leaves that sandwich until it reaches the desired destination. At the airport, his luggage is the first to arrive on the belt, intact and spotless; and the list of fortunate events in his life is endless. At the other end of the spectrum there is Mr. Swad essa3d, whom Murphy’s law shapes his life and everything he does goes awry.

For every Mr. Le Blanc, there is of course Mrs La Blanche. You spot her at the local coffee shop drinking a skinny latte, looking like a million dollars. She has three kids, not one, not two but three! Yet she manages to have a figure of a single woman in her teens. She has three kids and she manages to have hair that looks like she has just stepped out of a salon. No dark circles under the eyes; so her kids must have slept through the night from day zero.

Mrs La Blanche’s kids sit quietly when she eating out with hubby, playing with their toys; eating all their veggies and any crap that Mrs La Blanche offers. She of course manages to stay as fresh looking as when she stepped out of her house. Her kids do not seem to grab her hair or clothes. The kids smile or laugh all the time, you wonder if they were born in Stepfod town. You look at what she is having and you want to ask the waiter to get you exactly the same stuffs maybe some of that luck would rub on you.

She drives a Range Rover to drop her kids at school or at nursery. She wears a different outfit everyday, which looks like it has just arrived from the drycleaners. Her kids put a kiss on her cheek and say bye and run to their classroom looking like they are going to a playground. At nursery, she leaves her baby who has such a big smile on his face, you wonder if he on something. Everyday you see Mrs La Blanche, you hate her more; you try to convince yourself that she has at least two maids and three nannies for she sets the standards so high you wonder if she is human.

You, on the other hand, never sleep through the night, because your baby does not; so looking fresh is out of the question. Your barely have time to comb your hair because your baby is screaming for something that is not among the 1000 things in front of her. You decide to wear hat nice outfit to outdo Mrs La Blanche just that once but on the way to the car, the baby decides to puke all over you and you run back to the house and grab that dress that does not need ironing but which makes look like Jo Brand. You decide to wear it anyway because you are so late for everything. You run around the house like crazy checking and rechecking that you have got the million things that you baby does not need at nursery, but which you decide to pack anyway because you want to make your life more stressful.

At nursery, your baby screams and screams when you leave her that you decide to either be the first or last to arrive at the nursery so that you can make it out quietly and avoid the accusing eyes of  those mums looking at you like it is your fault that your baby does not want to leave your side. There is nothing worse than judging eyes of other mums who want to tell you how to bring up your child.

When you have had enough and you want to eat out with hubby, you pray and pray that your baby does not make a scene; she of course does not let you eat and you end up taking turns with your husband on eating and drinking. She barely eats her food, and ends up being grumpy as she can see all the people around her eating and she cannot do the same. Your baby decides all of a sudden that bedtime that night is when the dessert arrives. You ask the waiter to pack it for you and make your way back home.

As a mum, you want to be Mrs La Blanche everyday, you tire yourself like mad to get there; but then you realize that she is 10 years younger than you, she started having kids when you were busy climbing the career ladder. She married a loaded Mr. right, and after all her kids go to school, she can start her career and will become a CEO by the time she is 45. You give up trying...

Some clarity in murky waters

With lockdowns and death of social life, I have taken to Twitter to vent off my frustration with the way the British government has been ...